| Stereochemistry | ACHIRAL |
| Molecular Formula | C9H11ClN4O2 |
| Molecular Weight | 242.662 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
ClC1=C(CN2CCCC2=N)NC(=O)NC1=O
InChI
InChIKey=QQHMKNYGKVVGCZ-UHFFFAOYSA-N
InChI=1S/C9H11ClN4O2/c10-7-5(12-9(16)13-8(7)15)4-14-3-1-2-6(14)11/h11H,1-4H2,(H2,12,13,15,16)
| Molecular Formula | C9H11ClN4O2 |
| Molecular Weight | 242.662 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
Tipiracil is a thymidine phosphorylase inhibitor, that used for the treatment of patients with metastatic colorectal cancer. Tipiracil is used in combination with trifluridine as Lonsurf. Trifluridine is incorporated into DNA via phosphorylation, ultimately inhibiting cell proliferation. Tipiracil increases systemic exposure of trifluridine when coadministered. Lonsurf has recently been approved for the treatment of adult patients with metastatic colorectal cancer (mCRC) who are refractory to or are not considered candidates for, current standard chemotherapy and biological therapy in the EU and USA and in unresectable advanced or recurrent CRC in Japan. The approved regimen of oral twice-daily Lonsurf significantly improved overall survival and progression-free survival and was associated with a significantly higher disease control rate than placebo when added to best supportive care in the multinational, pivotal phase III trial (RECOURSE) and a phase II Japanese trial. Trifluridine/tipiracil was associated with an acceptable tolerability profile, with adverse events generally being managed with dose reductions, temporary interruptions in treatment or administration of granulocyte-colony
stimulating factor. The most common grade 3–4 adverse events (>10 %) were anemia, neutropenia, thrombocytopenia, and leukopenia.
CNS Activity
Originator
Approval Year
Cmax
AUC
T1/2
Doses
AEs
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Sourcing
PubMed
Patents
Sample Use Guides
In combination with trifluridine, 35 mg/m2 up to a maximum of 80 mg per dose (based on the trifluridine component) orally twice daily within one hour of completion of morning and evening meals on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until disease progression or unacceptable toxicity.
Route of Administration:
Oral
HCT 116, HCT-15, and HT-29 cells were seeded at appropriate concentrations in duplicates in six-well plates. Twenty-four hours after plating, the cells were treated with the trifluridine (FTD 2 mkM or 4 mkM), or IR alone, or the combination of both using the RX-650 CABINET X-Ray system (Faxitron Xray Corp., Wheeling, IL, USA) with 3.4 Gy/min for 0.6-2.4 min. Ten to 12 days after plating, cells were fixed with 20% glutaraldehyde, stained with 0.05% crystal violet, and the number of colonies containing at least 50 cells was determined. Trifluridine enhances the efficacy of IR.
