Ras Inhibitor

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

SIAIS562055 is a potent cereblon-based SOS1 PROTAC with a K_d of 95.9 nM. SIAIS562055 exhibits sustained degradation of SOS1 and inhibition of downstream ERK pathways. SIAIS562055 effectively blocked the binding of KRAS^G12C or KRAS^G12D to SOS1, with the IC₅₀ values of 95.7 nM and 134.5 nM, respectively. SIAIS562055 exhibits potent anticancer activity.

RAS-IN-5 (Example 2) is a RAS inhibitor. RAS-IN-5 significantly inhibits the interaction between RAF1 and active KRAS mutant protein or HRAS WT protein. RAS-IN-5 significantly inhibits the cell viability of KRAS, NRAS, and EGFR mutant cells. RAS-IN-5 can be used in the research of colorectal cancer, liver cancer, and non-small cell lung cancer.

Avicin G is a sphingomyelinase inhibitor and plasma membrane disruptor. Avicin G inhibits the enzymatic activities of neutral sphingomyelinases (SMPD2/3) and acid sphingomyelinase (SMPD1), elevates intracellular sphingomyelin levels, and alters the distribution of sphingomyelin. Avicin G interferes with the lateral segregation of GTP- and GDP-bound H-Ras, inhibits the signal output of oncogenic K-Ras and H-Ras, reduces the phosphorylation of ERK and Akt, increases lysosomal pH, and inhibits the endocytic recycling of epidermal growth factor receptor. Avicin G can be used in research related to pancreatic ductal adenocarcinoma and non-small cell lung cancer.

MRTX849-amide-C4-(o)-carborane is a KRAS^G12C inhibitor with mutation selectivity for cells expressing KRAS^G12C. MRTX849-amide-C4-(o)-carborane shows low intrinsic cytotoxicity in cancer cells. MRTX849-amide-C4-(o)-carborane covalently binds to Cys12 of KRAS^G12C, recruits Hsp70, promotes ubiquitination, and induces proteasome-dependent degradation of the target protein. MRTX849-amide-C4-(o)-carborane inhibits the activity of the downstream ERK signaling pathway and induces apoptosis signaling in cancer cells. MRTX849-amide-C4-(o)-carborane is applicable for the research of KRAS^G12C-positive cancers.

SOS1-IN-13 is a potent son of sevenless homolog 1 (SOS1) inhibitor with IC₅₀s of 6.5 nM and 327 nM for SOS1 and pERK, respectively. SOS1-IN-13 can be used for researching anticancer.

KRAS inhibitor-11 (compound 12) is a KRAS inhibitor.

KRAS G12C inhibitor 26 is a KRAS G12C inhibitor with antitumor effects (WO2021109737).

KRAS G12C-IN-72 (Example 571) is a KRAS G12C inhibitor. KRAS G12C-IN-72 can be used as a target protein ligand to synthesize PROTACs, such as KRAS degrader-1 (HY-153880). KRAS G12C-IN-72 can be used in cancer research.

KRASG12D-IN-4 (example 38) is a KRas^G12D inhibitor with an IC₅₀ of 3.3 nM. KRASG12D-IN-4 inhibits proliferation of pancreatic cancer ASPC-1 cells with an IC₅₀ of 12 nM.

KRAS G12D-IN-34 (Compound 13) is a KRAS (G12D) inhibitor with IC₅₀ values for KRAS (G12D) and KRAS (WT) of 1.05 nM and 1.59 μM respectively. KRAS G12D-IN-34 can be used for research on non-small cell lung cancer.

KRAS inhibitor-32 (compound 139A) is a KRAS inhibitor. KRAS inhibitor-32 can be used in anti-cancer research.

KRAS G12C inhibitor 41 is a potent inhibitor of KRAS G12C. The Ras family of proteins is an important intracellular signaling molecule that plays an important role in growth and development. KRAS G12C inhibitor 41 has the potential for the research of KRAS G12C-mediated cancer (extracted from patent WO2021129824A1, compound 121).

DPAP is a p-ERK1/2 inhibitor with an IC₅₀ of 7.85 μM against p-ERK1/2. DPAP inhibits the expression of p-MEK1/2 and disrupts the Ras-ERK signaling pathway. DPAP inhibits the expression of COX-2 in nerve cells. DPAP damages DNA and mitochondria, induces Apoptosis via the mitochondrial pathway, and upregulates PD-L1. DPAP inhibits melanoma metastasis and angiogenesis, and inactivates spinal microglia and astrocytes. DPAP exhibits anti-melanoma activity and can be combined with anti-PD-1 monoclonal antibodies to modify anti-tumor effects. DPAP is applicable for the research of melanoma.

KRAS G12C inhibitor 53 (Compound 1) is a KRAS G12C inhibitor.

KRASG12D-IN-6 is a PROTAC target protein ligand that can be used to synthesize CH091138 (HY-175025). CH091138 is a potent and selective KRASG12D PROTAC degrader with anti-tumor activity.

KRASG12C IN-14 (compound 15) is an inhibitor targeting the KRAS G12C mutation. KRASG12C IN-14 inhibits CYPA-dependent KRAS-BRAF with an IC₅₀ of 0.002 μM. KRASG12C IN-14 inhibits ERK phosphorylation in NCI-H358 cells with an IC₅₀ of 0.002 μM.

KRAS G12C inhibitor 33 is a KRAS G12C inhibitor extracted from patent WO2021244603A1, compound 1. KRAS G12C inhibitor 33 can be used for the research of cancer.

KRASG12C IN-15 (Compound 21) is the orally active inhibitor for KRAS^G12C, and inhibits SOS1-mediated GDP/GTP exchange with an IC₅₀ of 19 nM. KRASG12C IN-15 inhibits the phosphorylation of ERK with IC₅₀ of 0.051 μM. KRASG12C IN-15 inhibits the cell viability of KRAS^G12C mutated MIA PaCa-2 with IC₅₀ of 0.023 μM. KRASG12C IN-15 exhibits antitumor effect in MIA PaCa-2 xenograft mouse models.

ZINC57632462 (ACA-6) is a non-covalent allosteric KRAS inhibitor. ZINC57632462 disrupts nucleotide exchange and inhibits RAS-effector interaction. ZINC57632462 can be used for the research of cancer.