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Ras Inhibitors

Ras is a G protein, or a guanosine-nucleotide-binding protein. Ras is involved in the control of intracellular signaling networks, such as cell proliferation, differentiation, adhesion, apoptosis, and migration. Ras and ras-related proteins are often deregulated in cancers, leading to decreased apoptosis.  [show the full text]

Other Apoptosis Related Inhibitors

Caspase Bcl-2 p53 Ferroptosis PD-1/PD-L1 Survivin TNF-alpha MDM2/MDMX KRas IAP

Isoform-selective Products

Cat.No. Product Name Information Product Use Citations Product Validations
E5848New ERAS-0015 ERAS-0015(JYP0015) is a tricomplex inhibitor of panRAS(ON) targeting of active RAS, it binds to Cyclophilin A (CYPA) to form a high-affinity complex that sterically occludes RAS–effector interactions. It exhibits potential for research in RAS-mutant solid tumors.
E6403New RMC5127 RMC-5127 is an orally bioavailable, mutant-selective tri-complex inhibitor of the GTP-bound (ON) form of RASG12V. It non-covalently binds cyclophilin A (CypA) to form a binary complex that creates a high-affinity tri-complex with RASG12V(ON), sterically blocking effector binding and potently suppressing RAS signaling. It exhibits CNS penetration and induces robust anti-tumor activity in KRASG12V-mutant NSCLC, PDAC, and CRC xenograft models.
E1858 RMC-7977 RMC-7977 is a potent, reversible, tri-complex oral inhibitor that selectively targets active (GTP-bound) forms of KRAS, HRAS, and NRAS, which exhibits broad-spectrum activity against both mutant and wild-type variants (a RASMULTI (ON) inhibitor). It also exhibits significant anti-tumor efficacy in pancreatic ductal adenocarcinoma (PDAC).
Cellular Oncology, 2025, 1317-1335
Cell Oncol (Dordr), 2025, 10.1007/s13402-025-01075-4
E1597 Daraxonrasib (RMC-6236) Daraxonrasib (RMC-6236) is a RAS(ON) multi-selective noncovalent inhibitor of the active, GTP-bound state of both mutant and wild-type variants of canonical RAS isoforms with broad therapeutic potential. RMC-6236 exhibits strong anticancer efficacy in RAS-addicted cell lines, especially those with mutations at codon 12 of KRAS.
Cell Oncol (Dordr), 2025, 10.1007/s13402-025-01075-4
bioRxiv, 2025, 2025.07.07.663486
E1051 MRTX1133 MRTX1133 is a highly selective inhibitor of mutant KRAS G12D and can reversibly binds to the activated and inactivated KRAS G12D mutants and inhibit their activity. The specificity of MRTX1133 to KRAS G12D is more than 1000 times that of wild-type KRAS.
J Exp Clin Cancer Res, 2025, 44(1):164
Cell Rep, 2025, 44(6):115774
Br J Cancer, 2025, 10.1038/s41416-025-03162-7
E1962 Zoldonrasib (RMC-9805) Zoldonrasib (RMC-9805) is an orally active inhibitor of KRAS G12D that inhibits RAS signaling, leading to apoptosis in cancer cells with the KRAS G12D mutation.
S8830 AMG 510 (Sotorasib) Sotorasib (AMG510) is a potent KRAS G12C covalent inhibitor with potential antineoplastic activity.This AMG510 is a chiral compound.
Cell Res, 2025, 10.1038/s41422-025-01085-9
Cancer Res, 2025, 10.1158/0008-5472.CAN-25-0450
Cell Death Dis, 2025, 16(1):661
S8959 BI-2852 BI-2852 is a potent inhibitor of KRAS that binds with nanomolar affinity to a pocket between switch I and II on RAS. This compound blocks all GEF, GAP, and effector interactions with KRAS, leading to inhibition of downstream signaling and an antiproliferative effect in the low micromolar range in KRAS mutant cells.
Eur J Cell Biol, 2023, 102(2):151314
S8884 Adagrasib (MRTX849) Adagrasib (MRTX849) is a potent, selective, and covalent KRASG12C inhibitor that exhibits favorable drug-like properties. It selectively modifies mutant cysteine 12 in GDP-bound KRASG12C and inhibits KRAS-dependent signaling.
Br J Cancer, 2025, 10.1038/s41416-025-03162-7
iScience, 2025, 28(9):113374
Mol Cancer Ther, 2025, 10.1158/1535-7163.MCT-25-0022
E4651 HRS-4642 HRS-4642 is a selective inhibitor of KRAS G12D with a Kd value of 0.083 nM. It exhibits robust anti-cancer activity against KRAS G12D-mutant cancers both in vitro and in vivo.
Journal of Experimental & Clinical Cancer Research, 2025, 68
J Exp Clin Cancer Res, 2025, 44(1):68

The RAS superfamily consists of five subfamilies – Ras, Rho, Rab, Arf, and Ran – that contain approximately 150 proteins. Abberant RAS genes are common in a wide number of human cancers. As one of the first human oncogenes identified, point mutations or aberrant transcription of RAS genes is estimated to result in 15-30% of all cancers. From these, it is known that there are three major downstream effector families: Raf, PI3K, and RalGEF.

The Ras-Raf signaling activity is critical to the Ras/MAPK signaling pathway. The Raf protein family is made up of serine/threonine kinases (A-Raf, B-Raf, and C-Raf/Raf-1) that are activated by the binding to GTP-bound Ras. The resultant effect is that the MAPK cascade signaling pathway becomes activated, leading to MEK and ERK phosphorylation that results in the activation of various transcription factors and cell cycle regulatory proteins. For tumors, constitutive activation of RAS leads to cell proliferation and survival.

RAS also shows selectivity for Class I PI3K isoforms. More specifically, while H-RAS, K-RAS, N-RAS, R-RAS, TC21, and M-RAS can activate p110α and p110γ; meanwhile, R-RAS and TC21 only activate the p110δ isoform. It has been suggested that because RAS shows specificity for p110 isoforms, there may be unique consequences of RAS activation in different cell types. As a consequence, strategies to target RAS in oncology will need to consider isoform-specific inhibitors to inhibit PI3K activity where oncogenic RAS mutations are implicated.

Tumors consisting of RAS mutations are capable of exploiting both MAPK and PI3K pathways to result in mitosis, apoptosis, motility, proliferation, and differentiation. Aside from MAPK and PI3K, RAS also interacts with a range of other proteins (p120-GAP, NF1-GAP, MEKK1, AF-6, Nore-1, Rin-1 and Canoe), however, their role in tumor activity is unclear.[1] Interestingly, of all the subfamily proteins only three constituents have been found to be mutated in a number of human cancers (K-RAS, N-RAS, and H-RAS). K-RAS mutations are the most frequently mutated of the three RAS-members, and is implicated especially in pancreatic adenocarcinomas, colorectal tumorigenesis, and lung cancer. In contrast, H-RAS mutations have been shown to be associated in 10-24% of prostate cancer cases (rate varies by demographics), small intestinal tumors, esophageal tumorigensis, and uterine carcinogenesis.[2]