RET-IN-4 is a potent, selective and orally active RET inhibitor with IC 50 s of 1.29 nM, 1.97 nM, and 0.99 nM for RET (WT) , RET (V804M) , and RET (M918T) , respectively. RET-IN-4 exhibits better kinases selectivity against JAK2 (IC 50 of 4.4 nM) and FLT3 (IC 50 of 30.8 nM). RET-IN-4 has anticancer effects.

The proliferation of Ba/F3 cells transformed with NSCLC related KIF5B-RET fusion is effectively suppressed by RET-IN-4 (compound 9) (IC 50 of 19 nM). RET-IN-4 displays less ‘off-target’ effects than BLU-667[1].

RET-IN-4 (compound 9; p.o.; 10-20 mg/kg; p.o.; daily; for 10 days) treatment represses tumor growth driven by KIF5B-RET-Ba/F3 cells in a dose-dependent manner[1]. Animal Model: Immunodeficient nude/nude mice bearing KIF5B-RET Ba/F3 cells[1]Dosage: 10 mg/kg, 20 mg/kg Administration: p.o.; daily; for 10 days Result: The tumor growth was remarkably suppressed.

2436473-55-9

C27H31FN10O2

546.6

RET-IN-4

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years