Amuvatinib

Amuvatinib (also known as MP-470 or 850879-09-3), is a multi-targeted inhibitor of receptor tyrosine kinases that inhibits c-Kit, platelet-derived growth factor receptor α (PDGFRα), and c-Met (IC50s = 10, 40, and 81 nM, respectively). It inhibits growth and induces apoptosis in prostate cancer cell lines, with additive effects achieved when combined with erlotinib . Amuvatinib sensitizes cancer cells to radiation and chemotherapeutic compounds, in part by inhibiting homologous recombination.

MP-470 (Amuvatinib) is a potent and multi-targeted inhibitor of c-KitD816H, PDGFαV561D and Flt3D835Y with IC50 of 10 nM, 40 nM and 81 nM, respectively.

ChEBI: N-(1,3-benzodioxol-5-ylmethyl)-4-(4-benzofuro[3,2-d]pyrimidinyl)-1-piperazinecarbothioamide is a N-arylpiperazine.

Amivantamab is the first drug approved by the FDA for the treatment of patients with NSCLC and EGFR exon 20 insertion mutations.

c-KitD816H

Μechanisticly, amuvatinib inhibits tyrosine kinase receptor KIT through occupying its ATP binding domain (IC50 < 0.1 μM) and disrupts DNA repair through suppression of homologous recombination protein Rad51 as well as synergistic effects in combination with double stranded DNA damaging agents.

1. Effects of combining amuvatinib (MP-470) with DNA-damaging agents in osteosarcoma cell lines
2. Janssen submits supplemental biologics license application to the U.S. Food and Drug Administration seeking approval of RYBREVANT? (amivantamab-vmjw) in combination with chemotherapy for the first-line treatment of patients with locally advanced or metastatic EGFR exon 20 insertion mutation-positive non-small cell lung cancer. News release.
3. Raoul Tibes, Gil Fine, Gavin Choy, Sanjeev Redkar, Pietro Taverna, Aram Oganesian, Amarpao Sahai, Mohammad Azab and Anthony W. Tolcher. A phase I, first-in-human dose-escalation study of amuvatinib, a multi-targeted tyrosine kinase inhibitor, in patients with advanced solid tumors. Cancer Chemother Pharmacol (2013) 71: 463-471
4. Gavin Choy, Rajashree Joshi-Hangal, Aram Oganesian, Gil Fine, Scott Rasmussen, Joanne Collier, James Kissling, Amarpal Sahai, Mohammad Azab and Sanjeev Redkar. Saftety, tolerability, and pharmacokinetics of amuvatinib from three phase 1 clinical studies in healthy volunteers. Cancer Chemother Pharmacol (2012) 70: 183-190