Tipifarnib

Identification

Name
Tipifarnib
Accession Number
DB04960
Type
Small Molecule
Groups
Investigational
Description

Tipifarnib (R-115777) is a substance that is being studied in the treatment of acute myeloid leukemia (AML) and other types of cancer. It belongs to the family of drugs called farnesyltransferase inhibitors. It is also called Zarnestra. In June 2005, the FDA issued a Not Approvable Letter for Zarnestra.

Structure
Thumb
Synonyms
  • Zarnestra
External IDs
R-115777 / R115777
International/Other Brands
Zarnestra
Categories
UNII
MAT637500A
CAS number
192185-72-1
Weight
Average: 489.396
Monoisotopic: 488.11706676
Chemical Formula
C27H22Cl2N4O
InChI Key
PLHJCIYEEKOWNM-HHHXNRCGSA-N
InChI
InChI=1S/C27H22Cl2N4O/c1-32-16-31-15-25(32)27(30,18-6-9-20(28)10-7-18)19-8-11-24-23(13-19)22(14-26(34)33(24)2)17-4-3-5-21(29)12-17/h3-16H,30H2,1-2H3/t27-/m1/s1
IUPAC Name
6-[(R)-amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-1,2-dihydroquinolin-2-one
SMILES
CN1C=NC=C1[[email protected]@](N)(C1=CC=C(Cl)C=C1)C1=CC2=C(C=C1)N(C)C(=O)C=C2C1=CC(Cl)=CC=C1

Pharmacology

Indication

Investigated for use/treatment in colorectal cancer, leukemia (myeloid), pancreatic cancer, and solid tumors.

Structured Indications
Not Available
Pharmacodynamics

R115777, a nonpeptidomimetic farnesyl transferase inhibitor, suppresses the growth of human pancreatic adenocarcinoma cell lines. This growth inhibition is associated with modulation in the phosphorylation levels of signal transducers and activators of transcription 3 (STAT3) and extracellular signal-regulated kinases (ERK).

Mechanism of action

The farnesyltransferase inhibitors (FTIs) are a class of experimental cancer drugs that target protein farnesyltransferase with the downstream effect of preventing the proper functioning of the Ras protein, which is commonly abnormally active in cancer. After translation, RAS goes through four steps of modification: isoprenylation, proteolysis, methylation and palmitoylation. Isoprenylation involves the enzyme farnesyltransferase (FTase) transferring a farnesyl group from farnesyl pyrophosphate (FPP) to the pre-RAS protein. Also, a related enzyme geranylgeranyltransferase I (GGTase I) has the ability to transfer a geranylgeranyl group to K and N-RAS. Farnesyl is necessary to attach RAS to the cell membrane. Without attachment to the cell membrane, RAS is not able to transfer signals from membrane receptors (Reuter et al., 2000).

TargetActionsOrganism
UProtein farnesyltransferase subunit betaNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
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 Tipifarnib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Tipifarnib.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Tipifarnib.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Tipifarnib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Tipifarnib.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Tipifarnib.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Tipifarnib.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Tipifarnib.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Tipifarnib.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Tipifarnib.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Tipifarnib.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Tipifarnib.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Tipifarnib.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Tipifarnib.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Tipifarnib.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Tipifarnib.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Tipifarnib.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Tipifarnib.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Tipifarnib.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Martin LA, Head JE, Pancholi S, Salter J, Quinn E, Detre S, Kaye S, Howes A, Dowsett M, Johnston SR: The farnesyltransferase inhibitor R115777 (tipifarnib) in combination with tamoxifen acts synergistically to inhibit MCF-7 breast cancer cell proliferation and cell cycle progression in vitro and in vivo. Mol Cancer Ther. 2007 Sep;6(9):2458-67. [PubMed:17876043]
  2. Wang CC, Liao YP, Mischel PS, Iwamoto KS, Cacalano NA, McBride WH: HDJ-2 as a target for radiosensitization of glioblastoma multiforme cells by the farnesyltransferase inhibitor R115777 and the role of the p53/p21 pathway. Cancer Res. 2006 Jul 1;66(13):6756-62. [PubMed:16818651]
External Links
PubChem Compound
159324
PubChem Substance
175426920
ChemSpider
140122
BindingDB
50370385
ChEMBL
CHEMBL289228
HET
JAN
PDB Entries
1sa4 / 1x81 / 3sfx / 4lng

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentSolid Neoplasms1
1CompletedTreatmentAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome / Adult Acute Erythroid Leukemia (M6) / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5) / 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 Del(5q) / 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 Leukemia / Untreated Adult Acute Myeloid Leukemia1
1CompletedTreatmentAdult Acute Basophilic Leukemia / Adult Acute Eosinophilic Leukemia / Adult 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(9;11)(p22;q23); MLLT3-MLL / Adult Acute Myeloid Leukemia Without Maturation / Adult Acute Myelomonocytic Leukemia / Adult Erythroleukemia / Adult Pure Erythroid Leukemia / Blastic Phase / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Recurrent Disease / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Adult Acute Myeloid Leukemia1
1CompletedTreatmentAdult 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) / Secondary Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
1CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma2
1CompletedTreatmentAdvanced Malignant Neoplasm1
1CompletedTreatmentCancers1
1CompletedTreatmentChronic Myelomonocytic Leukemia / De Novo Myelodysplastic Syndromes / Previously Treated Myelodysplastic Syndromes / Refractory Anemia / Refractory Anemia With Excess Blasts / Refractory Anemia With Excess Blasts in Transformation / Refractory Anemia With Ringed Sideroblasts / Refractory Cytopenia With Multilineage Dysplasia1
1CompletedTreatmentChronic Myeloproliferative Disorders / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes1
1CompletedTreatmentLeukemia,Myeloid, Chronic1
1CompletedTreatmentLeukemias3
1CompletedTreatmentLung Cancers1
1CompletedTreatmentMultiple Myeloma (MM)1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific3
1TerminatedTreatmentLeukemias1
1Unknown StatusTreatmentCancers1
1Unknown StatusTreatmentMalignant Neoplasm of Pancreas1
1, 2CompletedTreatmentAccelerated Phase of Disease / Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative / Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Chronic Myelomonocytic Leukemia / Chronic Phase of Disease / Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable / Recurrent Disease1
1, 2CompletedTreatmentAdult Acute Basophilic Leukemia / Adult Acute Eosinophilic Leukemia / Adult 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) / Childhood Myelodysplastic Syndromes / Chronic Myelomonocytic Leukemia / De Novo Myelodysplastic Syndromes / Refractory Anemia With Excess Blasts / Refractory Anemia With Excess Blasts in Transformation / Secondary Acute Myeloid Leukemia / Secondary Myelodysplastic Syndromes / Untreated Adult Acute Myeloid Leukemia1
1, 2CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma / Recurrent Adult Brain Tumor1
1, 2CompletedTreatmentAdult Solid Neoplasm / Inflammatory Breast Carcinoma / Male Breast Carcinoma / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer1
1, 2CompletedTreatmentCancer, Breast / Male Breast Cancer / Stage II Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer1
1, 2CompletedTreatmentGlioblastoma Multiforme1
1, 2CompletedTreatmentRecurrent Breast Carcinoma / Stage IV Breast Cancer1
1, 2CompletedTreatmentUntreated Childhood Brain Stem Glioma1
1, 2TerminatedTreatmentMultiple Myeloma (MM)1
1, 2TerminatedTreatmentRefractory Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma1
1, 2Unknown StatusTreatmentLeukemias / Myelodysplastic/Myeloproliferative Neoplasms1
2Active Not RecruitingTreatmentAnaplastic Large Cell Lymphoma / Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue / Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma / Nodal Marginal Zone Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Non-Hodgkin Lymphoma / Recurrent Small Lymphocytic Lymphoma / Splenic Marginal Zone Lymphoma1
2CompletedPreventionNeurofibromatosis Type I / Plexiform Neurofibroma1
2CompletedTreatmentAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome / Adult Acute Basophilic Leukemia / Adult Acute Eosinophilic Leukemia / Adult Acute Erythroid Leukemia (M6) / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5) / 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 Del(5q) / 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) / Cellular Diagnosis, Adult Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
2CompletedTreatmentAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome / Adult 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 Del(5q) / 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) / Secondary Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
2CompletedTreatmentAdenocarcinoma of the Pancreas / Stage II Pancreatic Cancer / Stage III Pancreatic 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 in Remission / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / 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 Leukemia / Untreated Adult Acute Myeloid Leukemia1
2CompletedTreatmentAdult 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(9;11)(p22;q23); MLLT3-MLL / Adult Acute Myeloid Leukemia Without Maturation / Adult Acute Myelomonocytic Leukemia / Adult Erythroleukemia / Adult Pure Erythroid Leukemia / Alkylating Agent-Related Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
2CompletedTreatmentAdult Acute Myeloid Leukemia in Remission / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / 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 / Secondary Myelodysplastic Syndromes1
2CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma1
2CompletedTreatmentBladder Cancers1
2CompletedTreatmentBladder Cancers / Transitional Cell Cancer of the Renal Pelvis and Ureter1
2CompletedTreatmentBrain and Central Nervous System Tumors1
2CompletedTreatmentCancer, Breast2
2CompletedTreatmentChildhood High-grade Cerebral Astrocytoma / Childhood Oligodendroglioma / Recurrent Childhood Brain Stem Glioma / Recurrent Childhood Cerebellar Astrocytoma / Recurrent Childhood Cerebral Astrocytoma / Recurrent Childhood Medulloblastoma / Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor / Recurrent Childhood Visual Pathway and Hypothalamic Glioma1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentEssential Thrombocythemia (ET) / Polycythemia Vera (PV) / Primary Myelofibrosis1
2CompletedTreatmentEstrogen Receptor-Positive Breast Cancer / Recurrent Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentGlioblastoma Multiforme1
2CompletedTreatmentInflammatory carcinoma of the breast / Stage II Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer1
2CompletedTreatmentJuvenile Myelomonocytic Leukemia1
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2CompletedTreatmentLeukemia, Nonlymphocytic, Acute1
2CompletedTreatmentLung Cancers2
2CompletedTreatmentMalignant Neoplasm of Pancreas2
2CompletedTreatmentMultiple Myeloma (MM)1
2CompletedTreatmentMyelodysplastic Syndrome1
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentRecurrent Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentRecurrent Melanoma / Stage IV Melanoma2
2CompletedTreatmentStage IIIb Non-small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer1
2RecruitingTreatmentAdvanced Non-hematological Malignancies / HRAS Mutant Tumor / Squamous Head and Neck Cancer / Thyroid Cancers1
2RecruitingTreatmentLeukemia, Myelomonocytic, Chronic1
2RecruitingTreatmentMyelodysplastic Syndromes1
2RecruitingTreatmentPeripheral T-cell lymphoma unspecified refractory / Relapsed Peripheral T-Cell Lymphoma1
2RecruitingTreatmentTransitional Cell Carcinoma1
2TerminatedTreatmentMantle Cell Lymphoma (MCL)1
2TerminatedTreatmentNeoplasms, Breast1
2TerminatedTreatmentStage III Chronic Lymphocytic Leukemia / Stage IV Chronic Lymphocytic Leukemia / T-Cell Large Granular Lymphocyte Leukemia1
2WithdrawnTreatmentCancer, Breast1
2, 3CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
3Active Not RecruitingTreatmentAdult Acute Myeloid Leukemia / Adult Acute Myeloid Leukemia in Remission1
3CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1

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 Solubility0.000478 mg/mLALOGPS
logP4.77ALOGPS
logP4.69ChemAxon
logS-6ALOGPS
pKa (Strongest Basic)7.74ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area64.15 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity148.2 m3·mol-1ChemAxon
Polarizability50.16 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9963
Blood Brain Barrier+0.9369
Caco-2 permeable+0.6126
P-glycoprotein substrateNon-substrate0.573
P-glycoprotein inhibitor INon-inhibitor0.8624
P-glycoprotein inhibitor IINon-inhibitor0.742
Renal organic cation transporterNon-inhibitor0.7321
CYP450 2C9 substrateNon-substrate0.818
CYP450 2D6 substrateNon-substrate0.8465
CYP450 3A4 substrateSubstrate0.6936
CYP450 1A2 substrateInhibitor0.8831
CYP450 2C9 inhibitorNon-inhibitor0.5646
CYP450 2D6 inhibitorNon-inhibitor0.8978
CYP450 2C19 inhibitorNon-inhibitor0.7466
CYP450 3A4 inhibitorInhibitor0.7116
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6269
Ames testNon AMES toxic0.598
CarcinogenicityNon-carcinogens0.9073
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6789 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9942
hERG inhibition (predictor II)Inhibitor0.5288
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 linear diarylheptanoids. These are diarylheptanoids with an open heptane chain. The two aromatic rings are linked only by the heptane chain.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Diarylheptanoids
Sub Class
Linear diarylheptanoids
Direct Parent
Linear diarylheptanoids
Alternative Parents
Phenylquinolines / Phenylpyridines / Hydroquinolones / Hydroquinolines / Pyridinones / Aralkylamines / Chlorobenzenes / Aryl chlorides / N-substituted imidazoles / Heteroaromatic compounds
show 8 more
Substituents
Linear 1,7-diphenylheptane skeleton / Phenylquinoline / 4-phenylpyridine / Dihydroquinolone / Dihydroquinoline / Quinoline / Chlorobenzene / Halobenzene / Aralkylamine / Pyridinone
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Essential subunit of the farnesyltransferase complex. Catalyzes the transfer of a farnesyl moiety from farnesyl diphosphate to a cysteine at the fourth position from the C-terminus of several prote...
Gene Name
FNTB
Uniprot ID
P49356
Uniprot Name
Protein farnesyltransferase subunit beta
Molecular Weight
48773.2 Da
References
  1. Venkatasubbarao K, Choudary A, Freeman JW: Farnesyl transferase inhibitor (R115777)-induced inhibition of STAT3(Tyr705) phosphorylation in human pancreatic cancer cell lines require extracellular signal-regulated kinases. Cancer Res. 2005 Apr 1;65(7):2861-71. [PubMed:15805288]

Drug created on October 21, 2007 16:23 / Updated on November 09, 2017 03:49