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A-485

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Chemical Structure| 1889279-16-6 同义名 : -
CAS号 : 1889279-16-6
货号 : A732746
分子式 : C25H24F4N4O5
纯度 : 99%+
分子量 : 536.476
MDL号 : MFCD31619258
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(223.68 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • p300/CBP

    p300 HAT, IC50:0.06 μM
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 KD 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].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.86mL

0.37mL

0.19mL

9.32mL

1.86mL

0.93mL

18.64mL

3.73mL

1.86mL
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.