BRD-K98645985 is an inhibitor of BAF (mammalian SWI/SNF) transcriptional repression[1]. BAF complex is a mammalian chromatin remodeling complex that belongs to the SWI/SNF family and regulates gene expression by altering chromatin structure, playing key roles in gene transcription, DNA repair, and cell differentiation[2]. ARID1A is a protein containing an AT-rich interaction domain and is a key subunit of the BAF complex[3]. BRD-K98645985 prevents nucleosome localization by binding to the ARID1A-specific BAF complex and is usually used in research of HIV-1 latency reversal and cancer therapy[4][5].
In vitro, combination of BRD-K98645985 (1.25-20µM; 5 days) with VE-821 synergistically reduced cell viability in HCT116 cells[6].
In vivo, BRD-K98645985 (20mg/kg; i.p.; every other day for 15 days) significantly reduced tumor volume and weight in ARID1A-deficient SCLC xenograft models[7].
References:
[1] Marian CA, Stoszko M, Wang L, et al. Small Molecule Targeting of Specific BAF (mSWI/SNF) Complexes for HIV Latency Reversal. Cell Chem Biol. 2018;25(12):1443-1455.e14.
[2] Centore RC, Sandoval GJ, Soares LMM, Kadoch C, Chan HM. Mammalian SWI/SNF Chromatin Remodeling Complexes: Emerging Mechanisms and Therapeutic Strategies. Trends Genet. 2020;36(12):936-950.
[3] Mullen J, Kato S, Sicklick JK, Kurzrock R. Targeting ARID1A mutations in cancer. Cancer Treat Rev. 2021;100:102287.
[4] Tomar S, Ali I, Ott M. A BAF'ling Approach to Curing HIV. Cell Chem Biol. 2018;25(12):1441-1442.
[5] Wanior M, Krämer A, Knapp S, Joerger AC. Exploiting vulnerabilities of SWI/SNF chromatin remodelling complexes for cancer therapy. Oncogene. 2021;40(21):3637-3654.
[6] Chory EJ, Kirkland JG, Chang CY, et al. Chemical Inhibitors of a Selective SWI/SNF Function Synergize with ATR Inhibition in Cancer Cell Killing. ACS Chem Biol. 2020;15(6):1685-1696.
[7] Cao G, Ma L, Xueqin Dai, et al. ARID1A Governs Genomic Stability and Proliferation in SCLC via c-MYC/PARP1 Suppression Driving Vulnerability to BET Inhibitors. Research (Wash D C). 2025;8:0908.
BRD-K98645985是一种BAF（mammalian SWI/SNF）转录阻遏的抑制剂[1]。BAF复合物是一种哺乳动物的染色质重塑复合物，属于SWI/SNF家族，可通过改变染色质结构来调控基因表达，在基因转录、DNA修复和细胞分化等过程中发挥重要作用[2]。ARID1A是一种含有AT富集结合域的蛋白，是BAF复合物的一个关键亚基[3]。BRD-K98645985通过结合ARID1A特异的BAF复合物，阻止核小体定位，常用于HIV-1潜伏期逆转、癌症治疗等研究[4][5]。
体外实验中，BRD-K98645985（1.25-20µM；处理5天）与VE-821联合使用，在HCT116细胞中协同降低了细胞活力[6]。
体内实验中，BRD-K98645985（20mg/kg；腹腔注射；每两天一次，持续15天）显著减少了ARID1A缺失的小细胞肺癌（SCLC）异种移植模型中的肿瘤体积和重量[7]。