SOS1-IN-15

SOS1-IN-15 (Compound 37) is an orally active SOS1 inhibitor with an IC50 of 5 nM. SOS1-IN-15 is a promising drug candidate for the research of KRAS-driven cancer[1].

Research Areas >> Cancer

Signaling Pathways >> GPCR/G Protein >> Ras

SOS1:5 nM (IC50)

SOS1-IN-15 (Compound 37) (0.1 nM-0.1 mM; 72 h) displays prominent inhibitory activities in Mia-paca-2 cancer cells (IC50 = 178 ± 42 nM)[1]. SOS1-IN-15 has a limited inhibition of CYP and hERG[1]. Cell Proliferation Assay[1] Cell Line: Mia-paca-2 pancreas cancer cells Concentration: 0.1 nM-0.1 mM Incubation Time: 72 h Result: Inhibited the proliferation with an IC50 of 178 ± 42 nM.

SOS1-IN-15 (Compound 37) (50 mg/kg; p.o.; daily for 22 days) inhibits tumor volume in mice[1]. Animal Model: BALB/c nude mice bearing Mia-paca-2 pancreas tumors[1] Dosage: 50 mg/kg Administration: Oral administration, daily for 22 days Result: Showed 49% tumor inhibition. No animal mortality and significant difference in the mice’s body weight were observed during the study period. Animal Model: Male CD-1 Mice[1] Dosage: 20 mg/kg Administration: Oral administration (Pharmacokinetic Analysis) Result: In Vivo Pharmacokinetic Properties of the Compounds in Male CD-1 Micea T1/2 (h) Tmax (h) Cmax (ng/mL) AUC (ng⋅h/mL) MRT (h) Kel (h-1) SOS1-IN-15 11.4 3.67 1550 9900 4.19 0.25 aCompounds (20 mg/kg) were P.O. dosed in a mixture of 63% water + 30% PEG +5 % DMSO + 2% Tween 80 in male ICR mice (n = 3). Abbreviations: T1/2, elimination half-life; Tmax, plasma peak time after administration; Cmax, maximum plasma concentration; AUC, area under concentration-time curve. MRT, mean residence time; Kel, elimination rate constant.

[1]. Zhang S, et al. Design and Structural Optimization of Orally Bioavailable SOS1 Inhibitors for the Treatment of KRAS-Driven Carcinoma. J Med Chem. 2022 Nov 17.