K-Ras Degrader

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)).

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.

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.

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 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).

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 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)).

YF135 is a KRAS^G12C PROTAC degrader that mediates proteasomal degradation of KRAS^G12C in a reversible manner. In KRAS^G12C-mutant H358 and H23 lung cancer cells, the DC₅₀ values of YF135 for KRAS degradation are 3.61 μM and 4.53 μM, respectively. YF135 attenuates the pERK signaling pathway in cancer cells. YF135 is applicable for lung cancer-related research.

KRAS ligand 5 is the target protein ligand for PROTAC K-Ras Degrader-3 (HY-168054). PROTAC K-Ras Degrader-3 can specifically degrade KRAS mutated proteins.

CH091138 is a potent and selective KRASG12D PROTAC degrader with DC₅₀s of 148.3 nM in HeLa cells and 469.8 nM in AsPC-1 cells. CH091138 selectively degrades exogenous and endogenous KRASG12D but not KRAS^WT or other KRAS mutants (G12C/G12S/G12V), depending on the VHL-mediated ubiquitin-proteasome system. CH091138 exhibits potent anti-tumor activity and induces cancer cell apoptosis. CH091138 can be used for the studies of pancreatic cancer and colon cancer. (Pink: KRASG12D ligand (HY-175144); Blue: VHL E3 ligase ligand (HY-138678); Black: Linker; VHL E3 ligase ligand + Linker (HY-136006B)).

(R)-ACBI-4 is an isomer of ACBI-4 (HY-176792). ACBI-4 is a selective GTP-loaded active state of KRAS (KRAS(on)) PROTAC degrader. ACBI-4 has significant anti-proliferative effect and potently degrades multiple KRAS mutants in cancer cells, such as KRASG12R.

KRAS G12D ligand-3 is a KRAS G12D PROTAC ligand. KRAS G12D ligand-3 can be conjugated with E3 ligase Ligand (HY-170348) and linke (HY-W895436) to synthesize KRAS G12D PROTAC degrader MS243 (HY-181728). MS243 can be used for cancer research.