Ras Degrader

MCB-36 is a pan-KRAS PROTAC degrader that recruits VHL, with a K_d value of approximately 1 pM against KRAS, and it does not affect KRAS transcription. MCB-36 continuously degrades various KRAS mutants, inhibits oncogenic KRAS signaling pathways, reduces p-ERK levels, and induces apoptosis, thereby suppressing the growth of KRAS-dependent cancer cells. In vivo, MCB-36 inhibits tumor growth, overcomes resistance to KRAS G12C inhibitors, remodels the tumor immune microenvironment and enhances immune cell infiltration. MCB-36 can be used in research related to colorectal cancer and lung cancer.

ACBI3 (compound 7), a chemical probe, is a PROTAC targeting KRAS. ACBI3 achieves in vivo degradation of oncogenic KRAS, resulting in durable pathway modulation and tumor regressions in KRAS mutant xenograft mouse models.

PROTAC K-Ras Degrader-4 (Compound 4) is a PROTAC degrader for KRAS that degrades KRAS^G12D in GP5d and degrades KRAS^G12V in cell SW620 with DC₅₀s of 1 nM and 13 nM. PROTAC K-Ras Degrader-4 inhibits MAPK signaling pathway.

PROTAC KRAS G12D degrader 1 is a selective PROTAC KRAS^G12D degrader. PROTAC KRAS G12D degrader 1 inhibits proliferation of KRAS^G12D-mutant cells and suppresses ERK phosphorylation. PROTAC KRAS G12D degrader 1 inhibits tumor growth in mice bearing AsPC-1 xenografts. PROTAC KRAS G12D degrader 1 can be used for the study of KRAS^G12D-driven cancers.(Pink: KRAS ligand (HY-175892), Blue: VHL Ligand (HY-112078), Black: Linker, E3 ligase ligand-linker conjugate (HY-175893)).

PROTAC K-Ras Degrader-1 is a K-Ras PROTAC degrader. It binds to both K-Ras and the Cereblon E3 ubiquitin ligase, bringing K-Ras into proximity with the ligase, thereby achieving its degradation and inhibition. PROTAC K-Ras Degrader-1 can be used for research in various cancers.

RP03707 is a PROTAC degrader of KRAS^G12D. RP03707 forms a ternary complex with KRAS^G12D and the CRBN E3 ligase, promoting the ubiquitination and proteasomal degradation of KRAS^G12D. RP03707 inhibits the growth of KRAS^G12D-positive tumor cells.

PROTAC KRAS G12C degrader-1 is a Cereblon-based KRAS^G12C PROTAC degrader. PROTAC KRAS G12C degrader-1 induces CRBN/ KRAS^G12C dimerization and degrades GFP- KRAS^G12C in reporter cells.

PROTAC K-Ras Degrader-3 (compound 40) is a PROTAC degrader of K-Ras with a DC₅₀ of ≤ 1 nM against SW620 KRAS G12D, and a GI₅₀ of ≤ 10 nM against SW620 3D cell growth. PROTAC K-Ras Degrader-3 can be utilized in cancer research, such as non-small-cell lung cancer (NSCLC).

pan-KRAS-IN-18 is a panKRAS inhibitor that inhibits KRAS WT and KRAS G12V with IC₅₀s of 29 and 9 nM, respectively. pan-KRAS-IN-18 exhibits antiproliferative activity in KRAS-mutant cell lines. pan-KRAS-IN-18 can be used for lung cancer research.

ACBI-4 is a selective GTP-loaded active state of KRAS (KRAS(on)) PROTAC degrader, with K_d values of 141 nM against KRAS^G12R. ACBI-4 forms a stable ternary complex with VHL, triggering ubiquitination and KRAS degradation via the ubiquitin-proteasome system. ACBI-4 induces antiproliferative effects in KRAS mutant-driven cancer cells. ACBI-4 can be used for the research of KRAS mutant-driven cancer.

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.

IPS-06061 is an orally active molecular glue forming a ternary complex of CRBN-KRAS^G12D-IPS06061, degrading KRAS^G12D with a DC₅₀ value lower than 500 nM. IPS-06061 shows a strong anti-tumor efficacy.

YN14 is a KRAS^G12C PROTAC degrader that recruits E3 ubiquitin ligase to induce the polyubiquitination and proteasomal degradation of KRAS^G12C. YN14 induces tumor cell apoptosis, cell cycle arrest, and cell migration inhibition. YN14 exhibits in vivo antitumor proliferative activity in tumor cell xenograft nude mice. YN14 can be used in cancer-related research.

PROTAC K-Ras degrader-2 (compound 48) is a KRAS G12V PROTAC degrader with an IC₅₀ of 20-200 nM for KRAS G12V/RAF1. PROTAC K-Ras degrader-2 degrades SW620 KRAS G12V with a DC₅₀ of 1-10 nM. PROTAC K-Ras degrader-2 inhibits cell growth of SW620 3D cell with an IC₅₀ of ≤10 nM. PROTAC K-Ras degrader-2 can be used for the study of colorectal cancer (CRC).

PROTAC KRAS G12C (Compound 432) degrader-2 is a PROTAC degrader that targets KRAS^G12C by recruiting cereblon. PROTAC KRAS G12C degrader-2 covalently modifies KRAS^G12C. PROTAC KRAS G12C degrader-2 can be used for the research of non-small cell lung cancer.

PROTAC 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, D_max 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.

K-Ras ligand-Linker Conjugate 8 is a Target Protein Ligand-Linker Conjugate that incorporates a ligand for KRAS (HY-162960) and a PROTAC linker, which recruits E3 ligases. K-Ras ligand-Linker Conjugate 8 can be used for synthesis of PROTAC KRAS(on) degrader ACBI-4 (HY-176792).

ZJK-807 is a highly efficient and selective KRAS^G12D PROTAC degrader (DC₅₀ = 79.5 nM in AsPC-1 cells). ZJK-807 promotes KRAS^G12D ubiquitination and degradation. ZJK-807 suppresses RAS/MAPK signaling and uniquely modulates TNF signaling and eukaryotic ribosome biogenesis. ZJK-807 can be used for the study of KRAS-driven pancreatic cancer.

MS243 is a potent KRAS^G12D PROTAC degrader with a DC₅₀ of 4.2 nM. MS243 promotes the proximity between KRAS^G12D and the VHL E3 ubiquitin ligase, drives the ubiquitination and proteasomal degradation of KRAS^G12D, and inhibits the proliferation of cancer cells harboring KRAS^G12D. MS243 can be used in the research of KRAS^G12D-carrying cancers, such as colon cancer and pancreatic cancer.

KRAS inhibitor-22 (compound FB9/6B9) is a potent inhibitor of K-Ras. KRAS inhibitor-22 targets to Kras 4B(G12D) and (G12C), which can be used for cancer research.