SWI/SNF Complex Degrader

AU-15330 is a proteolysis-targeting chimera (PROTAC) degrader of the SWI/SNF ATPase subunits, SMARCA2 and SMARCA4. AU-15330 induces potent inhibition of tumour growth in xenograft models of prostate cancer and synergizes with the AR antagonist enzalutamide. AU-15330 induces disease remission in castration-resistant prostate cancer (CRPC) models without toxicity.

ACBI1 is a potent and cooperative SMARCA2, SMARCA4 and PBRM1 degrader with DC₅₀s of 6, 11 and 32 nM, respectively. ACBI1 is a PROTAC degrader. ACBI1 shows anti-proliferative activity. ACBI1 induces apoptosis.

AU-24118 is a selective and orally bioavailable PROTAC degrader of mSWI-SNF ATPases (SMARCA2 and SMARCA4) and PBRM1. AU-24118 integrates a bait moiety binding to the bromodomains of SMARCA2 and SMARCA4, along with a ligand moiety for CRBN ligase. AU-24118 demonstrates tumor regression in prostate cancer model. AU-24118 can be studied to combat prostate cancer. (Pink: PBRM1/SMARCA2,4 ligand (HY-171774); Blue: CRBN ligand (HY-171775)).

YD23 is a selective SMARCA2 PROTAC degrader with DC₅₀ values of 64 nM and 297 nM in H1792 cells and H1975 cells. YD23 induces degradation of SMARCA2, which is synthetic lethal to SMARCA4. YD23 reduces chromatin accessibility only in SMARCA4 deficient cells, including cell cycle and cell growth regulatory genes. YD23 selectively inhibits growth of SMARCA4 mutant lung cancer cells. YD23 has potent tumor growth inhibitory activity in SMARCA4-mutant xenografts. YD23 can be used for the study of non-small cell lung cancer (NSCLC).

SMD-3040 is a potent and selective SMARCA2 PROTAC degrader (DC₅₀: 12 nM; D_max: 91%). SMD-3040 can inhibit tumor cell proliferation and exhibits antitumor activity. SMD-3040 can be used in the study of tumors such as melanoma.

PRT3789 is a selective SMARCA2 PROTAC degrader (DC₅₀ in HeLa cell: 0.72 nM for SMARCA2, 14 nM for SMARCA4). PRT3789 forms a stable ternary complex with Von Hippel-Lindau (VHL) E3 ligase, induces polyubiquitination at SMARCA2-specific lysine residues, and drives proteasome-dependent SMARCA2 degradation. PRT3789 disrupts SWI/SNF chromatin remodeling complex integrity, induces dissociation of specific subunits, suppresses oncogenic gene expression, reduces chromatin accessibility, and upregulates antigen processing/presentation-related gene expression. PRT3789 induces synthetic lethality, inhibits proliferation and colony formation, and drives tumor growth inhibition and regression in SMARCA4-deficient contexts. PRT3789 can be used for the research of SMARCA4-mutated solid tumors, non-small cell lung cancer, endometrial cancer, colorectal cancer, bladder cancer, esophageal cancer, ovarian cancer, and gastric cancer.

SMD-3040 formate is a potent and selective SMARCA2 PROTAC degrader (DC₅₀: 12 nM; D_max: 91%). SMD-3040 formate can inhibit tumor cell proliferation and exhibits antitumor activity. SMD-3040 formate can be used in the study of tumors such as melanoma.

G-6599 is a monovalent molecular glue-like degrader of SMARCA2/SMARCA4. G-6599 covalently binds to a specific cysteine residue of the E3 ligase FBXO22 in a biotransformation-independent manner, promotes the formation of a ternary complex with SMARCA2/A4, and achieves efficient and specific degradation of the two proteins via the ubiquitin-proteasome pathway. G-6599 is applicable to the research of androgen-dependent prostate cancer and mutant non-small cell lung cancer.

PROTAC SMARCA2/4 degrader-38 is a degrader SMARCA2/4 PROTAC (DC₅₀: 3.0 nM and 4.0 nM respectively). PROTAC SMARCA2/4 degrader-38 promotes the ubiquitination and degradation of SMARCA2/4. PROTAC SMARCA2/4 degrader-38 blocks the G0/G1 cell cycle and induces apoptosis. PROTAC SMARCA2/4 degrader-38 can be used in acute myeloid leukemia (AML) research.

YDR1 is a potent PROTAC SMARCA2 degrader, with the DC₅₀ of 7.7 nM. YDR1 plays an important role in SMARCA4 mutant cancers(Sturcture Note:(Blue: Cereblon ligand (HY-W087383), Black: linker；Pink: SMARCA2 ligand (HY-44012B)).

SMD-3040 TFA is a potent and selective SMARCA2 PROTAC degrader (DC₅₀: 12 nM; D_max: 91%). SMD-3040 TFA can inhibit tumor cell proliferation and exhibits antitumor activity. SMD-3040 TFA can be used in the study of tumors such as melanoma. (SMARCA2/4-ligand (HY-171765); HY-112078 VHL ligand (HY-112078))

SMD-3236 is a SMARCA2 PROTAC degrader with a DC₅₀ of 0.5 nM, a D_max of 98%, and an IC₅₀ of 42.2 nM against human SMARCA2. SMD-3236 induces proteasome- and ubiquitin-like modification-dependent degradation of SMARCA2 protein by binding to SMARCA2 and VHL-1. SMD-3236 inhibits the growth of SMARCA4-deficient cancer cells. SMD-3236 induces significant and persistent depletion of SMARCA2 in tumor tissues. SMD-3236 suppresses tumor growth in SMARCA4-deficient human cancer xenograft models. SMD-3236 can be used in research related to SMARCA4-deficient cancers such as melanoma, non-small cell lung cancer, and acute myeloid leukemia.

PROTAC SMARCA2/4-degrader-18 (Compound I-348) is a PROTAC degrader for catalytic subunit of the SWI/SNF complex SMARCA2 and SMARCA4. PROTAC SMARCA2/4-degrader-18 degrades SMARCA2 in A549 with DC₅₀ <100 nM, degrades SMARCA4 in MV411 with DC₅₀ <100 nM.

PROTAC SMARCA2/4-degrader-10 (compound I-399) is a potent SMARCA2 degrader with an DC₅₀ value of ＜100 nM. PROTAC SMARCA2/4-degrader-10 has the potential for the research of cancer.

SMARCA2/4 degrader-1 is a SMARCA2/4 molecular glue degrader with a DCAF16 EC₅₀ of 110 nM. SMARCA2/4 degrader-1 covalently adducts at cysteine to form a ternary complex with SMARCA2/4 and recruits CUL4^DCAF16 and CRL1^FBXO22 E3 ligase complexes. SMARCA2/4 degrader-1 induces ubiquitination and proteasomal degradation of SMARCA2/4. SMARCA2/4 degrader-1 can be used for research of SMARCA4-deficient malignancies, non-small cell lung cancer (NSCLC), and colorectal cancer.

PROTAC SMARCA2 degrader-21 (Compound I-5) is a PROTAC degrader for SMARCA, that degrades SMARCA2 with a DC₅₀ of 10-50 nM in A549 cell, and degrades SMARCA2 and SMARCA4 in MV411 with DC₅₀ of <1 nM and >100 nM, respectively.

PROTAC SMARCA2/4-degrader-6 (compound I-438) is a SMARCA2/4 degrader. PROTAC SMARCA2/4-degrader-6 has the potential for the research of cancer.

(S,R,S)-AHPC-Me-amide-C9-acid is a E3 ligase ligand-linker conjugate, used for the synthesis of PROTAC SMARCA2 degrader-31 (HY-168234).

PROTAC SMARCA2 degrader-36 (Compound 26) is a selective and potent SMARCA2 PROTAC degrader with a DC₅₀ of 51 nM. PROTAC SMARCA2 degrader-36 promotes ubiquitination and degradation of SMARCA2. PROTAC SMARCA2 degrader-36 exhibits anticancer activity against non-small cell lung cancer. PROTAC SMARCA2 degrader-36 can be used in studies related to SMARCA4-deficient cancers.

PROTAC SMARCA2/4 degrader-36 (Compound 29) is an effective dual degrader of SMARCA2/4,with DC₅₀ values of 0.22 nM and 0.85 nM for SMARCA2 and SMARCA4, respectively. PROTAC SMARCA2/4 degrader-36 has anti-cell proliferation activity.