Drug intelligence / Profile preview

sitravatinib + rifampin

Development stage
Unknown
Lead developer
Bristol Myers Squibb
Modality
Small Molecules
Administration
Oral
01

Overview

**Sitravatinib + rifampin** is a combination of two drugs: sitravatinib, a small molecule oral multi-kinase inhibitor with antineoplastic (anticancer) activity, and rifampin, an antibiotic of the rifamycin class known for its use in tuberculosis and as a potent inducer of several cytochrome P450 enzymes, including CYP3A4. Sitravatinib targets multiple receptor tyrosine kinases (RTKs) implicated in tumor growth and the immunosuppressive tumor microenvironment, specifically inhibiting VEGFR, TAM family receptors (TYRO3, AXL, MERTK), MET, KIT, DDR2, PDGFR, RET, TRK, and Eph family kinases. Rifampin is not used as an oncologic therapy but is relevant pharmacologically for its strong induction of CYP3A4, which can significantly reduce plasma levels of other drugs metabolized by this enzyme, including sitravatinib. The combination is not an approved therapy; it may be studied in drug-drug interaction research or for pharmacokinetic modulation. There are no clinical trials or clinical uses specifically for this combination as therapy; rather, the relevance of this combination is as an example of a clinically significant drug-drug interaction, where rifampin can decrease efficacy of sitravatinib by increasing its metabolism[3].

02

Targets

AXL (AXL receptor tyrosine kinase)MET (Mesenchymal-epithelial transition factor receptor)KIT (c-KIT proto-oncogene receptor tyrosine kinase)VEGFR2 (Vascular endothelial growth factor receptor 2)CYP3A4 (Cytochrome P450 3A4)PDGFR (PDGFR family)Trk (Trk receptor family)DDR1 (Discoidin domain receptor 1)RET (Rearranged during transfection receptor tyrosine kinase)FLT3 (Fms related receptor tyrosine kinase 3)DDR2 (Discoidin domain receptor tyrosine kinase 2)

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