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Details

Stereochemistry ABSOLUTE
Molecular Formula C27H22Cl2N4O
Molecular Weight 489.396
Optical Activity ( + )
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIPIFARNIB

SMILES

CN1C=NC=C1[C@@](N)(C2=CC=C(Cl)C=C2)C3=CC4=C(C=C3)N(C)C(=O)C=C4C5=CC=CC(Cl)=C5

InChI

InChIKey=PLHJCIYEEKOWNM-HHHXNRCGSA-N
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

HIDE SMILES / InChI

Molecular Formula C27H22Cl2N4O
Molecular Weight 489.396
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Tipifarnib is an oral farnesyltransferase (FTase) inhibitor which was developed by Janssen (J&J). Upon administration, tipifarnib inhibits FTase and thus suppresses the activity of downstream effectors. The drug reached phase III of clinical trials for such diseases as pancreatic cancer (terminated), colorectal cancer (terminated) and acute myeloid leukemia (in elderly patients).

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
7.9 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
634 ng/mL
300 mg single, oral
TIPIFARNIB plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
3.8 μg × h/mL
300 mg single, oral
TIPIFARNIB plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
3.66 h
300 mg single, oral
TIPIFARNIB plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
0.7%
TIPIFARNIB plasma
Homo sapiens

Doses

AEs

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
Acute myeloid leukemia: 600 mg orally twice a day should be administered for the first 21 consecutive days, in 28-day cycles. Colorectal cancer: 300 mg should be given twice daily orally for 21 days every 28 days. Pancreatic cancer: tipifarnib is given at 200 mg twice daily orally continuously in combination with gemcitabine (1,000 mg/m(2) intravenously weekly x 7 for 8 weeks, then weekly x 3 every 4 weeks).
Route of Administration: Oral
In Vitro Use Guide
Tipifarnib was added to different cancer cell lines at concentrations ranging from 0.5–500 nm in 3 ul of DMSO. Cells were allowed to proliferate to high saturation densities beyond confluence for 4–7 days. The lowest IC50s were: 9.5 nM for SU86.86 (pancreatic cancer cell line with K-Ras mutation), 1.7 nM for HT-1197 (bladder cancer cell line with H-Ras mutation), 3.2 nM for WM-115 (melnoma, wild type), 6.5 nM for NCI-H292 (lung cancer cell line, wild type) and 3.9 nM for A673 (Rhabdomyo-sarcoma cell line, wild type).
Substance Class Chemical
Record UNII
MAT637500A
Record Status Validated (UNII)
Record Version