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 (68)
Related Products (68)
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PROTAC SMARCA2 degrader-36
0 ImagesCat. No.: HY-181909PROTAC 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.
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PROTAC SMARCA2/4 degrader-36
0 ImagesCat. No.: HY-170347CAS No.: 3033588-00-7PROTAC SMARCA2/4 degrader-36 is a bifunctional PROTAC degrader that degrades SMARCA2 and SMARCA4. PROTAC SMARCA2/4 degrader-36 hijacks the ubiquitin-proteasome system to mediate the degradation of SMARCA2/4 by binding to the VHL E3 ubiquitin ligase. PROTAC SMARCA2/4 degrader-36 downregulates SMARCA2/4 in tumor tissues in mouse xenograft models. PROTAC SMARCA2/4 degrader-36 can be used in studies related to non-small cell lung cancer.
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PROTAC SMARCA2 degrader-25
0 ImagesCat. No.: HY-169276CAS No.: 2770571-17-8PROTAC SMARCA2 degrader-25 is a PROTAC degrader targeting SMARCA2. PROTAC SMARCA2 degrader-25 is applicable to the research of smarca4-deficient cancers and multiple myeloma.
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PROTAC SMARCA2/4 degrader-25
0 ImagesCat. No.: HY-162813PROTAC SMARCA2/4 degrader-25 is a selective SMARCA2/SMARCA4 PROTAC degrader with selective anti-tumor activity. PROTAC SMARCA2/4 degrader-25 is activated by endogenous GSH, forms a ternary complex with SMARCA2 or SMARCA4 and VHL E3 ubiquitin ligase, and mediates degradation via the proteasome pathway. PROTAC SMARCA2/4 degrader-25 induces DNA damage and apoptosis, and inhibits cancer cell proliferation. PROTAC SMARCA2/4 degrader-25 is applicable to lung cancer-related research.
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PROTAC SMARCA2/4 degrader-39
0 ImagesCat. No.: HY-178225CAS No.: 3099581-74-2
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PROTAC SMARCA2/4 degrader-32
0 ImagesCat. No.: HY-159459CAS No.: 2568273-79-8
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PROTAC SMARCA2 degrader-35
0 ImagesCat. No.: HY-176871CAS No.: 3032998-97-0PROTAC 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.
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SMD-1087
0 ImagesCat. No.: HY-170828CAS No.: 3033586-04-5SMD-1087 is a VHL-recruiting SMARCA2 PROTAC degrader with a DC50 of 8 nM. SMD-1087 induces ubiquitination and degradation of SMARCA2 via the proteasome pathway. SMD-1087 reduces PBRM1 protein levels, inhibits the growth of SMARCA4-deficient cancer cells, and suppresses tumor growth in mouse xenograft models. SMD-1087 can be used for research on SMARCA4-deficient human cancers, including lung cancer and melanoma.
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LO-3-62
0 ImagesCat. No.: HY-175186LO-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 CUL4DCAF16 E3 ubiquitin ligase, inducing proteasome-dependent degradation of SMARCA2/4. LO-3-62 can be used in studies of monocytic leukemia.
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PROTAC SMARCA2 degrader-31
0 ImagesCat. No.: HY-168234CAS No.: 2380274-45-1PROTAC SMARCA2-degrader-36 is a PROTAC degrader of SMARCA2, achieving a 99% degradation rate in H929 cells. It also exhibits degradative activity against SMARCA4, but with relatively weaker efficacy. PROTAC SMARCA2-degrader-36 can inhibit cancer cell proliferation and may be used in research related to multiple myeloma.
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PROTAC SMARCA2 degrader-32
0 ImagesCat. No.: HY-170343CAS No.: 3033586-50-1PROTAC 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.
