YCH1899, an orally active PARP inhibitor, demonstrates potent inhibition of PARP1/2 with an IC50 of less than 0.001 nM. It shows marked antiproliferative efficacy against Olaparib-resistant (Capan-1/OP) and Talazoparib-resistant (Capan-1/TP) cells with IC50 values of 0.89 nM and 1.13 nM, respectively. Moreover, YCH1899 possesses favorable pharmacokinetic attributes in rats [1].

ARTD10/PARP10:10.8 nM, PARP15:51.623 nM, PARP2:<0.001 nM, PARP3:1.1 nM, PARP14:35.914 μM, PARP1:<0.001 nM, PARP7:7.3 nM, TNKS1:3.8 nM (EC50), TNKS2:12.4 nM, PARA6:9.5 nM, PARA11:2.166 μM, PARP12 (human):14.1 nM, PARP4:1.0 nM

YCH1899在7天的处理时间里，显著抑制了Capan-1、Capan-1/OP、Capan-1/TP细胞的增殖，其IC 50值分别为0.10、0.89、1.13 nM [1]。YCH1899 (0.001-1 nM, 4 h)增强PARP1-DNA复合物的稳定性，并抑制PARP形成 [1]。YCH1899在3.5小时的处理期内能够抑制BRCA突变/野生型细胞(V−C8, V79, HCT-15, HCC1937)的增殖，IC 50s范围为1.19-44.24 nM [1]。YCH1899 (1 μM, 24 h)在Capan-1、Capan-1/OP、Capan-1/TP细胞内诱导DNA损伤，导致γH2AX水平显著上升 [1]。此外，YCH1899 (1 μM, 48 h) 明显减弱了U2OS-DR-GFP细胞的同源重组(Homologous Recombination, HR)修复活性 [1]。

YCH1899在以5 mg/kg剂量静脉给药时，表现出中等清除力[1]。此外，YCH1899对MDA-MB-436/OP (dosages of 6.25, 12.5, 和 25 mg/kg, 每日口服一次，连续27天)和Capan-1/R (dosages of 12.5 和 25 mg/kg, 每日口服一次，连续21天)的异种移植小鼠模型表现出克服Talazoparib耐药性的效果，使肿瘤体积显著减少[1]。