SOS1 Inhibitor

BI-3406 (compound I-6) is an orally active, highly potent and selective inhibitor of the interaction between KRAS and Son of Sevenless 1 (SOS1) with an IC₅₀ of 6 nM. BI-3406 potently reduces the formation of GTP-loaded KRAS, and inhibits MAPK pathway signaling. BI-3406 has anticancer activity.

MRTX0902 is a potent, selective, brain-penetrant, and orally active SOS1 inhibitor with a K_i of 1.9 nM. MRTX0902 disrupts the SOS1:KRASG12C protein-protein interaction (PPI). MRTX0902 can be used in research on pancreatic ductal adenocarcinoma.

BAY-293, a valuable chemical probe, blocks RAS activation via disruption of the KRAS-SOS1 interaction with an IC₅₀ of 21 nM. BAY-293 is a potent inhibitor of Son of Sevenless 1 (SOS1). SOS1 is the guanine nucleotide exchange factor (GEF) and activator of RAS.

RMC-0331 (RM-023) is a potent, selective and orally bioavailable SOS1 inhibitor. RMC-0331 is an in vivo tool compound that blocks RAS activation via disruption of the RAS-SOS1 interaction.

SAH-SOS1A TFA is a peptide-based SOS1/KRAS protein interaction inhibitor. SAH-SOS1A TFA binds to wild-type and mutant KRAS (G12D, G12V, G12C, G12S, and Q61H) with nanomolar affinity (EC₅₀=106-175 nM). SAH-SOS1A TFA directly and independently blocks nucleotide association. SAH-SOS1A TFA impairs KRAS-driven cancer cell viability and exerts its effects by on-mechanism blockade of the ERK-MAPK phosphosignaling cascade downstream of KRAS.

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 (HY-125817).

BTX-7312 is a cereblon-based SOS1 bifunctional degrader and a molecular glue. BTX-7312 reduces downstream signaling markers pERK and pS6 and shows antiproliferative activity in various KRAS-mutated cells.

RGT-018 is a potent and orally active SOS1 inhibitor with anti-tumor effects. RGT-018 exerts anti-cancer cell proliferation activity by inhibiting KRAS activation.

SOS1-IN-11 is a potent SOS1 inhibitor with an IC₅₀ value of 30 nM.

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

NSC-70220 is a selective and allosteric SOS1 inhibitor. NSC-70220 inhibits allosteric site activation, and partially inhibited catalytic site activation. NSC-70220 has an anticancer effect.

SOS1 Human Pre-designed siRNA Set A contains three designed siRNAs for SOS1 gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.

BI-0474 is a potent KRAS^G12C inhibitor with an IC₅₀ value of 7.0 nM for the GDP-KRAS::SOS1 protein-protein interaction. BI-0474 exhibits good anti-proliferative activity against NCI-H358 cells carrying the G12C mutation. BI-0474 also shows good anti-tumour activity in non-small cell lung cancer xenograft models.

SOS1/EGFR-IN-1 (compound SE-9) is a dual-target inhibitor for the prostate cancer. SOS1/EGFR-IN-1 inhibits effectively SOS1(IC₅₀=42.13±1.55 nM) and EGFR(IC₅₀=1.01±0.04 nM) by inhibiting their downstream effector molecules. SOS1/EGFR-IN-1 induces apoptosis and G1 phase cell cycle arrest, reducing angiogenesis and migration. SOS1/EGFR-IN-1 shows significant antitumor effects in prostate cancer cells PC-3 (IC₅₀=0.45±0.03 μM).

DCAI is a KRas inhibitor with a K_d value of 1.1 mM. DCAI directly binds to the Ras protein and competitively inhibits SOS-mediated nucleotide release (IC₅₀ = 155 μM) and exchange reaction (IC₅₀ = 342 μM). DCAI binds to the pocket at the Ras-SOS interface and blocks the formation of the Ras-SOS complex intermediate by impeding salt bridge formation through steric hindrance and the induction of Ras conformational changes. DCAI is used in the study of wild-type and mutant Ras tumors.

E8431 is a DCSTAMP antagonist with an IC₅₀ value of 775.8 nM for osteoclastogenesis. E8431 selectively binds to the endoplasmic reticulum domain of DCSTAMP, disrupts its interaction with RAP1B, and inhibits downstream cytoskeleton rearrangement mediated by the RAP1-RAC1 signaling pathway, thereby impeding osteoclast precursor fusion, suppressing bone resorption, and stimulating PDGFBB secretion to promote osteogenesis and angiogenesis. E8431 can be used in the research of osteoporosis.

(S)-BAY-293 is a negative control of BAY 293. BAY 293 is a potent KRAS-SOS1 interaction inhibitor.

SOS1-IN-8 is a potent SOS1 inhibitor with IC₅₀s of 11.6 and 40.7 nM for SOS1-G12D and SOS1-G12V, respectively (WO2022017339A1, compound 2).

SOS1-IN-16 (Comp 54) is a selective inhibitor of SOS1 with an IC₅₀ of 7.2 nM. SOS1-IN-16 has inhibitory activity of CYP3A4 when using testosterone as a substrate, with an IC₅₀ of 8.9μM. SOS1-IN-16 can be used for cancer research.

SOS1-IN-7 (compound 18-p1) is a potent SOS1 inhibitor with IC₅₀s of 20 and 67 nM for SOS1-G12D and SOS1-G12V, respectively.