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Pelabresib

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Chemical Structure| 1380087-89-7 同义名 : CPI-0610
CAS号 : 1380087-89-7
货号 : A137689
分子式 : C20H16ClN3O2
纯度 : 98%
分子量 : 365.813
MDL号 : MFCD28144505
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(287.03 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

  • BET

    BRD4-BD1, IC50:39 nM
描述 The Bromodomain and Extra-Terminal Domain (BET) family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. It can play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones. CPI-0610 is a potent and selective benzoisoxazoloazepine BET bromodomain inhibitor with IC50 value of 39nM in a BRD4-BD1 TR-FRET assay. It effectively reduced the expression of downstream target MYC on RNA level in MV-4-11 cells with EC50 value of 180nM. Similarly, this downregulation of MYC could be also observed in vivo at dose of 15mg/kg, BID. Oral administration of CPI-0610 effectively inhibited MV-4-11 tumor growth in mouse xenograft at dose of 60mg/kg, QD or 30mg/kg, BID. Also, it synergized the tumor growth suppression of doxorubicin (2 mg/kg, IV, BIW) at dose of 10mg/kg, SC, BID. CPI-0610 treatment resulted in MM cytotoxicity at dose ranging in 200-1500nM post 72h in vitro by inducing G1 cell cycle arrest and caspase-dependent apoptosis. CPI-0610 significantly delayed tumor growth and increased the survival of MM-bearing SCID mice in a xenograft model at dose of 10mg/kg (dissolved in 0.5% (w/v) methylcellulose), SC, BID.
作用机制 CPI-0610 could bind in the acetyl-lysine recognition site and make direct hydrogen-bonding interactions with Asn140 of the target protein.[1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.73mL

0.55mL

0.27mL

13.67mL

2.73mL

1.37mL

27.34mL

5.47mL

2.73mL
参考文献

[1]Albrecht BK, Gehling VS, et al. Identification of a Benzoisoxazoloazepine Inhibitor (CPI-0610) of the Bromodomain and Extra-Terminal (BET) Family as a Candidate for Human Clinical Trials. J Med Chem. 2016 Feb 25;59(4):1330-9.

[2]Siu KT, Ramachandran J, et al. Preclinical activity of CPI-0610, a novel small-molecule bromodomain and extra-terminal protein inhibitor in the therapy of multiple myeloma. Leukemia. 2017 Aug;31(8):1760-1769.