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A1874

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Chemical Structure| 2064292-12-0 同义名 : -
CAS号 : 2064292-12-0
货号 : A1147982
分子式 : C58H62Cl3F2N9O7S
纯度 : 99%+
分子量 : 1173.59
MDL号 : MFCD31813733
存储条件：

粉末 Keep in dark place,Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 145 mg/mL(123.55 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
描述 A1874 is a nutlin-based PROTAC targeting on BRD4, consist of a BRD4-ligand JQ1 linked to a MDM2 E3 ligase ligand RG7388. A1874 possesses dual function as it dose-dependently degraded its target BRD4, accompanied with the downregulation of c-MYC, as well as stabilization of P53 and upregulated P21 due to the efficient engagement of MDM2 by RG7388 in HCT116 cells exposure to A1874 at concentration ranging in 100nM-10μM post 24h. A1874 at concentration of 100nM achieved a near-maximum degradation of BRD4 by 98%. Incubation with A1874 ultimately resulted in a 97% loss in HCT116 cell viability, much more potent than JQ1 or RG7388 alone, for a synergistic antiproliferative effect by the combination of the E3 ligase ligand and targeting warhead. It seems that the potency to cell viability of A1874 may corelate to the status of P53 as A1874 was less potent against the cell line with mutant P53 or P53 depletion. A1875 is the inactive version of A1874[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

0.85mL

0.17mL

0.09mL

4.26mL

0.85mL

0.43mL

8.52mL

1.70mL

0.85mL
参考文献

[1]Hines J, Lartigue S, et al. MDM2-Recruiting PROTAC Offers Superior, Synergistic Antiproliferative Activity via Simultaneous Degradation of BRD4 and Stabilization of p53. Cancer Res. 2019 Jan 1;79(1):251-262.