SOS1

RMC-0331 is a potent and selective inhibitor of SOS1, designed for oral bioavailability. It effectively blocks RAS activation by disrupting the interaction between RAS and SOS1, making it a valuable tool compound for in vivo studies. This compound is suitable for exploring RAS signaling pathways and investigating therapeutic applications in cancer research.

SOS1-IN-14 is a potent and selective inhibitor of SOS1, demonstrating an IC50 value of 3.9 nM. This orally active compound is absorbed in the intestine through a P-glycoprotein-mediated efflux mechanism. SOS1-IN-14 is primarily utilized in research on KRAS-mutated cancers, showcasing superior tumor suppression capabilities compared to alternative therapies.

SAH-SOS1A TFA is a peptide-based inhibitor targeting the SOS1-KRAS protein interaction. It exhibits nanomolar affinity for both wild-type and various mutant KRAS forms, including G12D, G12V, G12C, G12S, and Q61H (EC50 = 106-175 nM). By directly disrupting nucleotide association, SAH-SOS1A TFA effectively impairs KRAS-driven cancer cell viability and inhibits the downstream ERK-MAPK phosphosignaling cascade, making it a valuable tool for research in cancer biology.

SOS1-IN-15 is a potent SOS1 inhibitor with an IC50 value of 5 nM, designed to specifically target and inhibit SOS1 activity. Its strong inhibitory effect makes it a promising candidate for research into KRAS-driven cancers, facilitating the understanding of oncogenic signaling pathways and development of targeted therapeutic strategies.

SOS1/EGFR-IN-1 is a dual-target inhibitor that specifically targets SOS1 and EGFR, demonstrating IC50 values of 42.13±1.55 nM and 1.01±0.04 nM, respectively. This compound effectively induces apoptosis and G1 phase cell cycle arrest, while reducing angiogenesis and cell migration. SOS1/EGFR-IN-1 exhibits significant antitumor activity in prostate cancer cells, with an IC50 of 0.45±0.03 μM, making it a valuable tool for research in cancer therapies.

RGT-018 is a potent, orally active SOS1 inhibitor that exhibits anti-tumor activity by blocking KRAS activation. By disrupting the SOS1–KRAS interaction, RGT-018 effectively inhibits cancer cell proliferation, making it a promising candidate for targeting KRAS-driven malignancies.

SOS1-IN-11 is a potent small-molecule inhibitor of SOS1, exhibiting an IC₅₀ value of 30 nM. It is used in research to disrupt the SOS1–KRAS interaction and modulate RAS signaling pathways in cancer models.

MRTX0902 is an orally active and potent SOS1 inhibitor, exhibiting an IC₅₀ of 46 nM (WO2021127429A1; Example 12-10). It is designed to disrupt the SOS1–KRAS interaction, making it a promising candidate for targeting KRAS-driven cancers.

SOS1-IN-22 is a selective inhibitor of the son of sevenless homolog 1 (SOS1), crucial for the formation of the KRAS-G12C/SOS1 complex with an IC50 value of 40.28 nM. This compound effectively reduces ERK phosphorylation levels, influencing downstream signaling pathways. SOS1-IN-22 is intended for research applications in cancer biology, particularly relevant to pancreatic carcinoma and appendiceal carcinoma.

SOS1-IN-8 is a selective inhibitor of the SOS1 protein, exhibiting IC50 values of 11.6 nM for the SOS1-G12D variant and 40.7 nM for the SOS1-G12V variant. This compound serves as a valuable tool in the study of SOS1-mediated signaling pathways and their implications in various cancers. Its potent inhibitory activity makes it suitable for investigating therapeutic strategies targeting oncogenic mutations associated with SOS1.

SOS1-IN-16 is a selective inhibitor of the SOS1 protein with an IC50 of 7.2 nM, making it a potent tool for studying SOS1-mediated signaling pathways. This compound exhibits inhibitory activity towards CYP3A4 when testosterone is utilized as a substrate, with an IC50 of 8.9 μM. SOS1-IN-16 is primarily applied in cancer research, facilitating the investigation of therapeutic strategies targeting SOS1-related oncogenic processes.

SOS1-IN-7 is a selective inhibitor targeting SOS1, demonstrating potent activity with IC50 values of 20 nM for the SOS1-G12D mutant and 67 nM for the SOS1-G12V variant. This compound effectively disrupts SOS1-mediated signaling pathways, making it a valuable tool for investigating the roles of SOS1 in cancer biology. Its application in research may facilitate the development of therapeutic strategies against tumors driven by mutant RAS signaling.

SOS1-IN-25 is a selective inhibitor of the SOS1 protein, effectively disrupting the formation of the KRASG12C/SOS1 complex with an IC50 of 11.11 nM. This compound demonstrates a dose-dependent reduction in phosphorylated ERK levels, indicating its potential to modulate downstream signaling pathways. SOS1-IN-25 is suitable for research focused on leukemia and other cancers associated with aberrant KRAS signaling.

SOS1-IN-3 is a potent inhibitor of SOS1 (son of sevenless homolog 1) with an IC50 value of 5 nM. This compound exhibits significant anticancer activity, making it a valuable tool for research in cancer biology. Its specificity for SOS1 allows for potential applications in studying the molecular mechanisms of cancer signaling pathways.

SOS1-IN-12 is a highly potent inhibitor of son of sevenless homolog 1 (SOS1), exhibiting a Ki value of 0.11 nM for SOS1 and an IC50 of 47 nM for phosphorylated ERK (pERK). This compound serves as a valuable tool for investigating the role of SOS1 in signaling pathways associated with cancer biology, enabling researchers to explore its potential in anticancer studies and therapeutic applications.

SOS1-IN-10 is a selective inhibitor of SOS1, exhibiting a potent inhibitory effect with an IC50 value of 13 nM specifically targeting the KRAS G12C-SOS1 interaction. This compound is valuable for research studying the role of SOS1 in oncogenic signaling pathways, particularly in cancer models driven by KRAS mutations. Its use can facilitate investigations into therapeutic strategies aimed at modulating RAS-dependent pathways.

HH0043 is a potent SOS1 inhibitor with an IC50 value of 5.8 nM. This orally active compound exhibits significant inhibition of the SOS1 protein, which plays a critical role in Ras signaling pathways. HH0043 is utilized in cancer research to explore therapeutic strategies targeting oncogenic signaling mechanisms.

NSC-658497 is a potent inhibitor of the Ras guanine nucleotide exchange factor SOS1. It competitively binds to SOS1, thereby effectively inhibiting the SOS1-Ras interaction and reducing SOS1's guanine nucleotide exchange factor activity in a dose-dependent manner. This compound has demonstrated significant efficacy in suppressing Ras signaling pathways, ultimately leading to a reduction in associated cell proliferation. NSC-658497 is valuable for research in cancer biology and signaling modulation.

SOS1-IN-4 is a potent inhibitor of SOS1, exhibiting an IC50 of 56 nM for the KRAS-C12C/SOS1 interaction. This compound is instrumental in studies investigating the role of SOS1 in RAS signaling pathways. Its application is significant in cancer research, particularly in models where KRAS mutations contribute to tumorigenesis.

SOS1-IN-2 is a potent inhibitor of SOS1, demonstrating an IC50 value of 5 nM. Its primary mechanism involves the inhibition of SOS1-mediated signaling pathways, making it a valuable tool in cancer research. This compound is suitable for studies focused on tumor biology and the exploration of therapeutic strategies targeting the SOS1 pathway.

SOS1-IN-5 is a potent inhibitor of SOS1, a critical component in RAS signaling pathways. This pyrimidobicyclic derivative disrupts the interaction between RAS and SOS1, effectively blocking KRAS activation and offering broad-spectrum inhibition of KRAS activity. SOS1-IN-5 is intended for use in cancer research, providing valuable insights into therapeutic strategies targeting KRAS-driven malignancies.

SOS1/KRAS-IN-1 is a potent inhibitor targeting the SOS1/KRAS signaling pathway, critical in various cancers. This compound effectively disrupts SOS1-mediated activation of KRAS, providing valuable insights into SOS1/KRAS-mediated diseases. It is suitable for research applications investigating oncogenic signaling and potential therapeutic strategies against KRAS-driven malignancies.

SOF-436 is a selective KRAS inhibitor that targets SOS1-mediated nucleotide exchange, exhibiting an IC50 of 60 μM. Additionally, it effectively disrupts the interaction between KRAS and the effector protein RAF. This compound is primarily utilized in cancer research, providing insights into KRAS-driven oncogenic pathways.

SOS1-IN-9 is a selective inhibitor of SOS1, demonstrating an IC50 of 116.5 nM for the SOS1-KRAS G12C complex. This compound plays a crucial role in inhibiting SOS1-mediated signaling pathways, making it a valuable tool for research into KRAS-driven cancers. Its application extends to studies aimed at elucidating the mechanisms of oncogenic signaling and developing targeted therapeutic strategies.

SOS1-IN-6 is a selective inhibitor of SOS1, demonstrating potent activity with IC50 values of 14.9 nM for the SOS1-G12D variant and 73.3 nM for SOS1-G12V. This compound is primarily utilized in research focused on RAS signaling pathways and cancer biology, offering potential insights into therapeutic strategies targeting oncogenic mutations. Its effectiveness makes SOS1-IN-6 a valuable tool for investigating the modulation of SOS1-related cellular processes.

SAH-SOS1A is a peptide-based inhibitor targeting the SOS1/KRAS protein interaction. It binds with nanomolar affinity (EC50 = 106-175 nM) to both wild-type and various mutant forms of KRAS, including G12D, G12V, G12C, G12S, and Q61H. By directly obstructing nucleotide association, SAH-SOS1A interferes with KRAS-driven cancer cell viability and inhibits the ERK-MAPK phosphosignaling cascade downstream of KRAS, making it a valuable tool for cancer research and therapeutic exploration.

SOS1-IN-13 is a potent inhibitor of son of sevenless homolog 1 (SOS1), exhibiting IC50 values of 6.5 nM for SOS1 and 327 nM for phosphorylated extracellular signal-regulated kinase (pERK). This compound is valuable in anticancer research, providing insights into the role of SOS1 in tumorigenesis and signaling pathways associated with cell proliferation and survival. Its high selectivity allows for targeted studies of SOS1-mediated mechanisms in various cancer models.

KRAS G12C inhibitor 56 is a selective SOS1 inhibitor that exhibits potent inhibitory activity with an IC50 of 1.6 nM. This compound is relevant for cancer research, particularly in studies targeting KRAS-driven malignancies, and may provide insights into therapeutic strategies for tumors harboring KRAS G12C mutations. Researchers can leverage this inhibitor to explore the biochemical mechanisms of cell signaling and proliferation linked to KRAS activation.

SOS1-IN-1 is a SOS1 inhibitor.

BAY-293 is a potent, cell-active SOS1 inhibitor that disrupts the KRAS-SOS1 interaction with IC50 of 21 nM.

BI-3406 (SOS1-IN-2) is a Son of Sevenless 1 (SOS1) inhibitor with an IC50 of 6 nM.

UC-857993 is a selective inhibitor of the SOS1-Ras interaction, effectively suppressing its catalytic activity with a Kd of 14.7 μM (His6-SOS1cat). This compound also inhibits ERK and Ras activation, demonstrating significant capabilities in reducing the proliferation of mouse embryonic fibroblasts (MEFs). UC-857993 is valuable for research into cancer biology and signaling pathways involving Ras.

UC-773587 is a selective inhibitor of SOS1 catalytic activity. By specifically binding to the catalytic site of SOS1, it inhibits nucleotide exchange with an IC50 of 4.5 μM, while demonstrating minimal interaction with HRas and ITSN. This compound is valuable for research into signaling pathways and has potential applications in the study of prostate cancer.

SOS1-IN-21 is a potent inhibitor of son of Sevenless 1 (SOS1) with an IC50 of 15 nM. As a guanine nucleotide exchange factor (GEF), SOS1 plays a critical role in the activation of KRAS by promoting GDP-GTP exchange. SOS1-IN-21 demonstrates significant antiproliferative effects, exhibiting IC50 values of 16 nM in NCI-H358 and 17 nM in Mia Paca-2 cell lines. Additionally, it shows substantial antitumor activity in the Mia Paca-2 xenograft model, making it a valuable tool for research on KRAS mutant tumors, including pancreatic cancer.