SMARCA2
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]
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SMARCA2 Related Products (61)
Related Products (61)
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AU-15330
0 ImagesAU-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.
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AU-24118
0 ImagesAU-24118 is an orally active PROTAC degrader that recruits cereblon to target the degradation of SMARCA2, SMARCA4 and PBRM1. AU-24118 impairs the chromatin accessibility of oncogenic transcription factors, inhibits colony formation, dislodges chromatin-bound transcription factors, attenuates downstream signal transduction, induces apoptosis, and exerts antiproliferative and cytotoxic effects. AU-24118 can be used in research related to castration-resistant prostate cancer, colorectal cancer, small cell lung cancer and multiple myeloma (including the t (4;14) subtype).
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PRT3789
0 ImagesPRT3789 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.
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FHD-909
0 ImagesCat. No.: HY-185075CAS No.: 3008577-34-9Synonyms: LY4050784FHD-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.
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SMD-6346
0 ImagesCat. No.: HY-184673CAS No.: 3086248-19-0SMD-6346 is an orally active SMARCA2 PROTAC degrader with a DC50 of 3.3 nM. SMD-6346 induces SMARCA2 degradation and exhibits extremely low activity against SMARCA4. SMD-6346 inhibits the growth of SMARCA4-deficient cancer cells and suppresses tumor growth in mouse xenograft models. SMD-6346 can be used for the research of non-small cell lung cancer.
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YD54
0 ImagesYD54 is an orally active and selective SMARCA2 PROTAC degrader. YD54 induces SMARCA4 degradation but with low potency and selectivity. YD54 selectively inhibits the growth of various cancer cells and suppresses tumor growth in mouse xenograft models. YD54 can be used for the research of SMARCA4-mutant lung cancer.
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PROTAC SMARCA2 degrader-8
0 ImagesPROTAC SMARCA2 degrader-8 is a SMARCA2 PROTAC degrader with a DC50 of 28 nM in A375 cells. PROTAC SMARCA2 degrader-8 forms a crystallizable ternary complex with the SMARCA4 bromodomain and VBC, promoting the ubiquitination and proteasomal degradation of SMARCA2. PROTAC SMARCA2 degrader-8 can be used in melanoma research.
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A947
0 ImagesCat. No.: HY-148381CAS No.: 2378056-80-3A947 is a VHL-based SMARCA2 PROTAC degrader with a DC50 of 39 pM and a Kd of 93 nM for human SMARCA2. A947 recruits SMARCA2 to the VHL E3 ubiquitin ligase for ubiquitination modification, mediates its degradation via the proteasome, and exerts selective degradation effects on SMARCA4 and PBRM1. A947 induces G1 cell cycle arrest, inhibits transcription, and exerts growth inhibitory effects in SMARCA4G12C-mutant cancer cells. A947 acts synergistically with MCL1 inhibitors to induce apoptosis in SMARCA4G12C-mutant cancer cells. A947 can be used in studies related to SMARCA4G12C-mutant non-small cell lung cancer and non-small cell lung cancer.
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SMD-3236
0 ImagesCat. No.: HY-170824CAS No.: 3033586-31-8SMD-3236 is a SMARCA2 PROTAC degrader with a DC50 of 0.5 nM, a Dmax 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.
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PXR Ligand 2
0 ImagesCat. No.: HY-169280CAS No.: 3059971-00-2
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SMARCA2 ligand-9
0 ImagesCat. No.: HY-168230CAS No.: 1997320-33-8
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SMARCA2 ligand-10
0 ImagesCat. No.: HY-168237CAS No.: 3024271-84-6
