GNE-272

GNE-272 is a potent and selective inhibitor of cyclic AMP response element binding protein (CBP), an inhibitor of E1A binding protein p300 (EP300), with IC₅₀ values of 0.02 and 0.03μM, respectively. It is also an in vivo probe of CBP/EP300 bromodomains^{[1, 2]}. GNE-272 can be used to study acute myeloid leukemia, multiple myeloma and inflammatory diseases^{[3, 4]}.

In vitro, GNE-272 (5μM) treatment of human cancer cell lines (MOLM-16, HL-60, LP-1, KMS-34, Pfeiffer, DOHH-2 cells) for 4h significantly inhibited the expression of the proto-oncogene MYC at both RNA and protein levels^[1].

In vivo, GNE-272 (12.5, 25, 50mg/kg) was orally treated with MOLM-16 cell xenograft mice for 21 days and exerted antitumor effects in mice in a dose-dependent manner, with tumor growth inhibition rates (%TGI) of 46%, 65%, and 102% at 12.5, 25, and 50mg/kg, respectively^[1].

References:
[1] Crawford T D, Romero F A, Lai K W, et al. Discovery of a potent and selective in vivo probe (GNE-272) for the bromodomains of CBP/EP300[J]. Journal of medicinal chemistry, 2016, 59(23): 10549-10563.
[2] Romero F A, Murray J, Lai K W, et al. GNE-781, a highly advanced potent and selective bromodomain inhibitor of cyclic adenosine monophosphate response element binding protein, binding protein (CBP)[J]. Journal of Medicinal Chemistry, 2017, 60(22): 9162-9183.
[3] Gosselé K, Latino I, Laul E, et al. Development of a novel class of CBP/EP300 bromodomain inhibitors which block TNF-α induced NFκB signaling[J]. 2024.
[4] Masci D, Puxeddu M, Silvestri R, et al. Targeting CBP and p300: Emerging Anticancer Agents[J]. Molecules, 2024, 29(19): 4524.

GNE-272是一种有效和选择性的环磷酸腺苷反应元件结合蛋白（CBP）抑制剂，是E1A结合蛋白p300（EP300）的抑制剂，IC₅₀值分别为0.02和0.03μM，也是CBP/EP300溴结构域体内探针^{[1, 2]}。GNE-272能够用于研究急性髓系白血病、多发性骨髓瘤及炎症性疾病^{[3, 4]}。

在体外，GNE-272（5μM）处理人类癌症细胞系（MOLM-16, HL-60, LP-1, KMS-34, Pfeiffer, DOHH-2细胞）4h，在RNA和蛋白质水平上均显著抑制了原癌基因MYC的表达^[1]。

在体内，GNE-272（12.5, 25, 50mg/kg）通过口服治疗MOLM-16细胞异种移植小鼠21天，以剂量依赖性方式在小鼠体内发挥抗肿瘤作用，在12.5、25、50mg/kg时肿瘤生长抑制率（%TGI）分别为46%、65%、102%^[1]。