Stereochemistry | ABSOLUTE |
Molecular Formula | C27H22Cl2N4O |
Molecular Weight | 489.396 |
Optical Activity | ( + ) |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
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
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 |
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
Doses
AEs
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Drug as victim
PubMed
Sample Use Guides
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
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).