SOS1-IN-14 is a potent, selective and orally active SOS1 inhibitor with an IC50 value of 3.9 nM. SOS1-IN-14 can be absorbed in the intestine via a P-glycoprotein-mediated efflux mechanism. SOS1-IN-14 can be used to research KRAS-mutated cancers. SOS1-IN-14 has better potent tumor suppression than BI-3406 [1].
SOS1-IN-14 (compound 13c) exhibits cellular SOS1 inhibition with an IC50 of 21 nM[1].
SOS1-IN-14 has certain inhibition for CYP2D6, CYP2C9, CYP2C8 and CYP3A4 with IC50s of 2.5 μM, 6.5 μM, 43.3 μM and 54.3 μM, respectively, indicating that it has a certain risk of drug-drug interaction[1].
SOS1-IN-14 (50 mg/kg; p.o.; qd) exhibits 83.0% tumor suppression in Mia-paca-2 pancreas xenograft mice tumor models[1].
SOS1-IN-14 shows a favorable pharmacokinetic profile with a bioavailability of 86.8% in beagles[1].
Pharmacokinetic Parameters of SOS1-IN-14 (compound 13c) in ICR mice, Sprague-Dawley rats and Beagle dogs[1].
| ICR Mice | Sprague-Dawley Rats | Beagle Dogs | |||
| Administration | p.o., 50 mg/kg | i.v., 2 mg/kg | p.o., 10 mg/kg | i.v., 2 mg/kg | p.o., 20 mg/kg |
| Tmax (h) | 0.5 | 0.08 | 3 | 0.08 | 2 |
| T1/2 (h) | 4.61 | 1.17 | 2.32 | 3.83 | 6.68 |
| Cmax (μg/mL) | 2670 | 1261 | 265 | 568 | 1840 |
| AUC0-24 (ng/mL.h) | 32300 | 970 | 1683 | 2962 | 25725 |
| CL (mL/min/kg) | / | 2068 | / | 11.3 | / |
| Vss (L/kg) | / | 2126 | / | 3.88 | / |
| F (%) | / | / | 34.5 | / | 86.8 |
| Kel (h-1) | 0.265 | / | / | / | / |
| MRT (h) | 4.67 | / | / | / | / |
| Animal Model: | BALB/c nude mice (KRAS G12C variant Mia-paca-2 xenograft models)[1] |
| Dosage: | 50 mg/kg |
| Administration: | p.o.; q.d., for 21 days |
| Result: | Exhibited 83.0% tumor suppression. Showed better potent tumor suppression than BI-3406 . |