Identification

Name
Topotecan
Accession Number
DB01030  (APRD00687)
Type
Small Molecule
Groups
Approved, Investigational
Description

An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerases, type I. [PubChem]

Structure
Thumb
Synonyms
  • 9-[(dimethylamino)Methyl]-10-hydroxy-(4S)-camptothecin
  • Topotecan
  • Topotecane
  • Topotecanum
External IDs
SKF-104864
Product Ingredients
IngredientUNIICASInChI Key
Topotecan hydrochloride956S425ZCY119413-54-6DGHHQBMTXTWTJV-BQAIUKQQSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act TopotecanPowder, for solution4 mgIntravenousActavis Pharma Company2015-11-17Not applicableCanada
Act TopotecanPowder, for solution1 mgIntravenousActavis Pharma CompanyNot applicableNot applicableCanada
HycamtinInjection, powder, for solution1 mgIntravenousNovartis Europharm Limited1996-11-12Not applicableEu
HycamtinInjection, powder, lyophilized, for solution4 mg/4mLIntravenousGlaxosmithkline Inc1996-06-072018-07-31Us
HycamtinCapsule.25 mg/1OralNovartis Pharmaceuticals Corporation2017-07-07Not applicableUs
HycamtinInjection, powder, lyophilized, for solution4 mg/4mLIntravenousNovartis Pharmaceuticals Corporation2016-12-21Not applicableUs
HycamtinCapsule1 mgOralNovartis Europharm Limited1996-11-12Not applicableEu
HycamtinCapsule0.25 mg/1OralGlaxoSmithKline Manufacturing SpA2008-09-162017-12-13Us
HycamtinInjection, powder, for solution4 mgIntravenousNovartis Europharm Limited1996-11-12Not applicableEu
HycamtinCapsule0.25 mg/1OralGlaxosmithkline Inc2008-09-162017-12-31Us00007 4205 11 nlmimage10 1c198e1c
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mylan-topotecan Hydrochloride for InjectionPowder, for solution4 mgIntravenousMylan PharmaceuticalsNot applicableNot applicableCanada
PMS-topotecanPowder, for solution4 mgIntravenousPharmascience Inc2013-08-29Not applicableCanada
PMS-topotecanPowder, for solution1 mgIntravenousPharmascience IncNot applicableNot applicableCanada
PotactasolInjection, powder, for solution1 mgIntravenousActavis Group Ptc Ehf.2011-01-06Not applicableEu
PotactasolInjection, powder, for solution4 mgIntravenousActavis Group Ptc Ehf.2011-01-06Not applicableEu
TopotecanInjection, powder, lyophilized, for solution4 mg/4mLIntravenousIngenus Pharmaceuticals Llc2016-12-07Not applicableUs
TopotecanInjection, solution, concentrate1 mg/1mLIntravenousMylan Institutional2018-04-09Not applicableUs
Topotecan ActavisInjection, powder, for solution1 mgIntravenousActavis Group Ptc Ehf.2009-07-24Not applicableEu
Topotecan ActavisInjection, powder, for solution1 mgIntravenousActavis Group Ptc Ehf.2009-07-24Not applicableEu
Topotecan ActavisInjection, powder, for solution4 mgIntravenousActavis Group Ptc Ehf.2009-07-24Not applicableEu
Categories
UNII
7M7YKX2N15
CAS number
123948-87-8
Weight
Average: 421.4458
Monoisotopic: 421.163770861
Chemical Formula
C23H23N3O5
InChI Key
UCFGDBYHRUNTLO-QHCPKHFHSA-N
InChI
InChI=1S/C23H23N3O5/c1-4-23(30)16-8-18-20-12(9-26(18)21(28)15(16)11-31-22(23)29)7-13-14(10-25(2)3)19(27)6-5-17(13)24-20/h5-8,27,30H,4,9-11H2,1-3H3/t23-/m0/s1
IUPAC Name
(19S)-8-[(dimethylamino)methyl]-19-ethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.0²,¹¹.0⁴,⁹.0¹⁵,²⁰]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione
SMILES
CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=C(C=CC(O)=C4CN(C)C)N=C13)C2=O

Pharmacology

Indication

For the treatment of advanced ovarian cancer in patients with disease that has recurred or progressed following therapy with platinum-based regimens. Also used as a second-line therapy for treatment-sensitive small cell lung cancer, as well as in combination with cisplatin for the treatment of stage IV-B, recurrent, or persistent cervical cancer not amenable to curative treatment with surgery and/or radiation therapy.

Associated Conditions
Pharmacodynamics

Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from the Camptotheca acuminata tree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. DNA topoisomerases are enzymes in the cell nucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug.

Mechanism of action

Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death).

Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (−1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, Topotecan acts as an uncompetitive inhibitor.

TargetActionsOrganism
ADNA topoisomerase 1
inhibitor
Human
UDNA topoisomerase I, mitochondrial
inhibitor
Human
ADNA
intercalation
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

35%

Metabolism

Topotecan undergoes a reversible pH dependent hydrolysis of its lactone moiety; it is the lactone form that is pharmacologically active.

Route of elimination

Renal clearance is an important determinant of topotecan elimination. In a mass balance/excretion study in 4 patients with solid tumors, the overall recovery of total topotecan and its N-desmethyl metabolite in urine and feces over 9 days averaged 73.4 ± 2.3% of the administered IV dose. Fecal elimination of total topotecan accounted for 9 ± 3.6% while fecal elimination of N-desmethyl topotecan was 1.7 ± 0.6%.

Half life

2-3 hours

Clearance
Not Available
Toxicity

The primary anticipated complication of overdosage would consist of bone marrow suppression.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Topotecan.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Topotecan.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Topotecan is combined with 2-Methoxyethanol.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Topotecan.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Topotecan.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Topotecan.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Topotecan.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Topotecan is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be increased when combined with Topotecan.
AbacavirTopotecan may decrease the excretion rate of Abacavir which could result in a higher serum level.
Food Interactions
Not Available

References

Synthesis Reference

Venkata Raghavendra Palle, Sekhar Nariyam, Lankeshwara Matti, "PROCESS FOR PREPARING TOPOTECAN." U.S. Patent US20070149783, issued June 28, 2007.

US20070149783
General References
  1. Kollmannsberger C, Mross K, Jakob A, Kanz L, Bokemeyer C: Topotecan - A novel topoisomerase I inhibitor: pharmacology and clinical experience. Oncology. 1999;56(1):1-12. [PubMed:9885371]
  2. Herben VM, ten Bokkel Huinink WW, Beijnen JH: Clinical pharmacokinetics of topotecan. Clin Pharmacokinet. 1996 Aug;31(2):85-102. [PubMed:8853931]
  3. Dennis MJ, Beijnen JH, Grochow LB, van Warmerdam LJ: An overview of the clinical pharmacology of topotecan. Semin Oncol. 1997 Feb;24(1 Suppl 5):S5-12-S5-18. [PubMed:9122737]
External Links
Human Metabolome Database
HMDB0015164
KEGG Compound
C11158
PubChem Compound
60700
PubChem Substance
46505204
ChemSpider
54705
BindingDB
50034026
ChEBI
63632
ChEMBL
CHEMBL84
Therapeutic Targets Database
DAP000648
PharmGKB
PA451729
HET
TTC
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Topotecan
ATC Codes
L01XX17 — Topotecan
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
1k4t / 1rr8 / 1rrj
FDA label
Download (78.6 KB)
MSDS
Download (29.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentMalignant Gliomas / WHO Grade III or IV Recurrent Glioma1
0RecruitingTreatmentGliomas1
0RecruitingTreatmentHigh Grade Glioma (HGG) / Neoplasms, Brain1
1Active Not RecruitingTreatmentAdult Acute Megakaryoblastic Leukemia / Adult Acute Monoblastic Leukemia / Adult Acute Monocytic Leukemia / Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With Maturation / Adult Acute Myeloid Leukemia With Minimal Differentiation / Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1 / Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1 / Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A / Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL / Adult Acute Myeloid Leukemia Without Maturation / Adult Acute Myelomonocytic Leukemia / Adult Erythroleukemia / Adult Pure Erythroid Leukemia / Chronic Myelomonocytic Leukemia / De Novo Myelodysplastic Syndrome / Essential Thrombocythemia (ET) / Hematopoietic and Lymphoid Cell Neoplasm / Myelodysplastic Syndrome / Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia / Polycythemia Vera (PV) / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Recurrent Disease / Secondary Myelodysplastic Syndromes1
1Active Not RecruitingTreatmentAdult Central Nervous System Germ Cell Tumor / Adult Rhabdomyosarcoma / Childhood Central Nervous System Germ Cell Tumor / Childhood Soft Tissue Sarcoma / Ewing's Sarcoma (ES) / Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Ovarian Mixed Germ Cell Tumor / Previously Untreated Childhood Rhabdomyosarcoma / Recurrent Adult Brain Tumor / Recurrent Adult Soft Tissue Sarcoma / Recurrent Childhood Brain Stem Glioma / Recurrent Childhood Cerebellar Astrocytoma / Recurrent Childhood Cerebral Astrocytoma / Recurrent Childhood Ependymoma / Recurrent Childhood Malignant Germ Cell Tumor / Recurrent Childhood Medulloblastoma / Recurrent Childhood Pineoblastoma / Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor / Recurrent Childhood Visual Pathway and Hypothalamic Glioma / Recurrent Childhood Visual Pathway Glioma / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Extragonadal Germ Cell Tumor / Recurrent Extragonadal Non-seminomatous Germ Cell Tumor / Recurrent Malignant Testicular Germ Cell Tumor / Recurrent Neuroblastoma / Recurrent Ovarian Germ Cell Tumor / Recurrent Wilms Tumor and Other Childhood Kidney Tumors / Tumors, Solid / Unspecified Adult Solid Tumor, Protocol Specific / Unspecified Childhood Solid Tumor, Protocol Specific1
1Active Not RecruitingTreatmentAdult Solid Neoplasm1
1Active Not RecruitingTreatmentCancer of the Ovary / Peritoneal Cavity Cancer1
1Active Not RecruitingTreatmentNeuroblastomas2
1Active Not RecruitingTreatmentRecurrent Childhood Anaplastic Large Cell Lymphoma / Recurrent Neuroblastoma / Unspecified Childhood Solid Tumor, Protocol Specific1
1Active Not RecruitingTreatmentRecurrent Small Cell Lung Carcinoma1
1CompletedScreeningTumors, Solid1
1CompletedSupportive CareLeptomeningeal Metastases1
1CompletedTreatmentAdvanced Solid Malignancies1
1CompletedTreatmentBrain and Central Nervous System Tumors2
1CompletedTreatmentBrenner Tumor / Ovarian Clear Cell Cystadenocarcinoma / Ovarian Endometrioid Adenocarcinoma / Ovarian Mixed Epithelial Carcinoma / Ovarian Mucinous Cystadenocarcinoma / Ovarian Serous Cystadenocarcinoma / Ovarian Undifferentiated Adenocarcinoma / Stage III Ovarian Epithelial Cancer / Stage IV Ovarian Epithelial Cancer1
1CompletedTreatmentCancer of the Ovary1
1CompletedTreatmentCancer of the Ovary / Carcinoma NOS / Fallopian Tube Cancer / Gynecological Malignancies / Malignancies / Metastases / Oncology / Tumors / Tumors, Solid1
1CompletedTreatmentCancer of the Ovary / Cervical Cancers / Endometrial Cancers / Fallopian Tube Cancer / Sarcomas / Vaginal Cancers / Vulvar Cancers1
1CompletedTreatmentCancer of the Ovary / Cervical Cancers / Endometrial Cancers / Lung Cancers1
1CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Peritoneal Cavity Cancer2
1CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer3
1CompletedTreatmentCancer of the Ovary / Primary Peritoneal Cavity Cancer2
1CompletedTreatmentCancer, Advanced1
1CompletedTreatmentCarcinoma, Small Cell / Lung Cancers1
1CompletedTreatmentCervical Cancers2
1CompletedTreatmentChildhood Solid Tumors / Malignant Solid Tumours1
1CompletedTreatmentChronic Myeloproliferative Disorders / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Precancerous Conditions / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentEndometrial Cancers1
1CompletedTreatmentEsophageal Cancers / Head and Neck Carcinoma / Lung Cancer Small Cell Lung Cancer (SCLC) / Malignant Neoplasm of Pancreas / Malignant Neoplasm of Stomach1
1CompletedTreatmentEsophageal Cancers / Lung Cancers / Malignant Lymphomas1
1CompletedTreatmentGenital Neoplasms, Female1
1CompletedTreatmentGynecologic Tumors1
1CompletedTreatmentLeukemias3
1CompletedTreatmentLeukemias / Malignant Lymphomas / Meningeal Neoplasms1
1CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
1CompletedTreatmentLeukemias / Neutropenias1
1CompletedTreatmentLung Cancer Small Cell Lung Cancer (SCLC) / Solid Tumor Cancers1
1CompletedTreatmentLung Cancer Small Cell Lung Cancer (SCLC) / Tumors1
1CompletedTreatmentLung Cancer Small Cell Lung Cancer (SCLC) / Tumors, Solid1
1CompletedTreatmentLung Cancers3
1CompletedTreatmentLung Cancers / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentMalignancies2
1CompletedTreatmentMalignancies / Solid Tumor Cancers1
1CompletedTreatmentMalignant Diseases1
1CompletedTreatmentMalignant Lymphomas / Small Intestine Cancer / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentMalignant Lymphomas / Tumors, Solid1
1CompletedTreatmentMalignant Solid Tumours1
1CompletedTreatmentMetastatic Solid Tumors1
1CompletedTreatmentMultiple Myeloma (MM) / Plasma Cell Neoplasms1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentNeoplasms Malignant / Refractory Tumors1
1CompletedTreatmentNeuroblastomas2
1CompletedTreatmentRectal Neoplasms1
1CompletedTreatmentRetinoblastoma1
1CompletedTreatmentTumors1
1CompletedTreatmentTumors, Solid2
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific5
1RecruitingTreatmentAdvanced Cancers1
1RecruitingTreatmentCancer of the Ovary1
1RecruitingTreatmentClear Cell Sarcoma of Soft Tissue / Ewing's Sarcoma (ES) / Germ Cell Tumors / Hepatoblastomas / Neuroblastomas / Non-rhabdomyosarcoma Soft Tissue Sarcomas / Renal Cell Adenocarcinoma / Retinoblastoma / Rhabdoid Tumors / Rhabdomyosarcomas / Sarcoma, Osteogenic / Wilms' tumor1
1RecruitingTreatmentGliomas1
1RecruitingTreatmentNeoplasms1
1RecruitingTreatmentNeuroblastomas1
1TerminatedTreatmentBrain and Central Nervous System Tumors / Carcinoma of Unknown Primary / Leukemias / Malignant Lymphomas / Unspecified Childhood Solid Tumor, Protocol Specific1
1TerminatedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Peritoneal Cavity Cancer1
1TerminatedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
1TerminatedTreatmentCancer of the Ovary / Relapses1
1TerminatedTreatmentCervix Cancer1
1TerminatedTreatmentRectal Carcinoma / Renal Cell Adenocarcinoma1
1TerminatedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1Unknown StatusTreatmentBrain and Central Nervous System Tumors1
1Unknown StatusTreatmentMalignancies1
1Unknown StatusTreatmentUnspecified Childhood Solid Tumor, Protocol Specific1
1, 2Active Not RecruitingTreatmentAbdominal wall neoplasm / Cancer of the Ovary / Fallopian Tube Cancer1
1, 2Active Not RecruitingTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
1, 2CompletedNot AvailableCancer of the Ovary1
1, 2CompletedTreatmentCancer of the Ovary4
1, 2CompletedTreatmentCervical Cancers1
1, 2CompletedTreatmentChronic Myeloproliferative Disorders / Leukemias / Myelodysplastic Syndromes / Thrombocytopenias1
1, 2CompletedTreatmentDrug/Agent Toxicity by Tissue/Organ / Lung Cancers / Radiation Toxicity1
1, 2CompletedTreatmentLeukemias1
1, 2CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
1, 2CompletedTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
1, 2CompletedTreatmentLung Cancers1
1, 2CompletedTreatmentMultiple Myeloma (MM)1
1, 2CompletedTreatmentTumors1
1, 2CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1, 2CompletedTreatmentRefractory Small cell lung cancer / Unspecified Adult Solid Tumor, Protocol Specific1
1, 2RecruitingTreatmentCancer of the Ovary / Lung Cancer Small Cell Lung Cancer (SCLC)1
1, 2RecruitingTreatmentCarcinoma, Non-Small -Cell Lung / Extrapulmonary Small Cell Cancer / Neoplasms, Ovarian / Neuroendocrine Carcinomas / Small Cell Lung Carcinoma / Uterine Cervical Neoplasms1
1, 2RecruitingTreatmentCarcinoma, Small Cell / Lung Cancer Small Cell Lung Cancer (SCLC) / Lung Cancers1
1, 2RecruitingTreatmentChildren, Adolescents and Young Adults With Refractory or Recurrent Malignancies1
1, 2RecruitingTreatmentTumors, Central Nervous System / Tumors, Solid1
1, 2SuspendedTreatmentAdult Solid Neoplasm / Metastatic Malignant Solid Neoplasm / Metastatic Solid Neoplasm / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma / Unresectable Solid Neoplasm1
1, 2TerminatedTreatmentCancer of the Ovary2
1, 2TerminatedTreatmentCervical Cancers1
1, 2TerminatedTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
1, 2TerminatedTreatmentNeoplasms, Brain / Tumors, Central Nervous System1
1, 2TerminatedTreatmentTumors, Solid1
1, 2Unknown StatusTreatmentBrain Neoplasms, Primary Malignant1
1, 2Unknown StatusTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
1, 2Unknown StatusTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1, 2WithdrawnTreatmentLarge Cell Neuroendocrine (NE) Tumors / Lung Cancer Small Cell Lung Cancer (SCLC) / Neuroendocrine (NE) Tumors1
2Active Not RecruitingTreatmentCentral Nervous System Neoplasms / Glioblastoma Multiforme (GBM) / Glioblastomas / Gliosarcoma / Neoplasms, Brain1
2Active Not RecruitingTreatmentGlioblastoma Multiforme (GBM) / Glioblastomas / Gliosarcoma / Malignant Gliomas1
2Active Not RecruitingTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
2Active Not RecruitingTreatmentLung Cancer Small Cell Lung Cancer (SCLC) / Small Cell Lung Cancer Extensive Stage / Small Cell Lung Cancer Limited Stage1
2CompletedNot AvailableLeukemias / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentAIDS-Related Diffuse Large Cell Lymphoma / AIDS-Related Diffuse Mixed Cell Lymphoma / AIDS-Related Diffuse Small Cleaved Cell Lymphoma / AIDS-related Immunoblastic Large Cell Lymphoma / AIDS-Related Lymphoblastic Lymphoma / AIDS-related Peripheral/Systemic Lymphoma / AIDS-related Primary CNS Lymphoma / AIDS-related Small Noncleaved Cell Lymphoma / Childhood Diffuse Large Cell Lymphoma / Childhood Immunoblastic Large Cell Lymphoma / HIV-associated Hodgkin Lymphoma / Leptomeningeal Metastases / Recurrent Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Myeloid Leukemia / Recurrent Childhood Large Cell Lymphoma / Recurrent Childhood Lymphoblastic Lymphoma / Recurrent Childhood Medulloblastoma / Recurrent Childhood Small Noncleaved Cell Lymphoma / Recurrent/Refractory Childhood Hodgkin Lymphoma / Unspecified Childhood Solid Tumor, Protocol Specific1
2CompletedTreatmentAdenocarcinoma of Colon / Adenocarcinoma of Rectum / Metastatic Disease1
2CompletedTreatmentAdenocarcinoma of the Cervix / Adenosquamous carcinoma of the cervix / Cervical Small Cell Carcinoma / Cervical Squamous Cell Carcinoma / Recurrent Cervical Carcinoma / Stage III Cervical Cancer / Stage IVA Cervical Cancer / Stage IVB Cervical Cancer1
2CompletedTreatmentAdult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Recurrent Adult Acute Myeloid Leukemia1
2CompletedTreatmentBrain and Central Nervous System Tumors2
2CompletedTreatmentBrain and Central Nervous System Tumors / Metastatic Cancers / Unspecified Adult Solid Tumor, Protocol Specific1
2CompletedTreatmentCancer of the Ovary6
2CompletedTreatmentCancer of the Ovary / Childhood Germ Cell Tumor / Extragonadal Germ Cell Tumor / Head and Neck Carcinoma / Liver Cancer / Malignant Lymphomas / Neuroblastomas / Renal Cancers / Retinoblastoma / Sarcomas / Testicular germ cell tumour1
2CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm1
2CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm / Neoplasms, Ovarian1
2CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Malignant Tumor of Peritoneum1
2CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Peritoneal Cavity Cancer2
2CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer3
2CompletedTreatmentCancer of the Ovary / Neoplasms, Ovarian1
2CompletedTreatmentCancer of the Ovary / Peritoneal Cavity Cancer1
2CompletedTreatmentCarcinoma of Unknown Primary / Lung Cancers1
2CompletedTreatmentCarcinoma, Small Cell1
2CompletedTreatmentCarcinoma, Small Cell / Lung Cancer Small Cell Lung Cancer (SCLC)1
2CompletedTreatmentCervical Cancers5
2CompletedTreatmentEndometrial Cancers / Neoplasms, Endometrial1
2CompletedTreatmentEwing Sarcoma of Bone / Extraosseous Ewing Sarcoma / Peripheral Primitive Neuroectodermal Tumor / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor1
2CompletedTreatmentEwing's Sarcoma (ES) / Neuroblastomas / Rhabdomyosarcomas1
2CompletedTreatmentExtensive Stage Small Cell Lung Cancer1
2CompletedTreatmentExtensive Stage Small Cell Lung Cancer / Refractory Small cell lung cancer2
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Progressive Multifocal Leukoencephalopathy1
2CompletedTreatmentLeukemias4
2CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
2CompletedTreatmentLeukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Diseases1
2CompletedTreatmentLung Cancer Small Cell Lung Cancer (SCLC)4
2CompletedTreatmentLung Cancers11
2CompletedTreatmentMalignant Lymphomas2
2CompletedTreatmentMalignant Neoplasm of Colon1
2CompletedTreatmentNeoplasms, Brain / Neuroblastomas / Tumors, Solid1
2CompletedTreatmentNeoplasms, Ovarian1
2CompletedTreatmentNeoplasms, Ovarian / Uterine Neoplasms1
2CompletedTreatmentNeuroblastomas3
2CompletedTreatmentNeuroblastomas / Sarcomas1
2CompletedTreatmentNeutropenias / Sarcomas1
2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentOvarian Epithelial Cancer1
2CompletedTreatmentOvarian Epithelial Cancer / Primary Peritoneal Cancer1
2CompletedTreatmentPlasma Cell Myeloma1
2CompletedTreatmentRecurrent Small Cell Lung Carcinoma1
2CompletedTreatmentRetinoblastoma1
2CompletedTreatmentSarcomas1
2CompletedTreatmentSoft Tissue Sarcoma (STS)1
2CompletedTreatmentTumors, Solid1
2Not Yet RecruitingTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
2Not Yet RecruitingTreatmentVery High Risk Neuroblastoma1
2RecruitingTreatmentAcute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome / Agnogenic Myeloid Metaplasia / Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative / Chronic Myelomonocytic Leukemia / Essential Thrombocythemia (ET) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic/Myeloproliferative Neoplasms / Polycythemia Vera (PV) / Recurrent Adult Acute Myeloid Leukemia / Refractory Acute Myeloid Leukemia1
2RecruitingTreatmentAdult Liposarcoma / Metastatic Bone Sarcomas / Metastatic Liposarcoma / Recurrent Adult Soft Tissue Sarcoma / Recurrent Liposarcoma / Recurrent Osteosarcoma / Stage IV Adult Soft Tissue Sarcoma1
2RecruitingTreatmentAtypical Teratoid Rhabdoid Tumors (ATRT) / Malignant Rhabdoid Tumors (MRT)1
2RecruitingTreatmentChildhood Atypical Teratoid/Rhabdoid Tumor / Embryonal Tumor With Abundant Neuropil and True Rosettes / Metastatic Malignant Neoplasm to the Leptomeninges / Recurrent Childhood Ependymoma / Recurrent Childhood Medulloblastoma1
2RecruitingTreatmentEndometrial Clear Cell Carcinoma / Ovarian Clear Cell Carcinoma1
2RecruitingTreatmentFallopian Tube Transitional Cell Carcinoma / Malignant Ovarian Clear Cell Tumor / Malignant Ovarian Endometrioid Tumor / Malignant Ovarian Mixed Epithelial Tumor / Malignant Ovarian Serous Tumor / Ovarian Seromucinous Carcinoma / Ovarian Transitional Cell Carcinoma / Primary Peritoneal Serous Adenocarcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma / Undifferentiated Fallopian Tube Carcinoma / Undifferentiated Ovarian Carcinoma1
2RecruitingTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
2RecruitingTreatmentMedulloblastomas / Neuroblastomas1
2RecruitingTreatmentMetastatic Small Cell Lung Cancer1
2RecruitingTreatmentNeuroblastomas2
2RecruitingTreatmentRecurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2RecruitingTreatmentRetinoblastoma1
2TerminatedTreatmentCancer of the Ovary2
2TerminatedTreatmentCancer of the Ovary / Primary Peritoneal Cavity Cancer1
2TerminatedTreatmentCancer, Breast1
2TerminatedTreatmentEpithelial Ovarian Carcinoma1
2TerminatedTreatmentExtensive Stage Small Cell Lung Cancer / Refractory Small cell lung cancer1
2TerminatedTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
2TerminatedTreatmentLung Cancers1
2TerminatedTreatmentCancer treatment / Malignancies / Ovarian / Relapses1
2TerminatedTreatmentMalignant Ovarian Endometrioid Tumor / Malignant Ovarian Serous Tumor / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2TerminatedTreatmentMalignant Ovarian Mixed Epithelial Tumor / Ovarian Clear Cell Cystadenocarcinoma / Ovarian Endometrioid Adenocarcinoma / Ovarian Mucinous Cystadenocarcinoma / Ovarian Serous Cystadenocarcinoma / Primary Peritoneal Carcinoma / Stage III Ovarian Cancer / Undifferentiated Ovarian Carcinoma1
2TerminatedTreatmentMediastinal Neoplasms1
2TerminatedTreatmentNeoplasms, Breast1
2TerminatedTreatmentNeuroblastomas1
2TerminatedTreatmentRecurrent Ovarian Epithelial Cancer1
2TerminatedTreatmentSarcomas1
2Unknown StatusTreatmentCancer of the Ovary1
2Unknown StatusTreatmentCentral Nervous System (CNS) Metastases / Metastatic Brain Tumors1
2Unknown StatusTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2Unknown StatusTreatmentLeukemias / Myelodysplastic Syndromes1
2Unknown StatusTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
2Unknown StatusTreatmentLung Cancers / Refractory to Chemotherapy1
2Unknown StatusTreatmentNeoplasms, Brain1
2Unknown StatusTreatmentNeuroblastomas1
2WithdrawnTreatmentCervical Cancers1
2WithdrawnTreatmentLung Cancers1
2WithdrawnTreatmentNeuroblastomas1
2WithdrawnTreatmentProstate Cancer1
2, 3Active Not RecruitingTreatmentLow Grade Ovarian Serous Adenocarcinoma / Micropapillary Serous Carcinoma / Ovarian Serous Adenocarcinoma / Primary Peritoneal Serous Adenocarcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2, 3RecruitingTreatmentLung Cancer Small Cell Lung Cancer (SCLC)2
2, 3SuspendedTreatmentDeleterious BRCA1 Gene Mutation / Deleterious BRCA2 Gene Mutation / Fallopian Tube Clear Cell Adenocarcinoma / Fallopian Tube Endometrioid Adenocarcinoma / Fallopian Tube Mucinous Adenocarcinoma / Fallopian Tube Serous Adenocarcinoma / Fallopian Tube Transitional Cell Carcinoma / Fallopian Tube Undifferentiated Carcinoma / Malignant Ovarian Mixed Epithelial Tumor / Ovarian Clear Cell Adenocarcinoma / Ovarian Endometrioid Adenocarcinoma / Ovarian Mucinous Adenocarcinoma / Ovarian Seromucinous Carcinoma / Ovarian Serous Adenocarcinoma / Ovarian Transitional Cell Carcinoma / Ovarian Undifferentiated Carcinoma / Primary Peritoneal Serous Adenocarcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma / Undifferentiated Fallopian Tube Carcinoma / Undifferentiated Ovarian Carcinoma1
3Active Not RecruitingTreatmentAdult Supratentorial Primitive Neuroectodermal Tumor (PNET) / Childhood Supratentorial Primitive Neuroectodermal Tumor / Ewing Sarcoma of Bone / Extraosseous Ewing Sarcoma / Extraosseous Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Non-Metastatic Extraskeletal Ewing Sarcoma / Peripheral Primitive Neuroectodermal Tumor of Bone / Peripheral Primitive Neuroectodermal Tumor of Soft Tissues / Peripheral Primitive Neuroectodermal Tumor of the Kidney / Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor1
3Active Not RecruitingTreatmentCancer of the Ovary1
3Active Not RecruitingTreatmentCancer of the Ovary / Fallopian Tube Cancer / Ovarian Epithelial Cancer / Primary Fallopian Tube Cancer / Primary Peritoneal Carcinoma1
3Active Not RecruitingTreatmentLocalized Resectable Neuroblastoma / Localized Unresectable Neuroblastoma / Recurrent Neuroblastoma / Regional Neuroblastoma / Stage 4 Neuroblastoma / Stage 4S Neuroblastoma1
3Active Not RecruitingTreatmentLung Cancer Small Cell Lung Cancer (SCLC)2
3Active Not RecruitingTreatmentLung Cancers1
3Active Not RecruitingTreatmentRetinal Neoplasms / Retinoblastoma1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3CompletedTreatmentAdenocarcinoma of the Cervix / Adenosquamous carcinoma of the cervix / Cervical Squamous Cell Carcinoma / Recurrent Cervical Carcinoma / Stage IVB Cervical Cancer2
3CompletedTreatmentAdult Malignant Mesenchymoma / Adult Rhabdomyosarcoma / Alveolar Childhood Rhabdomyosarcoma / Childhood Malignant Mesenchymoma / Embryonal Childhood Rhabdomyosarcoma / Embryonal-botryoid Childhood Rhabdomyosarcoma / Nonmetastatic Childhood Soft Tissue Sarcoma / Previously Untreated Childhood Rhabdomyosarcoma / Stage I Adult Soft Tissue Sarcoma / Stage II Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma1
3CompletedTreatmentCancer of the Ovary7
3CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer1
3CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Peritoneal Cavity Cancer1
3CompletedTreatmentCervical Cancers1
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
3CompletedTreatmentLung Cancer Small Cell Lung Cancer (SCLC)4
3CompletedTreatmentLung Cancers2
3CompletedTreatmentNeoplasms, Ovarian1
3CompletedTreatmentNeuroblastomas3
3CompletedTreatmentPrimary Peritoneal Carcinoma / Primary Peritoneal Cavity Cancer / Stage III Ovarian Cancer / Stage III Ovarian Epithelial Cancer / Stage IV Ovarian Cancer / Stage IV Ovarian Epithelial Cancer1
3CompletedTreatmentTumors, Solid1
3RecruitingTreatmentChildhood Ganglioneuroblastoma / Childhood Neuroblastoma / INRG Stage L2 / INRG Stage M / INRG Stage MS / NMYC Gene Amplification / Recurrent Neuroblastoma1
3RecruitingTreatmentLung Cancer Small Cell Lung Cancer (SCLC)2
3RecruitingTreatmentNeoplasms, Ovarian1
3TerminatedTreatmentExtensive Disease / First-Line / Lung Cancer Small Cell Lung Cancer (SCLC)1
3TerminatedTreatmentOvarian Epithelial Cancer1
3Unknown StatusTreatmentNeuroblastomas1
3Unknown StatusTreatmentSarcomas1
3WithdrawnTreatmentSarcomas1
4CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
Not AvailableCompletedNot AvailableCervical Intraepithelial Neoplasia (CIN)2
Not AvailableCompletedNot AvailableLung Cancer Small Cell Lung Cancer (SCLC)2
Not AvailableCompletedTreatmentDisseminated Neuroblastoma / Ganglioneuroblastoma / Localized Resectable Neuroblastoma / Localized Unresectable Neuroblastoma / Regional Neuroblastoma / Stage 4S Neuroblastoma1
Not AvailableCompletedTreatmentEwing Sarcoma of Bone / Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor1
Not AvailableRecruitingNot AvailableCancer of the Ovary1
Not AvailableRecruitingTreatmentNeuroblastomas2
Not AvailableSuspendedTreatmentDisseminated Neuroblastoma / Localized Resectable Neuroblastoma / Localized Unresectable Neuroblastoma / Regional Neuroblastoma / Stage 4S Neuroblastoma1
Not AvailableTerminatedTreatmentCancer of the Ovary1
Not AvailableWithdrawnTreatmentAdult Supratentorial Primitive Neuroectodermal Tumor (PNET) / Ewing Sarcoma of Bone / Extraosseous Ewing Sarcoma / Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor1
Not AvailableWithdrawnTreatmentMalignant Lymphomas / Tumors, Central Nervous System1
Not AvailableWithdrawnTreatmentRetinoblastoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • GlaxoSmithKline Inc.
  • Pfizer Animal Health
Dosage forms
FormRouteStrength
CapsuleOral.25 mg/1
CapsuleOral0.25 mg
CapsuleOral0.25 mg/1
CapsuleOral1 mg/1
CapsuleOral1 mg
Powder, for solutionIntravenous4 mg
Powder, for solutionIntravenous1 mg
Injection, powder, for solutionIntravenous1 mg
Injection, powder, for solutionIntravenous4 mg
InjectionIntravenous1 mg/1mL
Injection, powder, for solutionIntravenous4 mg/4mL
Injection, powder, lyophilized, for solutionIntravenous4 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous4 mg/4mL
SolutionIntravenous1 mg
Injection, solution, concentrateIntravenous1 mg/1ml
Injection, solution, concentrateIntravenous4 mg/4ml
Prices
Unit descriptionCostUnit
Hycamtin 4 mg vial1306.1USD vial
Hycamtin 1 mg capsule358.92USD capsule
Hycamtin 0.25 mg capsule89.73USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5674872No1997-10-072015-04-07Us
US5004758No1991-04-022010-05-28Us
CA2103708No2004-04-272012-02-07Canada
CA2103707No2003-12-092012-02-07Canada
US8158645No2012-04-172024-12-10Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)213-218 °CNot Available
water solubility1 mg/mlNot Available
logP0.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.861 mg/mLALOGPS
logP1.84ALOGPS
logP-0.36ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)8ChemAxon
pKa (Strongest Basic)9.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area103.2 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity115.02 m3·mol-1ChemAxon
Polarizability44.86 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8911
Blood Brain Barrier-0.9659
Caco-2 permeable-0.6966
P-glycoprotein substrateSubstrate0.7918
P-glycoprotein inhibitor INon-inhibitor0.6121
P-glycoprotein inhibitor IINon-inhibitor0.9507
Renal organic cation transporterNon-inhibitor0.9
CYP450 2C9 substrateNon-substrate0.8844
CYP450 2D6 substrateNon-substrate0.8168
CYP450 3A4 substrateSubstrate0.6875
CYP450 1A2 substrateInhibitor0.5572
CYP450 2C9 inhibitorNon-inhibitor0.8305
CYP450 2D6 inhibitorNon-inhibitor0.8918
CYP450 2C19 inhibitorNon-inhibitor0.824
CYP450 3A4 inhibitorNon-inhibitor0.6464
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7184
Ames testNon AMES toxic0.6516
CarcinogenicityNon-carcinogens0.8504
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.0075 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9963
hERG inhibition (predictor II)Non-inhibitor0.8302
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00b9-0019400000-11f24a2a9b88f6c67514

Taxonomy

Description
This compound belongs to the class of organic compounds known as camptothecins. These are heterocyclic compounds comprising a planar pentacyclic ring structure, that includes a pyrrolo[3,4-beta]-quinoline moiety (rings A, B and C), conjugated pyridone moiety (ring D) and one chiral center at position 20 within the alpha-hydroxy lactone ring with (S) configuration (the E-ring).
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Camptothecins
Sub Class
Not Available
Direct Parent
Camptothecins
Alternative Parents
Hydroxyquinolines / Pyranopyridines / Pyridinones / 1-hydroxy-2-unsubstituted benzenoids / Aralkylamines / Tertiary alcohols / Heteroaromatic compounds / Trialkylamines / Amino acids and derivatives / Lactones
show 9 more
Substituents
Camptothecin / Hydroxyquinoline / Pyranopyridine / Quinoline / 1-hydroxy-2-unsubstituted benzenoid / Pyridinone / Aralkylamine / Benzenoid / Pyridine / Heteroaromatic compound
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
pyranoindolizinoquinoline (CHEBI:63632)

Targets

Details
1. DNA topoisomerase 1
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Poly(a) rna binding
Specific Function
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a singl...
Gene Name
TOP1
Uniprot ID
P11387
Uniprot Name
DNA topoisomerase 1
Molecular Weight
90725.19 Da
References
  1. Schmidt F, Rieger J, Wischhusen J, Naumann U, Weller M: Glioma cell sensitivity to topotecan: the role of p53 and topotecan-induced DNA damage. Eur J Pharmacol. 2001 Jan 19;412(1):21-5. [PubMed:11166732]
  2. strel'tsov SA, Mikheikin AL, Nechipurenko IuD: [Interaction of topotecan--a DNA topoisomerase I inhibitor--with dual-stranded polydeoxyribonucleotides. II. Formation of a complex containing several DNA molecules in the presence of topotecan]. Mol Biol (Mosk). 2001 May-Jun;35(3):442-50. [PubMed:11443926]
  3. Streltsov SA: Action models for the antitumor drug camptothecin: formation of alkali-labile complex with DNA and inhibition of human DNA topoisomerase I. J Biomol Struct Dyn. 2002 Dec;20(3):447-54. [PubMed:12437383]
  4. Zhang J, Pu SP, Zhou YJ: [Preliminary study of apoptosis of human hepatocarcinoma cell line HepG2 induced by topotecan]. Ai Zheng. 2002 Dec;21(12):1305-9. [PubMed:12520736]
  5. Aisner J, Musanti R, Beers S, Smith S, Locsin S, Rubin EH: Sequencing topotecan and etoposide plus cisplatin to overcome topoisomerase I and II resistance: a pharmacodynamically based Phase I trial. Clin Cancer Res. 2003 Jul;9(7):2504-9. [PubMed:12855624]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Kollmannsberger C, Mross K, Jakob A, Kanz L, Bokemeyer C: Topotecan - A novel topoisomerase I inhibitor: pharmacology and clinical experience. Oncology. 1999;56(1):1-12. [PubMed:9885371]
  8. Herben VM, ten Bokkel Huinink WW, Beijnen JH: Clinical pharmacokinetics of topotecan. Clin Pharmacokinet. 1996 Aug;31(2):85-102. [PubMed:8853931]
  9. Dennis MJ, Beijnen JH, Grochow LB, van Warmerdam LJ: An overview of the clinical pharmacology of topotecan. Semin Oncol. 1997 Feb;24(1 Suppl 5):S5-12-S5-18. [PubMed:9122737]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function
Releases the supercoiling and torsional tension of DNA introduced during duplication of mitochondrial DNA by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-str...
Gene Name
TOP1MT
Uniprot ID
Q969P6
Uniprot Name
DNA topoisomerase I, mitochondrial
Molecular Weight
69871.39 Da
References
  1. Kosovsky MJ, Soslau G: Immunological identification of human platelet mitochondrial DNA topoisomerase I. Biochim Biophys Acta. 1993 Jun 24;1164(1):101-7. [PubMed:8390858]
3. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Intercalation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB Jr, Stewart L: The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15387-92. Epub 2002 Nov 8. [PubMed:12426403]
  2. Pourquier P, Takebayashi Y, Urasaki Y, Gioffre C, Kohlhagen G, Pommier Y: Induction of topoisomerase I cleavage complexes by 1-beta -D-arabinofuranosylcytosine (ara-C) in vitro and in ara-C-treated cells. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1885-90. [PubMed:10677551]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Dubey S, Hutson P, Alberti D, Arzoomanian R, Binger K, Volkman J, Feierabend C, Wilding G, Schiller JH: Phase I study of docetaxel and topotecan in patients with advanced malignancies. J Oncol Pharm Pract. 2005 Dec;11(4):131-8. doi: 10.1191/1078155205jp161oa. [PubMed:16595064]
  3. Schuetz E, Lan L, Yasuda K, Kim R, Kocarek TA, Schuetz J, Strom S: Development of a real-time in vivo transcription assay: application reveals pregnane X receptor-mediated induction of CYP3A4 by cancer chemotherapeutic agents. Mol Pharmacol. 2002 Sep;62(3):439-45. [PubMed:12181418]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Houghton PJ, Germain GS, Harwood FC, Schuetz JD, Stewart CF, Buchdunger E, Traxler P: Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res. 2004 Apr 1;64(7):2333-7. [PubMed:15059881]
  2. Maliepaard M, van Gastelen MA, Tohgo A, Hausheer FH, van Waardenburg RC, de Jong LA, Pluim D, Beijnen JH, Schellens JH: Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res. 2001 Apr;7(4):935-41. [PubMed:11309344]
  3. Sugimoto Y, Tsukahara S, Imai Y, Sugimoto Y, Ueda K, Tsuruo T: Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists. Mol Cancer Ther. 2003 Jan;2(1):105-12. [PubMed:12533678]
  4. Maliepaard M, van Gastelen MA, de Jong LA, Pluim D, van Waardenburg RC, Ruevekamp-Helmers MC, Floot BG, Schellens JH: Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res. 1999 Sep 15;59(18):4559-63. [PubMed:10493507]
  5. Jonker JW, Smit JW, Brinkhuis RF, Maliepaard M, Beijnen JH, Schellens JH, Schinkel AH: Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst. 2000 Oct 18;92(20):1651-6. [PubMed:11036110]
  6. Allen JD, Van Dort SC, Buitelaar M, van Tellingen O, Schinkel AH: Mouse breast cancer resistance protein (Bcrp1/Abcg2) mediates etoposide resistance and transport, but etoposide oral availability is limited primarily by P-glycoprotein. Cancer Res. 2003 Mar 15;63(6):1339-44. [PubMed:12649196]
  7. Breedveld P, Zelcer N, Pluim D, Sonmezer O, Tibben MM, Beijnen JH, Schinkel AH, van Tellingen O, Borst P, Schellens JH: Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions. Cancer Res. 2004 Aug 15;64(16):5804-11. [PubMed:15313923]
  8. Carcaboso AM, Elmeliegy MA, Shen J, Juel SJ, Zhang ZM, Calabrese C, Tracey L, Waters CM, Stewart CF: Tyrosine kinase inhibitor gefitinib enhances topotecan penetration of gliomas. Cancer Res. 2010 Jun 1;70(11):4499-508. doi: 10.1158/0008-5472.CAN-09-4264. Epub 2010 May 11. [PubMed:20460504]
  9. Shen J, Carcaboso AM, Hubbard KE, Tagen M, Wynn HG, Panetta JC, Waters CM, Elmeliegy MA, Stewart CF: Compartment-specific roles of ATP-binding cassette transporters define differential topotecan distribution in brain parenchyma and cerebrospinal fluid. Cancer Res. 2009 Jul 15;69(14):5885-92. doi: 10.1158/0008-5472.CAN-09-0700. Epub 2009 Jun 30. [PubMed:19567673]
  10. Rocchi E, Khodjakov A, Volk EL, Yang CH, Litman T, Bates SE, Schneider E: The product of the ABC half-transporter gene ABCG2 (BCRP/MXR/ABCP) is expressed in the plasma membrane. Biochem Biophys Res Commun. 2000 Apr 29;271(1):42-6. [PubMed:10777678]
  11. Ishii M, Iwahana M, Mitsui I, Minami M, Imagawa S, Tohgo A, Ejima A: Growth inhibitory effect of a new camptothecin analog, DX-8951f, on various drug-resistant sublines including BCRP-mediated camptothecin derivative-resistant variants derived from the human lung cancer cell line PC-6. Anticancer Drugs. 2000 Jun;11(5):353-62. [PubMed:10912951]
  12. Yang CH, Schneider E, Kuo ML, Volk EL, Rocchi E, Chen YC: BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells. Biochem Pharmacol. 2000 Sep 15;60(6):831-7. [PubMed:10930538]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Collett A, Tanianis-Hughes J, Hallifax D, Warhurst G: Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo. Pharm Res. 2004 May;21(5):819-26. [PubMed:15180340]
  2. Carcaboso AM, Elmeliegy MA, Shen J, Juel SJ, Zhang ZM, Calabrese C, Tracey L, Waters CM, Stewart CF: Tyrosine kinase inhibitor gefitinib enhances topotecan penetration of gliomas. Cancer Res. 2010 Jun 1;70(11):4499-508. doi: 10.1158/0008-5472.CAN-09-4264. Epub 2010 May 11. [PubMed:20460504]
  3. Shen J, Carcaboso AM, Hubbard KE, Tagen M, Wynn HG, Panetta JC, Waters CM, Elmeliegy MA, Stewart CF: Compartment-specific roles of ATP-binding cassette transporters define differential topotecan distribution in brain parenchyma and cerebrospinal fluid. Cancer Res. 2009 Jul 15;69(14):5885-92. doi: 10.1158/0008-5472.CAN-09-0700. Epub 2009 Jun 30. [PubMed:19567673]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [PubMed:17509534]
  2. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [PubMed:23241029]
  3. Xu Y, Liu X, Wang Y, Zhou N, Peng J, Gong L, Ren J, Luo C, Luo X, Jiang H, Chen K, Zheng M: Combinatorial Pharmacophore Modeling of Multidrug and Toxin Extrusion Transporter 1 Inhibitors: a Theoretical Perspective for Understanding Multiple Inhibitory Mechanisms. Sci Rep. 2015 Sep 2;5:13684. doi: 10.1038/srep13684. [PubMed:26330298]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Data based on in vitro studies.
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [PubMed:17509534]
  2. Raj GM, Mathaiyan J, Wyawahare M, Rao KS, Priyadarshini R: Genetic polymorphisms of multidrug and toxin extrusion proteins (MATE1 and MATE2) in South Indian population. Bioimpacts. 2017;7(1):25-30. doi: 10.15171/bi.2017.04. Epub 2017 Feb 8. [PubMed:28546950]
  3. Drug-transporter interaction testing in drug discovery and development [Link]

Drug created on June 13, 2005 07:24 / Updated on December 14, 2018 12:39