| Description | ETP-46321 is an effective and orally bioavailable PI3Kα/PI3Kδ inhibitor (Ki: 2.3/14.2 nM). |
| In vitro | ETP-46321已经经过特性分析，显示出对PI3K α和δ的强效抑制作用，并且与mTOR及288种代表性激酶相比具有高度选择性。ETP-46321还针对在人类癌症中检测到的三种p110α突变酶（E542K、E545K和H1047R）进行了测试，与野生型蛋白相比，对这些突变体的抑制作用同样有效（对PI3Kα-H1047R、PI3Kα-E545K和PI3Kα-E542K的Kiapp分别为2.33、1.77和1.89 nM）。ETP-46321还能抑制U2OS细胞系中AKT的磷酸化（IC50：8.3 nM）。 |
| In vivo | ETP-46321因其在BALB-C小鼠中展现出的良好药代动力学特性、低体内清除率(0.6 L/h/Kg)及高口服生物利用度(90%)，被选用于活体研究。在携带K-RasG12V致癌突变的肺瘤小鼠模型的初步体内评估中，ETP-46321展示出显著的肿瘤生长抑制作用，证明了其优良的药代动力学特性。 |
| Animal experiments | BALB/C mice are treated daily with ETP-46321 (50 mg/kg, p.o.) for three weeks. Tumor volumes of four mice in each treatment group are measured and compared to the starting volume at the beginning of the treatment. |
| Target activity | p110β:170 nM (Ki), PI3Kα (H1047R):2.33 nM (Ki), PI3Kα (E542K):1.77 nM (Ki), p110δ:14.2 nM (Ki), PI3Kα (E542K):1.89 nM (Ki), p110γ:179 nM (Ki), p110α:2.3 nM (Ki) |
| molecular weight | 473.55 |
| Molecular formula | C20H27N9O3S |
| CAS | 1252594-99-2 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 30 mg/mL (63.35 mM) |
| References | 1. Martínez González S, et al. Identification of ETP-46321, a potent and orally bioavailable PI3K α, δ inhibitor. Bioorg Med Chem Lett. 2012 May 15;22(10):3460-6. |