17,19-Metheno-1H,5H-cyclopent[5,6][1,4]oxazino[3,4-i]pyrazolo[4,3-f]pyrido[3,2-l][1,4,8,10]oxatriazacyclotridecin-14(11H)-one, 7-fluoro-2,3,3a,12,13,20a-hexahydro-11-methyl-, (3aS,11R,20aR)-

Biological Activity

TPX-0046 is a novel RET/SRC inhibitor with a mean IC50 of 17 nM for RETG810R in Ba/F3 cell proliferation assay. TPX-0046 is a new type of RET/SRC inhibitor and potent against a range of RET fusions and mutations including solvent front mutations (SFMs)-mediated resistance. In Ba/F3 RET engineered cells with SFMs proliferation test, the average IC50 is 1-17 nM.[2] TPX-0046 demonstrates marked anti-tumor efficacy in vivo in multiple RET-driven cancer cell-derived and patient-derived xenograft tumor models.[2]

References

[1] Noura J Choudhury, Alexander Drilon. Transl Lung Cancer Res. 2020 Dec;9(6):2571-2580. [2] Alexander E Drilon, et al. Journal of Clinical. 2020 May; 38(15_suppl): 3616.