BRD-K98645985
目录号 : GC39238
BRD-K98645985是一种BAF（mammalian SWI/SNF）转录阻遏的抑制剂。
Cas No.:1357647-78-9
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | HCT116 cells |
Preparation Method | HCT116 cells were grown in McCoy’s 5a media supplemented with 10% FBS. Viability assays were performed in 384-well plates. Cells were plated at 500 cells/well. 24h after seeding, cells were treated with all possible combinations of 5 doses of both VE-821 (1.25–20µM) and BRD-K98645985 (1.25–20µM) for a total of 25 total combinations in 8 replicates. The media containing fresh drug was replaced every 48h. After 5 days, cellular viability was measured and combination index values were calculated utilizing R. |
Reaction Conditions | 1.25-20µM; 5 days |
Applications | Combination of BRD-K98645985 with VE-821 synergistically reduced cell viability in HCT116 cells. |
| Animal experiment [2]: | |
Animal models | female nonobese diabetic (NOD)/severe combined immunodeficient (SCID) mice |
Preparation Method | A 100μl suspension of 5×106 ARID1A KD and control DMS273 and H446 cells in an equal volume of Matrigel was injected subcutaneously in the dorsal flank of 4-week-old female nonobese diabetic (NOD)/severe combined immunodeficient (SCID) mice. Treatment was initiated when the mean tumor volume reached approximately 100mm3, with intraperitoneal administration of either PBS (vehicle control) or BRD-K98645985 (20mg/kg) every other day (Q2D). The tumor volume and body weight of the mice were measured every 2 to 3d. Tumor sizes were measured using a caliper, and tumor volumes were determined using the following equation: tumor volume [mm3] = (tumor length×tumor width2 )/2. After reaching the endpoint, the mice were euthanized. |
Dosage form | 20mg/kg; i.p.; every other day for 15 days |
Applications | BRD-K98645985 significantly reduced tumor volume and weight in ARID1A-deficient SCLC xenograft models. |
References: | |
| Cas No. | 1357647-78-9 | SDF | |
| Canonical SMILES | O=C(NC1=CC=C(OC[C@H](C)N(CC2=CC=C(C3=NC=CC=C3)C=C2)C[C@H](C)[C@@H](OC)CN(C)C4=O)C4=C1)NC(C)C | ||
| 分子式 | C33H43N5O4 | 分子量 | 573.73 |
| 溶解度 | DMSO : 250 mg/mL (435.75 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.743 mL | 8.7149 mL | 17.4298 mL |
| 5 mM | 348.6 μL | 1.743 mL | 3.486 mL |
| 10 mM | 174.3 μL | 871.5 μL | 1.743 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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