Cediranib

Identification

Name
Cediranib
Accession Number
DB04849  (DB12033)
Type
Small Molecule
Groups
Investigational
Description

The novel indole-ether quinazoline Cediranib is a highly potent (IC50 < 1 nmol/L) ATP-competitive inhibitor of recombinant KDR tyrosine kinase in vitro. It is being developed clinically as a once-daily oral therapy for the treatment of cancer.

Structure
Thumb
Synonyms
Not Available
External IDs
AZD-2171 / AZD2171
Product Ingredients
IngredientUNIICASInChI Key
Cediranib maleate68AYS9A614857036-77-2JRMGHBVACUJCRP-BTJKTKAUSA-N
International/Other Brands
Recentin
Categories
UNII
NQU9IPY4K9
CAS number
288383-20-0
Weight
Average: 450.5053
Monoisotopic: 450.206718955
Chemical Formula
C25H27FN4O3
InChI Key
XXJWYDDUDKYVKI-UHFFFAOYSA-N
InChI
InChI=1S/C25H27FN4O3/c1-16-12-17-19(29-16)6-7-21(24(17)26)33-25-18-13-22(31-2)23(14-20(18)27-15-28-25)32-11-5-10-30-8-3-4-9-30/h6-7,12-15,29H,3-5,8-11H2,1-2H3
IUPAC Name
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline
SMILES
COC1=CC2=C(C=C1OCCCN1CCCC1)N=CN=C2OC1=C(F)C2=C(NC(C)=C2)C=C1

Pharmacology

Indication

For the treatment of liver cancer, advanced non-small cell lung cancer (NSCLC), advanced colorectal cancer (CRC) and other solid tumors.

Structured Indications
Not Available
Pharmacodynamics

Cediranib is a once-daily, orally available, highly potent and selective VEGF signalling inhibitor that inhibits all three VEGF receptors. The preclinical profile of Cediranib indicates that it has the potential to be the 'best in class' VEGF signalling inhibitor. Phase I data indicate that Cediranib is generally well tolerated, with the most common dose related adverse events being diarrhoea, hoarseness, headache and hypertension.

Mechanism of action

Cediranib inhibits vacular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK). By forming a blockade at the VEGF receptors, Cediranib limits the growth of new blood vessels, which are essential to supporting tumor growth. Thus, lacking sufficient blood supply, tumor cells become starved for nutrients, slowing or halting growth and potentially improving the efficacy of other treatments. Preclinical evidence indicated that the drug had a high affinity at these sites, and was well tolerated and efficacious in animal studies.

TargetActionsOrganism
UVascular endothelial growth factor receptor 2Not AvailableHuman
Absorption

Available following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

12 to 35 hours

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

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Cediranib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Cediranib.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Cediranib.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Cediranib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Cediranib.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Cediranib.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Cediranib.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Cediranib.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Cediranib.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Cediranib.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Cediranib.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Cediranib.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Cediranib.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Cediranib.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Cediranib.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Cediranib.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Cediranib.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Cediranib.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Cediranib.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Cediranib.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO, Chester R, Jackson JA, Boffey SJ, Kilburn LL, Barnett S, Richmond GH, Wadsworth PF, Walker M, Bigley AL, Taylor ST, Cooper L, Beck S, Jurgensmeier JM, Ogilvie DJ: AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005 May 15;65(10):4389-400. [PubMed:15899831]
External Links
PubChem Compound
9933475
PubChem Substance
175426860
ChemSpider
8109103
BindingDB
50331096
ChEBI
94782
ChEMBL
CHEMBL491473
Wikipedia
AZD2171
ATC Codes
L01XE32 — Cediranib

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentCancer, Ovarian1
1Active Not RecruitingTreatmentCancer, Ovarian / Cervical Cancers / Endometrial Cancers / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm1
1Active Not RecruitingTreatmentSolid Neoplasms / Stage IV Cutaneous Melanoma AJCC v6 and v7 / Stage IV Skin Melanoma1
1Active Not RecruitingTreatmentTumors, Solid1
1CompletedNot AvailableCancers1
1CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Refractory or Recurrent Solid Tumors1
1CompletedTreatmentAcute / Leukemias / Myelocytic1
1CompletedTreatmentAdult Anaplastic Astrocytoma / Adult Anaplastic Ependymoma / Adult Anaplastic Oligodendroglioma / Adult Brain Stem Glioma / Adult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma / Adult Mixed Glioma / Adult Solid Neoplasm / Male Breast Carcinoma / Recurrent Adult Brain Neoplasm / Recurrent Breast Carcinoma / Recurrent Colon Carcinoma / Recurrent Melanoma / Recurrent Non-Small Cell Lung Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Ovarian Germ Cell Tumor / Recurrent Pancreatic Carcinoma / Recurrent Rectal Carcinoma / Renal Cell Carcinoma Recurrent / Stage III Pancreatic Cancer / Stage III Renal Cell Cancer / Stage IIIA Colon Cancer / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIA Ovarian Cancer / Stage IIIA Ovarian Germ Cell Tumor / Stage IIIA Rectal Cancer / Stage IIIA Skin Melanoma / Stage IIIB Breast Cancer / Stage IIIB Colon Cancer / Stage IIIb Non-small Cell Lung Cancer / Stage IIIB Ovarian Cancer / Stage IIIB Ovarian Germ Cell Tumor / Stage IIIB Rectal Cancer / Stage IIIB Skin Melanoma / Stage IIIC Breast Cancer / Stage IIIC Colon Cancer / Stage IIIC Ovarian Cancer / Stage IIIC Ovarian Germ Cell Tumor / Stage IIIC Rectal Cancer / Stage IIIC Skin Melanoma / Stage IV Breast Cancer / Stage IV Non-Small Cell Lung Cancer / Stage IV Ovarian Cancer / Stage IV Ovarian Germ Cell Tumor / Stage IV Pancreatic Cancer / Stage IV Renal Cell Cancer / Stage IV Skin Melanoma / Stage IVA Colon Cancer / Stage IVA Rectal Cancer / Stage IVB Colon Cancer / Stage IVB Rectal Cancer1
1CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma / Recurrent Adult Brain Neoplasm1
1CompletedTreatmentAdult Grade III Lymphomatoid Granulomatosis / Adult Nasal Type Extranodal NK/T-Cell Lymphoma / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Childhood Burkitt Lymphoma / Childhood Diffuse Large Cell Lymphoma / Childhood Grade III Lymphomatoid Granulomatosis / Childhood Immunoblastic Large Cell Lymphoma / Childhood Nasal Type Extranodal NK/T-cell Lymphoma / Cutaneous B-Cell Non-Hodgkin Lymphoma / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Hepatosplenic T-Cell Lymphoma / Intraocular Lymphoma / Nodal marginal zone B-cell lymphomas / Noncutaneous Extranodal Lymphoma / Peripheral T-Cell Lymphoma (PTCL) / Progressive Hairy Cell Leukemia, Initial Treatment / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Childhood Anaplastic Large Cell Lymphoma / Recurrent Childhood Large Cell Lymphoma / Recurrent Childhood Lymphoblastic Lymphoma / Recurrent Childhood Small Noncleaved Cell Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Recurrent/Refractory Childhood Hodgkin Lymphoma / Refractory Hairy Cell Leukemia / Small Intestine Lymphoma / Splenic Marginal Zone Lymphoma / Stage IV Adult Burkitt Lymphoma / Stage IV Adult Diffuse Large Cell Lymphoma / Stage IV Adult Diffuse Mixed Cell Lymphoma / Stage IV Adult Diffuse Small Cleaved Cell Lymphoma / Stage IV Adult Hodgkin Lymphoma / Stage IV Adult Immunoblastic Large Cell Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Adult T-Cell Leukemia/Lymphoma / Stage IV Childhood Anaplastic Large Cell Lymphoma / Stage IV Childhood Hodgkin Lymphoma / Stage IV Childhood Large Cell Lymphoma / Stage IV Childhood Lymphoblastic Lymphoma / Stage IV Childhood Small Noncleaved Cell Lymphoma / Stage IV Grade 1 Follicular Lymphoma / Stage IV Grade 2 Follicular Lymphoma / Stage IV Grade 3 Follicular Lymphoma / Stage IV Mantle Cell Lymphoma / Stage IVA Mycosis Fungoides/Sezary Syndrome / Stage IVB Mycosis Fungoides/Sezary Syndrome / T-Cell Large Granular Lymphocyte Leukemia / Testicular Lymphoma / Unspecified Adult Solid Tumor, Protocol Specific / Unspecified Childhood Solid Tumor, Protocol Specific / Waldenstrom's Macroglobulinemia (WM)1
1CompletedTreatmentAdvanced Prostate Adenocarcinoma1
1CompletedTreatmentAdvanced Solid Malignancies1
1CompletedTreatmentAdvanced Solid Metastatic Tumor1
1CompletedTreatmentAdvanced Solid Tumors3
1CompletedTreatmentAdvanced Solid Tumors / Hepatic Metastases1
1CompletedTreatmentAdvanced Tumor1
1CompletedTreatmentCancer, Advanced / Hepatic Impairment1
1CompletedTreatmentCarcinoma NOS / Lung Cancer Non-Small Cell Cancer (NSCLC) / Neoplasms, Head and Neck1
1CompletedTreatmentChildhood Atypical Teratoid/Rhabdoid Tumor / Childhood Central Nervous System Germ Cell Tumor / Childhood Cerebral Anaplastic Astrocytoma / Childhood Cerebral Astrocytoma / Childhood Grade I Meningioma / Childhood Grade II Meningioma / Childhood Grade III Meningioma / Childhood Infratentorial Ependymoma / Childhood Oligodendroglioma / Childhood Spinal Cord Neoplasm / Childhood Supratentorial Ependymoma / Recurrent Childhood Brain Neoplasm / Recurrent Childhood Brain Stem Glioma / Recurrent Childhood Cerebellar Astrocytoma / Recurrent Childhood Cerebral Astrocytoma / Recurrent Childhood Ependymoma / Recurrent Childhood Medulloblastoma / Recurrent Childhood Pineoblastoma / Recurrent Childhood Subependymal Giant Cell Astrocytoma / Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor / Recurrent Childhood Visual Pathway Glioma1
1CompletedTreatmentColorectal Cancers / Lung Cancers1
1CompletedTreatmentColorectal Cancers / Lung Cancers / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentLung Cancers1
1CompletedTreatmentMalignant Neoplasm of Stomach1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentNeoplasms, Brain / Recurrent Glioblastoma1
1TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1TerminatedTreatmentMale Breast Cancer / Stage IV Breast Cancer / Stage IV Melanoma / Stage IV Non-Small Cell Lung Cancer / Stage IV Renal Cell Cancer / Stage IVA Colon Cancer / Stage IVA Rectal Cancer / Stage IVB Colon Cancer / Stage IVB Rectal Cancer / Tumors Metastatic to Brain1
1TerminatedTreatmentRectal Carcinoma1
1, 2Active Not RecruitingTreatmentAdvanced Malignant Mesothelioma / Epithelioid Mesothelioma / Pleural Malignant Mesothelioma / Recurrent Malignant Mesothelioma / Sarcomatoid Mesothelioma1
1, 2Active Not RecruitingTreatmentDeleterious BRCA1 Gene Mutation / Deleterious BRCA2 Gene Mutation / Estrogen Receptor Negative / HER2/Neu Negative / Ovarian Endometrioid Adenocarcinoma / Ovarian Serous Adenocarcinoma / Ovarian Serous Cystadenocarcinoma / Ovarian Serous Surface Papillary Adenocarcinoma / Progesterone Receptor Negative / Recurrent Breast Carcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma / Triple-Negative Breast Carcinoma1
1, 2Active Not RecruitingTreatmentRecurrent Thyroid Gland Carcinoma / Stage I Thyroid Gland Follicular Carcinoma / Stage I Thyroid Gland Papillary Carcinoma / Stage II Thyroid Gland Follicular Carcinoma / Stage II Thyroid Gland Papillary Carcinoma / Stage III Thyroid Gland Follicular Carcinoma / Stage III Thyroid Gland Papillary Carcinoma / Stage IV Thyroid Gland Follicular Carcinoma / Stage IV Thyroid Gland Papillary Carcinoma / Stage IVA Thyroid Gland Follicular Carcinoma / Stage IVA Thyroid Gland Papillary Carcinoma / Stage IVB Thyroid Gland Follicular Carcinoma / Stage IVB Thyroid Gland Papillary Carcinoma / Stage IVC Thyroid Gland Follicular Carcinoma / Stage IVC Thyroid Gland Papillary Carcinoma1
1, 2CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma1
1, 2CompletedTreatmentMetastatic Colorectal Cancers1
1, 2RecruitingTreatmentCancer, Breast / Cancer, Ovarian / Colorectal Cancers / Lung Cancers / Prostate Cancer / Triple Negative Breast Cancer (TNBC)1
2Active Not RecruitingTreatmentAlveolar Soft Part Sarcoma (ASPS)1
2Active Not RecruitingTreatmentAlveolar Soft-part Sarcoma1
2Active Not RecruitingTreatmentBRCA1 Gene Mutation / Brca2 Gene Mutation / Deleterious BRCA1 Gene Mutation / Deleterious BRCA2 Gene Mutation / Fallopian Tube Endometrioid Adenocarcinoma / Fallopian Tube Serous Adenocarcinoma / High Grade Ovarian Serous Adenocarcinoma / Ovarian Endometrioid Tumor / Primary Peritoneal Serous Adenocarcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2Active Not RecruitingTreatmentCancer, Ovarian1
2Active Not RecruitingTreatmentNeurofibromatosis Type 1 / Plexiform Neurofibroma / Spinal Cord Neurofibroma1
2CompletedTreatmentAcral Lentiginous Malignant Melanoma / Ciliary Body and Choroid Melanoma, Medium/Large Size / Ciliary Body and Choroid Melanoma, Small Size / Extraocular Extension Melanoma / Intraocular Melanoma / Iris Melanoma / Lentigo Maligna Malignant Melanoma / Recurrent Melanoma / Stage IV Melanoma / Stage, Intraocular Melanoma / Superficial Spreading Malignant Melanoma1
2CompletedTreatmentAdult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / De Novo Myelodysplastic Syndromes / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia / Secondary Myelodysplastic Syndromes / Untreated Adult Acute Myeloid Leukemia1
2CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma / Recurrent Adult Brain Tumor1
2CompletedTreatmentAdult Glioblastoma / Adult Gliosarcoma1
2CompletedTreatmentAdult Primary Cholangiocellular Carcinoma / Advanced Adult Primary Liver Cancer / Cholangiocarcinoma of the Extrahepatic Bile Duct / Cholangiocarcinoma of the Gallbladder / Localized Unresectable Adult Primary Liver Cancer / Periampullary Adenocarcinoma / Recurrent Adult Primary Liver Cancer / Recurrent Extrahepatic Bile Duct Cancer / Recurrent Gallbladder Cancer / Unresectable Extrahepatic Bile Duct Cancer / Unresectable Gallbladder Cancer1
2CompletedTreatmentAdult Primary Hepatocellular Carcinoma / Advanced Adult Primary Liver Cancer / Localized Unresectable Adult Primary Liver Cancer1
2CompletedTreatmentAdvanced Breast Cancer1
2CompletedTreatmentAdvanced Malignant Mesothelioma / Epithelial Mesothelioma / Localized Malignant Mesothelioma / Recurrent Malignant Mesothelioma / Sarcomatous Mesothelioma1
2CompletedTreatmentAdvanced Malignant Mesothelioma / Epithelial Mesothelioma / Recurrent Malignant Mesothelioma / Sarcomatous Mesothelioma1
2CompletedTreatmentB-Cell Chronic Lymphocytic Leukemia / Refractory Chronic Lymphocytic Leukemia1
2CompletedTreatmentCancers1
2CompletedTreatmentCervical Cancers1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentEndometrial Adenocarcinomas / Endometrial Adenosquamous Carcinoma / Endometrial Clear Cell Adenocarcinoma / Endometrial Serous Adenocarcinoma / Recurrent Uterine Corpus Carcinoma1
2CompletedTreatmentFallopian Tube Cancer / Primary Peritoneal Serous Adenocarcinoma / Recurrent Ovarian Epithelial Cancer / Stage I Ovarian Epithelial Cancer / Stage II Ovarian Epithelial Cancer1
2CompletedTreatmentGastrointestinal Stromal Tumors / Soft Tissue Sarcoma (STS)1
2CompletedTreatmentLung Cancers1
2CompletedTreatmentMale Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentRecurrent Hypopharyngeal Squamous Cell Carcinoma / Recurrent Laryngeal Squamous Cell Carcinoma / Recurrent Laryngeal Verrucous Carcinoma / Recurrent Lip and Oral Cavity Squamous Cell Carcinoma / Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary / Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma / Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma / Recurrent Oral Cavity Verrucous Carcinoma / Recurrent Oropharyngeal Squamous Cell Carcinoma / Recurrent Salivary Gland Carcinoma / Salivary Gland Squamous Cell Carcinoma / Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary / Stage IV Hypopharyngeal Squamous Cell Carcinoma / Stage IV Laryngeal Squamous Cell Carcinoma / Stage IV Laryngeal Verrucous Carcinoma / Stage IV Lip and Oral Cavity Squamous Cell Carcinoma / Stage IV Major Salivary Gland Carcinoma / Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma / Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma / Stage IV Oral Cavity Verrucous Carcinoma / Stage IV Oropharyngeal Squamous Cell Carcinoma / Tongue Carcinoma / Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary1
2CompletedTreatmentRecurrent Non-small Cell Lung Cancer2
2CompletedTreatmentRenal Cell Adenocarcinoma1
2CompletedTreatmentRenal Cell Carcinoma Recurrent / Stage IV Renal Cell Cancer1
2CompletedTreatmentTumors1
2RecruitingTreatmentAdenocarcinoma of the Pancreas / BRCA1 wt Allele / BRCA2 wt Allele / Estrogen Receptor Negative / HER2/Neu Negative / Pancreatic Adenocarcinoma Metastatic / Pancreatic Ductal Adenocarcinoma / Progesterone Receptor Negative / Recurrent Breast Carcinoma / Recurrent Non-Small Cell Lung Carcinoma / Recurrent Pancreatic Carcinoma / Recurrent Small Cell Lung Carcinoma / Stage III Breast Cancer / Stage III Breast Cancer AJCC V7 / Stage III Non-Small Cell Lung Cancer / Stage III Non-Small Cell Lung Cancer AJCC v7 / Stage III Pancreatic Cancer / Stage III Pancreatic Cancer AJCC v6 and v7 / Stage III Small Cell Lung Carcinoma / Stage III Small Cell Lung Carcinoma AJCC v7 / Stage IIIA Breast Cancer / Stage IIIA Breast Cancer AJCC v7 / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIA Non-Small Cell Lung Cancer AJCC v7 / Stage IIIA Small Cell Lung Carcinoma / Stage IIIA Small Cell Lung Carcinoma AJCC v7 / Stage IIIB Breast Cancer / Stage IIIB Breast Cancer AJCC v7 / Stage IIIb Non-small Cell Lung Cancer / Stage IIIB Non-Small Cell Lung Cancer AJCC v7 / Stage IIIB Small Cell Lung Carcinoma / Stage IIIB Small Cell Lung Carcinoma AJCC v7 / Stage IIIC Breast Cancer / Stage IIIC Breast Cancer AJCC v7 / Stage IV Breast Cancer / Stage IV Breast Cancer AJCC v6 and v7 / Stage IV Non-Small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer AJCC v7 / Stage IV Pancreatic Cancer / Stage IV Pancreatic Cancer AJCC v6 and v7 / Stage IV Small Cell Lung Carcinoma / Stage IV Small Cell Lung Carcinoma AJCC v7 / Stage IVA Pancreatic Cancer / Stage IVB Pancreatic Cancer / Triple-Negative Breast Carcinoma / Unresectable Pancreatic Carcinoma1
2RecruitingTreatmentAlveolar Soft Part Sarcoma (ASPS)1
2RecruitingTreatmentCancer, Ovarian1
2RecruitingTreatmentCastration Levels of Testosterone / Castration-Resistant Prostate Carcinoma / Hormone-Resistant Prostate Cancer / Metastatic Hormone Refractory Prostate Cancer / Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation / Prostate Carcinoma Metastatic in the Bone / Prostate Small Cell Carcinoma / PSA Progression / Stage IV Prostate Adenocarcinoma1
2RecruitingTreatmentNeoplasms, Ovarian1
2RecruitingTreatmentRecurrent Glioblastoma1
2RecruitingTreatmentRecurrent Platinum Resistant Ovarian Cancer1
2SuspendedTreatmentSmall Cell Lung Carcinoma1
2TerminatedTreatmentAdenocarcinoma of the Prostate / Stage IV Prostate Cancer1
2TerminatedTreatmentAdult Primary Hepatocellular Carcinoma / Advanced Adult Primary Liver Cancer / Localized Unresectable Adult Primary Liver Cancer / Recurrent Adult Primary Liver Cancer1
2TerminatedTreatmentClear Cell Renal Cell Carcinoma / Recurrent Renal Cell Cancer / Stage IV Renal Cell Cancer1
2TerminatedTreatmentColorectal Cancers1
2TerminatedTreatmentGlioblastomas1
2TerminatedTreatmentMalignant Ascites / Malignant Pleural Effusions1
2Unknown StatusTreatmentHormone-Resistant Prostate Cancer / Recurrent Prostate Cancer1
2Unknown StatusTreatmentRecurrent Fallopian Tube Cancer / Recurrent Ovarian Epithelial Cancer / Recurrent Primary Peritoneal Cavity Cancer1
2, 3CompletedTreatmentBiliary Tract Neoplasms1
2, 3CompletedTreatmentColorectal Cancers1
2, 3CompletedTreatmentLung Cancers1
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 / 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 / Primary Peritoneal Serous Adenocarcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma / Undifferentiated Fallopian Tube Carcinoma / Undifferentiated Ovarian Carcinoma1
3CompletedTreatmentLung Cancers1
3CompletedTreatmentMetastatic Colorectal Cancers1
3CompletedTreatmentRecurrent Glioblastoma1
3Not Yet RecruitingTreatmentCancer, Ovarian1
3RecruitingTreatmentBRCA Rearrangement / Deleterious BRCA1 Gene Mutation / Deleterious BRCA2 Gene Mutation / Endometrial Undifferentiated Carcinoma / Fallopian Tube Clear Cell Adenocarcinoma / Fallopian Tube Transitional Cell Carcinoma / Malignant Ovarian Mixed Epithelial Tumor / Ovarian Clear Cell Adenocarcinoma / Ovarian Endometrioid Tumor / Ovarian Seromucinous Carcinoma / Ovarian Serous Tumor / Ovarian Transitional Cell Carcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma / Undifferentiated Fallopian Tube Carcinoma / Undifferentiated Ovarian Carcinoma1
3Unknown StatusTreatmentCancer, Ovarian1
Not AvailableCompletedTreatmentCancer, Breast1
Not AvailableRecruitingTreatmentCancer, Ovarian1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0155 mg/mLALOGPS
logP3.77ALOGPS
logP4.13ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)16.59ChemAxon
pKa (Strongest Basic)9.14ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area72.5 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity125.16 m3·mol-1ChemAxon
Polarizability48.77 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9928
Blood Brain Barrier+0.972
Caco-2 permeable+0.5919
P-glycoprotein substrateSubstrate0.6286
P-glycoprotein inhibitor IInhibitor0.7308
P-glycoprotein inhibitor IIInhibitor0.8118
Renal organic cation transporterInhibitor0.6936
CYP450 2C9 substrateNon-substrate0.8505
CYP450 2D6 substrateNon-substrate0.5395
CYP450 3A4 substrateSubstrate0.7607
CYP450 1A2 substrateInhibitor0.6053
CYP450 2C9 inhibitorNon-inhibitor0.5716
CYP450 2D6 inhibitorNon-inhibitor0.6498
CYP450 2C19 inhibitorInhibitor0.7982
CYP450 3A4 inhibitorInhibitor0.6267
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.922
Ames testNon AMES toxic0.641
CarcinogenicityNon-carcinogens0.9197
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5985 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7652
hERG inhibition (predictor II)Inhibitor0.8887
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 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

Taxonomy

Description
This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Ethers
Direct Parent
Diarylethers
Alternative Parents
Quinazolines / Indoles / Anisoles / Alkyl aryl ethers / Substituted pyrroles / Pyrimidines and pyrimidine derivatives / N-alkylpyrrolidines / Aryl fluorides / Heteroaromatic compounds / Trialkylamines
show 4 more
Substituents
Diaryl ether / Diazanaphthalene / Quinazoline / Indole / Indole or derivatives / Anisole / Alkyl aryl ether / Aryl fluoride / Aryl halide / Benzenoid
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO, Chester R, Jackson JA, Boffey SJ, Kilburn LL, Barnett S, Richmond GH, Wadsworth PF, Walker M, Bigley AL, Taylor ST, Cooper L, Beck S, Jurgensmeier JM, Ogilvie DJ: AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005 May 15;65(10):4389-400. [PubMed:15899831]

Drug created on October 18, 2007 14:00 / Updated on November 09, 2017 03:48