SMARCA2

BRM, BAF190B, SNF2L2

SMARCA2 (also known as BRM) encodes one of the two mutually exclusive ATPase catalytic subunits of the mammalian SWI/SNF (BAF) chromatin-remodeling complex and regulates transcription through ATP-dependent modulation of chromatin accessibility and nucleosome positioning^[1]^[2]. Mechanistically, SMARCA2 provides the enzymatic activity required for chromatin remodeling, thereby influencing gene-expression programs linked to cellular differentiation, proliferation, and lineage-specific transcriptional control^[1]^[3]. Within the BAF complex, SMARCA2 functions in a paralogous relationship with SMARCA4 (BRG1), and either ATPase can support remodeling activity; however, the two proteins are incorporated in mutually exclusive complexes and can regulate distinct transcriptional programs despite substantial functional overlap^[2]^[4]. This distinction has important disease implications because loss of SMARCA4 frequently creates a dependency on residual SMARCA2 activity, establishing a synthetic-lethal relationship that has been validated in multiple cancer models^[4]^[5]^[6]. In developmental disease, recurrent SMARCA2 mutations are associated with Nicolaides-Baraitser syndrome, highlighting a nonredundant role in human development and enhancer regulation^[3]^[7]. For experimental applications, increasing attention has focused on pharmacologic inhibition or targeted degradation of SMARCA2, particularly in SMARCA4-deficient tumors, where selective suppression of SMARCA2 produces antitumor effects and provides a tractable strategy for studying SWI/SNF ATPase dependence^[5]^[6]^[8]. Studies further indicate that the ATPase domain represents a more effective therapeutic target than bromodomain inhibition alone in SWI/SNF-mutant cancer settings^[6].

References:

[1]. Cantley J, et al. Selective PROTAC-mediated degradation of SMARCA2 is efficacious in SMARCA4 mutant cancers. Nat Commun. 2022 Nov 10;13(1):6814. [Content Brief]

[2]. Vangamudi B, et al. The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNF-Mutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies. Cancer Res. 2015 Sep 15;75(18):3865-3878. [Content Brief]

[3]. Kofink C, et al. A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo. Nat Commun. 2022 Oct 10;13(1):5969. [Content Brief]

SMARCA2 Related Products (18):

By Type:	Pan (9) Selective (5)
By Effects:	Inhibitors (3) Degraders (8) Ligands (7)

Cat. No.	Product Name	Effect	Purity

HY-145388

AU-15330	Degrader	99.89%
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.

HY-128359

ACBI1	Degrader	99.92%
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.

HY-159607

PRT3789	Degrader	98.08%
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.

HY-44012

SMARCA-BD ligand 1 for PROTAC	Ligand	99.07%
SMARCA-BD ligand 1 for PROTAC is a compound that binds to the BAF ATPase subunits SMARCA2, and used for degrading SMARCA2, based on PROTAC.

HY-44012B

SMARCA-BD ligand 1 for PROTAC hydrochloride	Ligand	99.24%
SMARCA-BD ligand 1 hydrochloride for PROTAC is a compound that binds to the BAF ATPase subunits SMARCA2, and used for degrading SMARCA2, based on PROTAC.

HY-185075

FHD-909	Inhibitor
FHD-909 (LY4050784) is an orally active and selective SMARCA2 (BRM) ATPase inhibitor. FHD-909 potently inhibits purified BRM ATPase with an IC₅₀ of 0.0025 μM and exhibits 35.69-fold selectivity for BRM over purified SMARCA4 (BRG1) ATPase. FHD-909 induces synthetic lethality, suppresses cell proliferation, modulates target gene expression, and achieves remarkable tumor growth inhibition and regression in SMARCA4-mutant cancer cells and xenograft models. FHD-909 can be used for the research of SMARCA4/BRG1-mutant cancers, advanced solid tumors, and BAF complex-related disorders.

HY-181909

PROTAC SMARCA2 degrader-36	Degrader
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.

HY-180960

NEP202	Degrader
NEP202 is a SMARCA2 PROTAC degrader designed based on the GID4 E3 ligase. NEP168 can be used for cancer research.

HY-44012A

SMARCA-BD ligand 1 for PROTAC dihydrochloride	Ligand	98.08%
SMARCA-BD ligand 1 for PROTAC dihydrochloride is a compound that binds to the BAF ATPase subunits SMARCA2, and used for degrading SMARCA2, based on PROTAC.

HY-170824

SMD-3236	Degrader
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.

HY-168230

SMARCA2 ligand-9	Ligand
SMARCA2 ligand-9 is the ligand of SMARCA2. SMARCA2 ligand-9 can be used to synthesize PROTAC SMARCA2 degrader-27 (HY-168229).

HY-176871

PROTAC SMARCA2 degrader-35	Degrader
PROTAC SMARCA2 degrader-35 (Compound 43) is a selective SMARCA2 PROTAC degrader with a DC₅₀ < 0.1 μM for SMARCA2. PROTAC SMARCA2 degrader-35 has anticancer activity and regulates cancer cell proliferation and growth through cell cycle arrest and DNA replication inhibition in SMARCA4-deleted cancer cells.

HY-44824

SMARCA2 ligand-13	Ligand
SMARCA2 ligand-13 is a PROTAC target protein ligand (Ligand for Target Protein for PROTAC). SMARCA2 ligand-13 can be used for synthesis PROTACs.

HY-180932

SMARCA2 ligand-17	Ligand
SMARCA2 ligand-17 (compound) is a SMARCA2 ligand. SMARCA2 ligand-17 can be used as a target protein ligand for PROTACs, for example, in the development and design of PROTAC SMARCA2 degraders such as PROTAC A515 (HY-180931). SMARCA2 ligand-17 can be used in cancer research.

HY-181910

SMARCA2 ligand-19	Ligand
SMARCA2 ligand-19 (Compound 26a) is a ligand for the target protein for PROTAC (SMARCA2). SMARCA2 ligand-19 can be used to synthesize PROTACs, such as SMARCA2 degrader-36 (HY-181909).

HY-161885

SMARCA2/4-IN-4	Inhibitor
SMARCA2-IN-6 is a SMARCA2 and SMARCA4 inhibitor, with an IC₅₀ value of <0.005 μM for both SMARCA2 and SMARCA4. SMARCA2-IN-6 exerts anticancer activity against BRG1-mutant melanoma. SMARCA2-IN-6 can be used for research related to Brg1/Smarca4-mutant cancers.

HY-170817

SMI-1074	Inhibitor
SMI-1074, a SMARCA bromodomain inhibitor, is a PROTAC target protein ligand (Ligand for Target Protein for PROTAC). SMI-1074 can be used for synthesis SMD-3236 (HY-170824) and SMD-1087 (HY-170828). SMI-1074 can be used for the research of smarca4-deficient cancers.

HY-180931

PROTAC A515	Degrader
PROTAC A515 is a SMARCA2 PROTAC degrader. PROTAC A515 promotes the ubiquitination and degradation of SMARCA2. PROTAC A515 can be used in cancer research.

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