SWI/SNF Complex Degrader

LO-3-62 is a SMARCA2/4 degrader. LO-3-62 incorporates a truncated fumaramide linker and conjugates it to a SMARCA2/4 inhibitor. LO-3-62 binds covalently to the CUL4^DCAF16 E3 ubiquitin ligase, inducing proteasome-dependent degradation of SMARCA2/4. LO-3-62 can be used in studies of monocytic leukemia.

JP-2-249 is a molecular glue that acts as a potent degrader of SMARCA2. JP-2-249 shows decreasing protein level of SMARCA2 in MV-4-11 cells at 1-10 μM.

PROTAC SMARCA2 degrader-18 (Example144) is a PROTAC SMARCA2 degrader. PROTAC SMARCA2 degrader-18 has the potential for the research of non-small cell lung cancer (NSCLC).

PROTAC SMARCA2/4 degrader-43 is a PROTAC degrader targeting SMARCA2/4, which induces ubiquitination and proteasomal degradation of the protein. PROTAC SMARCA2/4 degrader-43 is applicable to cancer-related research.

PROTAC SMARCA2/4-degrader-20 (Compound I-405) is a PROTAC degrader for catalytic subunit of the SWI/SNF complex SMARCA2. PROTAC SMARCA2/4-degrader-20 degrades SMARCA2 in A549 and MV411 with DC₅₀ <100 nM, degrades SMARCA4 in MV411 with DC₅₀ of 100-500 nM

PROTAC SMARCA2 degrader-34 (compound 52) is a selective SMARCA2 PROTAC degrader (DC50 in HeLa cell: < 0.1 μM for SMARCA2, > 1 μM for SMARCA4). PROTAC SMARCA2 degrader-34 can be used for study of cancer. (Pink: SMARCA2 ligand (HY-178414) ; Blue: E3 ligand (HY-168055) ; Black: linker).

PROTAC SMARCA2/4-degrader-15 (Compound I-335) is a PROTAC degrader for catalytic subunit of the SWI/SNF complex SMARCA2 and SMARCA4. PROTAC SMARCA2/4-degrader-15 degrades SMARCA2 in A549 with DC₅₀ <100 nM, degrades SMARCA4 in MV411 with DC₅₀ <100 nM

PROTAC SMARCA2/4 degrader-9 is a SMARCA2 and SMARCA4 PROTAC degrader. PROTAC SMARCA2/4 degrader-9 induces protein ubiquitination and subsequent proteasome-mediated degradation. PROTAC SMARCA2/4 degrader-9 can be used in cancer-related research.

PROTAC SMARCA2 degrader-23 (Example 1) is a potent and selective PROTAC SMARCA2 degrader, with a DC₅₀ of <100 nM. PROTAC SMARCA2 degrader-23 has the potential for the research of cancer.

PROTAC SMARCA2/4 degrader-41 is a SMARCA2/4 PROTAC degrader with a DC₅₀ and IC₅₀ both < 0.1 μM. PROTAC SMARCA2/4 degrader-41 is applicable to research on SMARCA2/4-related or SMARCA2/4-deficient cancers.

PROTAC SMARCA2 degrader-32 is a potent, selective SMARCA2 PROTAC degrader, with DC₅₀ values of 1.3 nM and 94 nM against SMARCA2 and SMARCA4, respectively. PROTAC SMARCA2 degrader-32 exhibits IC₅₀ against SMARCA2, SMARCA4 and the VHL E3 ubiquitin ligase of 30 nM, 63 nM and 25 nM, respectively. PROTAC SMARCA2 degrader-32 inhibits the growth of SMARCA4-deficient cancer cells. It can be used in research on cancers such as fibrosarcoma.

PROTAC SMARCA2/4 degrader-7 is a PROTAC-based degrader that targets SMARCA2 and SMARCA4, with DC₅₀ values both < 100 nM. PROTAC SMARCA2/4 degrader-7 can be used in cancer-related research.

PROTAC SMARCA2/4 degrader-28 is a heterobifunctional PROTAC degrader targeting SMARCA2 and SMARCA4. PROTAC SMARCA2/4 degrader-28 forms a ternary complex with CRL2_VHL E3 ligase and SMARCA2 or SMARCA4, mediating the ubiquitination and degradation of SMARCA2, while acting as a partial degrader of SMARCA4. PROTAC SMARCA2/4-degrader-28 can be used in cancer-related research.

PROTAC BRM/BRG1 degrader-1 (Example 253) is a PROTAC BRM/BRG1 degrader, with DC₅₀ of 10-100 nM for BRM, > 1 μM for BRG1. PROTAC BRM/BRG1 degrader-1 can be used for cancer research.

PROTAC BRM degrader-1 is a VHL-recruiting PROTAC degrader that exhibits higher selectivity for the degradation of SMARCA2 (BRM) over its highly homologous protein SMARCA4 (BRG1). The K_D values of PROTAC BRM degrader-1 for BRM and BRG1 are 72 nM and 108 nM, respectively. PROTAC BRM degrader-1 can be used in studies related to selective SMARCA2 degradation, SWI/SNF function, and SMARCA4-mutant non-small cell lung cancer.

PROTAC SMARCA2/4 degrader-11 is a PROTAC degrader targeting SMARCA2 and SMARCA4. PROTAC SMARCA2/4 degrader-11 induces protein ubiquitination and subsequent proteasome-mediated degradation. PROTAC SMARCA2/4-degrader-11 can be used in cancer-related research.

PROTAC SMARCA2/4-degrader-4 (Compound I-434) is a PROTAC degrader for catalytic subunit of the SWI/SNF complex SMARCA2 and SMARCA4. PROTAC SMARCA2/4-degrader-4 degrades SMARCA2 in MV411 and in A549 with DC₅₀ <100 nM, degrades SMARCA4 in MV411 with DC₅₀ <100 nM. (Pink: Ligand for target protein (HY-159472); Black: Linker (HY-159478); Blue: Ligand for E3 ligase (S,R,S)-AHPC (HY-125845))

PROTAC SMARCA2/4 degrader-44 is a PROTAC-based protein degrader targeting SMARCA2/4, which induces ubiquitination and subsequent degradation of the target proteins. PROTAC SMARCA2/4 degrader-44 is applicable for cancer-related research.

PROTAC SMARCA2 degrader-24 (Compound 34) is a PROTAC degrader for SMARCA2 with a DC₅₀ < 0.1 µM in HeLa. PROTAC SMARCA2 degrader-24 degrades SMARCA4 with a DC₅₀ > 10 μM in HeLa.

PROTAC SMARCA2/4 degrader-27 is a VHL-recruiting PROTAC degrader targeting SMARCA2 and SMARCA4, derived from structure-guided modification of PROTAC SMARCA2/4 degrader-28 (HY-162835). PROTAC SMARCA2/4-degrader-27 forms a cooperative ternary complex with CRL2_VHL E3 ligase to induce ubiquitination and degradation. PROTAC SMARCA2/4-degrader-27 induces a novel protein-protein interaction between VHL and SMARCA2/SMARCA4, thereby stabilizing ternary complex formation and promoting proteasomal degradation of target proteins. PROTAC SMARCA2/4-degrader-27 exhibits enhanced cell permeability and stronger ternary complex formation ability, leading to improved degradation activity. PROTAC SMARCA2/4-degrader-27 can be used in cancer-related research^[1].