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CAS No.: 1889279-16-6

A-485 Catalog No. CSN22658

A 485 is a potent and selective p300/CREB-binding protein (CBP) HAT domain inhibitor with IC50 of 2.6 and 9.8 nM for the CBP-bromodomain HAT-C/H3 (BHC) and p300-BHC domains, respectively.

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技术信息

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描述The histone acetyltransferase paralogs p300 and CBP (p300/CBP) are transcriptional co-activators, essential for a multitude of cellular events and the pathogenesis of multiple human diseases. A-485 is a potent, selective, drug-like p300/CBP catalytic inhibitor. It inhibited the activity of the p300-BHC (bromodomain-HAT-C/H3) domain and CBP-BHC with IC50 values of 9.8nM and 2.6nM, respectively. A-485 bound to p300-HAT with a K_D of 15±1nM. Treatment of prostate adenocarcinoma PC-3 cells with A-485 for 3h resulted in a concentration-dependent reduction in H3K27Ac with an EC₅₀ of 73nM. In androgen-dependent LnCaP-FGC cell line, treatment with A-485 for 7 and 24h decreased DHT-stimulated PSA expression more potently compared to AR antagonist enzalutamide. A-485 also downregulated 40% of DHT-responsive genes in androgen-depleted 22Rv1 cells. In male SCID mice, twice daily intraperitoneal injection of A-485 (twice per day) resulted in 54% tumor growth inhibition after 21 days of dosing as compared to vehicle-treated controls. Also, treatment with A-485 in tumor-bearing animals for 7 days decreased the mRNA levels of AR-dependent gene, SLC45A3, and c-Myc, at 3h after dosing^[1].
作用机制A-485 is a potent, selective p300/CBP inhibitor that binds to the catalytic active site of p300 and inhibits p300/CBP in an acetyl-CoA competitive manner. The methyl-urea of A-485 is inserted through the L1 loop where two hydrogen bonds are formed^[1].
参考文献

[1] Lasko LM, Jakob CG, Edalji RP, Qiu W, Montgomery D, Digiammarino EL, Hansen TM, Risi RM, Frey R, Manaves V, Shaw B, Algire M, Hessler P, Lam LT, Uziel T, Faivre E, Ferguson D, Buchanan FG, Martin RL, Torrent M, Chiang GG, Karukurichi K, Langston JW, Weinert BT, Choudhary C, de Vries P, Van Drie JH, McElligott D, Kesicki E, Marmorstein R, Sun C, Cole PA, Rosenberg SH, Michaelides MR, Lai A, Bromberg KD. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours. Nature. 2017 Oct 5;550(7674):128-132.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 1.8640 mL
- 9.3201 mL
- 18.6402 mL
- 5 mM
- 0.3728 mL
- 1.8640 mL
- 3.7280 mL
- 10 mM
- 0.1864 mL
- 0.9320 mL
- 1.8640 mL

技术信息

CAS号

1889279-16-6

储存条件

粉末: Sealed in dry,2-8°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C25H24F4N4O5

运输

蓝冰

分子量

536.48

别名

溶解度

DMSO	100.0 mg/mL (186.4 mM)
Water	Insoluble
Ethanol	100.0 mg/mL (186.4 mM)

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