Ras Degrader

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)).

MCB-36 is a VHL-recruiting pan-KRAS PROTAC degrader without affecting KRAS transcription. MCB-36 exhibits minimal effects on HRAS and NRAS protein levels. MCB-36 binds to the GDP-loaded state of G12D, G12C, G12V, and wild-type KRAS with high affinities K_d ≈ 1 pM). MCB-36 decreases p-ERK levels, leading to cell apoptosis. MCB-36 effectively suppress KRAS^G12C inhibitor-resistant cancer cells and remodel the tumor immune microenvironment. MCB-36 can be used for the study of colorectal cancer and lung cancer (Pink: Target protein ligand; Blue: E3 ligand (HY-112078); Black: Linker (HY-W091879)).

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 KRASG12C proteolysis targeting chimera (PROTAC). YN14 is highly potent and selective KRASG12C degrader and induces a stable KRASG12C: YN14: VHL ternary complex with low binding free energy (ΔG). YN14 has antiproliferative effects and significantly inhibits KRASG12C-mutant cancer cell growth. YN14 leads to tumor regression with tumor growth inhibition (TGI%) rates more than 100 % in the MIA PaCa-2 xenograft model.

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 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 effective and selective PROTAC degrader targeting KRAS^G12D (DC₅₀ = 79.5 nM in AsPC-1 cells). ZJK-807 shows minimal impact on wild-type KRAS or other mutants (G12C/S/V, G13D), inducing mutant-specific cytotoxicity. 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. Yellow: KRAS^G12D ligand (HY-W087383); Green: E3 ligase CRBN ligand (HY-178507); Black: Linker (HY-178506).

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.

KRAS degrader-1 is a potent KRAS degrader. KRAS degrader-1 targets specific proteins for degradation via the autophagy-lysosomal degradation pathway. KRAS degrader-1 is suitable for use in cancer research. (Blue: KRAS G12C-IN-72 (HY-128414); Black: Linker (HY-175587); Pink: 5-Iodoindolin-2-one (HY-76986); Blue + Black: KRAS ligand-Linker Conjugate 7 (HY-175586)).