PF-07284892 (ARRY-558) is a potent and orally active SHP2 inhibitor with an IC50 value of 21 nM. PF-07284892 decreases the expression of pERK.
PF-07284892 (100 nM; 4, 18 h) combines with lorlatinib (0-450 nM), binimetinib (0-160 nM) decreases the expression of pERK in H3122 lorR-06, VACO-432 cells[2].
PF-07284892 (10 mg/kg; p.o.) shows good oral bioavailability with F% of 85%, 94%, 102%, 64% for mouse, rat, dog, monkey, respectively[2].
References:
[1]. Abdayem P, et al. Ongoing progress in BRAF-mutated non-small cell lung cancer. Clin Adv Hematol Oncol. 2022 Nov;20(11):662-672.
[2]. Drilon A, et al. SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy. Cancer Discov. 2023 Jun 3:OF1-OF13.