Details of the Drug

General Information of Drug (ID: DMF30HL)

Drug Name
Zarnestra
Synonyms
JAN; Tipifarnib; Tipifarnib [USAN]; R 115777; R115777; R-11577; R-115777; Tipifarnib (USAN/INN); Zarnestra, IND 58359, R115777, Tipifarnib; (R)-6-(Amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone; (R)-R115777; 2 (1H))-Quinolinone,6-(amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-, 2(1H)-quinolinone; 6-[(R)-amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2(1H)-one; 6-[(R)-amino-(4-chlorophenyl)-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2-one; 6-[(S)-AMINO(4-CHLOROPHENYL)(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]-4-(3-CHLOROPHENYL)-1-METHYLQUINOLIN-2(1H)-ONE
Indication
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Phase 3 [1]
Chronic myelogenous leukaemia 2A20.0 Phase 2 [2]
Human papillomavirus infection 1A9Y Phase 2 [2]
Myelodysplastic syndrome 2A37 Phase 2 [2]
Peripheral T-cell lymphoma 2A90.C Phase 2 [2]
Colorectal cancer 2B91.Z Phase 1/2 [3]
Pancreatic cancer 2C10 Phase 1/2 [3]
⏷ Show the Full List of Indication(s)
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 489.4
Logarithm of the Partition Coefficient (xlogp) 4.1
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 3
Chemical Identifiers
Formula
C27H22Cl2N4O
IUPAC Name
6-[(R)-amino-(4-chlorophenyl)-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2-one
Canonical SMILES
CN1C=NC=C1[C@@](C2=CC=C(C=C2)Cl)(C3=CC4=C(C=C3)N(C(=O)C=C4C5=CC(=CC=C5)Cl)C)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
InChIKey
PLHJCIYEEKOWNM-HHHXNRCGSA-N
Cross-matching ID
PubChem CID
159324
ChEBI ID
CHEBI:141969
CAS Number
192185-72-1
DrugBank ID
DB04960
TTD ID
D07NPS
VARIDT ID
DR00414
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Farnesyl protein transferase (Ftase) TTXQKM3 FNTA_HUMAN ; FNTB_HUMAN Modulator [4]
Geranyltranstransferase (FDPS) TTIKWV4 FPPS_HUMAN Inhibitor [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Drug Response [5]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Gene/Protein Processing [6]
GTP-binding protein Rheb (RHEB) OTFLTSEC RHEB_HUMAN Gene/Protein Processing [7]
GTPase HRas (HRAS) OTWQN0DP RASH_HUMAN Biochemical Pathways [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Acute myeloid leukaemia
ICD Disease Classification 2A60
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Farnesyl protein transferase (Ftase) DTT FNTB; FNTA 5.43E-01 -0.1 -0.4
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 ClinicalTrials.gov (NCT00093990) Tipifarnib Versus Best Supportive Care in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML). U.S. National Institutes of Health.
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
4 Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia. Biologics. 2008 Sep;2(3):491-500.
5 Pharmacogenetics of tipifarnib (R115777) transport and metabolism in cancer patients. Invest New Drugs. 2004 Aug;22(3):285-9.
6 Genetic disruption of the PI3K regulatory subunits, p85, p55, and p50, normalizes mutant PTPN11-induced hypersensitivity to GM-CSF. Haematologica. 2012 Jul;97(7):1042-7. doi: 10.3324/haematol.2011.046896. Epub 2012 Feb 7.
7 Ras homologue enriched in brain is a critical target of farnesyltransferase inhibitors in non-small cell lung cancer cells. Cancer Lett. 2010 Nov 1;297(1):117-25. doi: 10.1016/j.canlet.2010.05.004.
8 Farnesyltransferase inhibitor R115777 (Zarnestra, Tipifarnib) synergizes with paclitaxel to induce apoptosis and mitotic arrest and to inhibit tumor growth of multiple myeloma cells. Blood. 2005 Jun 15;105(12):4759-66. doi: 10.1182/blood-2004-11-4307. Epub 2005 Feb 22.