K-Ras
K-Ras (KRAS) is a small GTPase that functions as a molecular switch within the RAS/MAPK signaling network, cycling between inactive GDP-bound and active GTP-bound states to regulate cell proliferation, differentiation, and survival[1][2]. Mechanistically, activated KRAS transduces signals from cell-surface receptors to downstream effectors, including the MAPK/ERK and PI3K/AKT pathways, thereby coordinating cellular growth and stress-response programs[1][3]. Oncogenic mutations impair GTP hydrolysis and maintain persistent KRAS signaling, resulting in sustained activation of proliferative pathways that contribute to tumor initiation, progression, and therapeutic resistance across multiple cancer types, particularly pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer[2][3][4]. In disease models, mutant KRAS also reshapes the tumor microenvironment through inflammatory and immune-regulatory signaling, further supporting tumor development and immune evasion[3][2]. Compared with the related RAS isoforms HRAS and NRAS, KRAS is the most frequently altered RAS family member in human cancer and accounts for the majority of oncogenic RAS mutations, highlighting its distinct biological and clinical importance[2][5]. For experimental applications, the development of mutation-selective inhibitors, especially KRAS^G12C^ inhibitors, has established a tractable platform for studying KRAS-dependent signaling and therapeutic resistance mechanisms, although resistance remains a major challenge for long-term clinical efficacy[2][5].
References:
- [1]. K-Ras gene information.
- [2]. Huang L, et al. KRAS mutation: from undruggable to druggable in cancer. Signal Transduct Target Ther. 2021 Nov 15;6(1):386. [Content Brief]
- [3]. Uniyal P, et al. KRAS Mutations in Cancer: Understanding Signaling Pathways to Immune Regulation and the Potential of Immunotherapy. Cancers (Basel). 2025 Feb 25;17(5):785. [Content Brief]
- [4]. Suda K, et al. Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation. Cancer Metastasis Rev. 2010 Mar;29(1):49-60. [Content Brief]
- [5]. Riedl JM, et al. Emerging landscape of KRAS inhibitors in cancer treatment. Cancer Cell. 2026 Mar 9;44(3):471-497. [Content Brief]
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K-Ras Related Products (283)
Related Products (283)
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Zecdarasib hydrochloride dihydrate
0 ImagesZecdarasib hydrochloride dihydrate is a Kirsten rat sarcoma virus oncogene homolog (KRAS) inhibitor with antitumor activity. Zecdarasib hydrochloride dihydrate can be used in tumor-related research.
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KRAS G13D-IN-1
0 ImagesCat. No.: HY-161066KRAS G13D-IN-1 (Compound 41) is a selective and covalently reversible inhibitor of KRASG13D (IC50: 0.41 nM). The selectivity for KRASG13D is 29-fold against KRAS wild type. KRAS G13D-IN-1 is an inhibitor of the GDP state and targets the SWII binding pocket of KRASG13D. KRAS G13D-IN-1 inhibits KRAS binding to GDP and turns on/off downstream signaling cascades. KRAS G13D-IN-1 can be used in the research of colon cancer.
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Spiclomazine
0 ImagesSynonyms: ClospirazineSpiclomazine (Clospirazine) is a potent mutant KRAS(G12C) inhibitor that selectively inhibits mutant KRAS-driven pancreatic cancer. Spiclomazine can eliminate KRas-GTP levels in KRAS-driven pancreatic cancer and effectively inhibit RAS-mediated signaling. Spiclomazine significantly inhibits tumor progression in mouse renal capsule xenotransplantation models.
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SHY-855
0 ImagesSHY-855 is a pan RAS inhibitor. SHY-855 effectively prevents the binding of K-Ras proteins and other members of the Ras superfamily of small GTPases with IC50 values of 0.3-5 μM. SHY-855 effectively inhibits the phosphorylation of MEK, ERK1/2, and AKT downstream of K-Ras. SHY-855 inhibits the formation of the Ras-GTP activity complex. SHY-855 can be used to the studies of pancreatic cancer and non-small cell lung cancer.
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KRAS G12D-IN-31
0 ImagesKRAS G12D-IN-31 is a potent KRAS G12D inhibitor with an IC50 of < 100 nM. KRAS G12D-IN-31 inhibits the proliferation of RAS-dependent cells (KRASG12C, KRAS G12D, KRASG12V and KRASWT). KRAS G12D-IN-31 can be used to study non-small cell lung cancer, gastric cancer, colon cancer, and malignant melanoma.
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MRTX1133 formic
0 ImagesCat. No.: HY-134813AMRTX1133 formic is a noncovalent, potent, and selective KRAS G12D inhibitor. MRTX1133 formic optimally fills the switch II pocket and extends three substituents to favorably interact with the protein, resulting in an estimated KD against KRAS G12D of 0.2 pM. MRTX1133 formic prevents SOS1-catalyzed nucleotide exchange and/or formation of the KRASG12D/GTP/RAF1 complex, thereby inhibiting mutant KRAS-dependent signal transduction. MRTX1133 formic shows efficacy in tumor models harboring KRAS G12D mutations.
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ARS-1630
0 ImagesCat. No.: HY-U00417CAS No.: 1698055-86-5ARS-1630, a less active enantiomer of ARS-1620, is a novel inhibitor of mutant K-ras G12C extracted from patent WO 2015054572 A1.
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RM-046
0 ImagesCat. No.: HY-186087CAS No.: 3058972-05-4RM-046 is an orally active, selective ternary complex inhibitor of KRASQ61H (active form). RM-046 forms a ternary complex with cyclophilin A, binds to active KRASQ61H in a non-covalent manner, blocks effector binding via steric hindrance and inhibits downstream signal transduction. RM-046 inhibits ERK phosphorylation and cancer cell proliferation, and induces sustained RAS pathway signal inhibition, anti-tumor activity and tumor regression in preclinical xenograft models. RM-046 can be used for the research of KRASQ61H mutant cancers.
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RMC-9945
0 ImagesSynonyms: RM-044RMC-9945 (RM-044) is a selective, covalent, and orally active RAS (ON) G12D inhibitor. RMC-9945 enhances the transcriptional activity of β-Catenin/TCF. RMC-9945 induces cell state transition, forcing metastatic colorectal cancer cells to switch from the Emp1+ state to the Lgr5+ stem cell-like state. RMC-9945 achieves durable disease control in preclinical models of colorectal cancer with early liver metastasis, but shows reduced activity in late-stage metastasis models. RMC-9945 can be used in research related to metastatic colorectal cancer and pancreatic ductal adenocarcinoma.
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MRTX-EX185
0 ImagesCat. No.: HY-145962CAS No.: 2621927-57-7MRTX-EX185 is a potent KRAS (G12D) inhibitor with an IC50 of 90 nM. MRTX-EX185 can binds both GDP-loaded and active GNP states of KRAS and KRAS (G12D). MRTX-EX185 exhibits broad-spectrum binding properties with IC50s of 110, 290, 130 and 240 nM for KRAS WT, KRAS (G12C), KRAS (Q61H), KRAS (G13D). MRTX-EX185 also binds GDP-loaded HRAS. MRTX-EX185 can be used to study various RAS-driven tumors (such as pancreatic cancer) .
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KRAS G12C inhibitor 15
0 ImagesKRAS G12C inhibitor 15 is a potent KRAS G12C inhibitor extracted from patent WO2019110751A1, compound 22, has an IC50 of 5 nM.
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KRAS G12C inhibitor 28
0 ImagesKRAS G12C inhibitor 28 is a KRAS G12C inhibitor with an IC50 of 57 nM. KRAS G12C inhibitor 28 has antitumor effects (WO2021113595A1; Example 1).
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KRAS G12C inhibitor 14
0 ImagesKRas G12C inhibitor 14 (Compound 17) is a potent KRAS G12C inhibitor (IC50 = 18 nM).
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SHY-867
0 ImagesSHY-867 is a pan RAS inhibitor. SHY-867 effectively prevents the binding of K-Ras proteins and other members of the Ras superfamily of small GTPases with EC50 values of 0.5-3 μM. SHY-867 effectively inhibits the phosphorylation of MEK, ERK1/2, and AKT downstream of K-Ras. SHY-867 inhibits the formation of the Ras-GTP activity complex. SHY-867 can be used to the studies of pancreatic cancer and non-small cell lung cancer.
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BI-0474
0 ImagesBI-0474 is a potent KRASG12C 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.
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KRas G12C inhibitor 1
0 ImagesCat. No.: HY-112491CAS No.: 2158297-28-8KRas G12C inhibitor 1 is a compound that inhibits KRas G12C, extracted from patent US 20180072723 A1.
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Kras4B G12D-IN-1
0 ImagesKras4B G12D-IN-1 is a Kras4B G12D inhibitor with anticancer effects. Kras4B G12D-IN-1 decreases Kras protein expression in mouse embryonic fibroblasts (MEF) expressing Kras4B G12D (WO2016179558A1, Comp 994566).
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PROTAC pan-KRAS degrader-1
0 ImagesCat. No.: HY-176489CAS No.: 3043908-63-7PROTAC pan-KRAS degrader-1 is a pan-KRAS-targeting PROTAC degrader for degrading different KRAS mutation types, such as G12D, G12C, G12V, and G13D. PROTAC pan-KRAS degrader-1 potently degrades KRAS mutation (G12D) in AGS cells, with a DC50 of 1.1 nM, Dmax of 95%. PROTAC pan-KRAS degrader-1 can be used to search diseases caused by KRAS mutation or amplification, especially cancers such as breast cancer, bladder cancer, gastric cancer, etc.
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(4R)-BBO-8520
0 ImagesCat. No.: HY-158107ACAS No.: 2893809-52-2(4R)-BBO-8520 (Compound 314), an isomer of BBO-8520 (HY-158107), is a selective KRAS G12C inhibitor. BBO-8520 has the characteristics of KRAS G12C (OFF) inhibitor and the function of blocking KRAS G12C (ON) signal. BBO-8520 inhibits cell proliferation by inhibiting KRASG12C (ON) by binding GTP protein. BBO-8520 can block RAS-RAF1 interaction and return KRAS G12C to the inactive (OFF) state. (4R)-BBO-8520 can be used for the research of cancer.
