Evo312 is an inhibitor of protein kinase C beta I (PKCβI) with an IC50 of 117.34 nM and exhibits dose-dependent characteristics. It acts by inhibiting the expression of the PKCβI protein, which leads to cell cycle arrest and apoptosis in PANC-GR (gemcitabine-resistant pancreatic cancer cells). Evo312 also demonstrates antiproliferative effects in pancreatic cancer cells PANC-1 and PANC-GR, with IC50 values of 0.08 μM and 0.07 μM respectively, while presenting an IC50 of 2.95 μM in normal human pancreatic ductal epithelial cells HPDE6-c7. Additionally, Evo312 has shown antitumor activity in a mouse xenograft model using PANC-GR cells.

PKCβ1:117.34 nM

Evo312 在不同浓度(0-160 nM，24 h)处理下，显著抑制PANC-GR细胞中的PKCβ1蛋白表达及其下游靶蛋白的磷酸化；此外，Evo312还能诱导G2/M细胞周期阻滞，抑制有丝分裂。在长时间处理(0-160 nM，48 h)后，Evo312诱导PANC-GR细胞进入凋亡过程。

Evo312（5 mg/kg，i.p.，每周三次，20天）在异种移植小鼠模型中下调PKCβⅠ，从而抑制了PANC-GR（吉西他滨耐药细胞）的肿瘤生长；相比之下，吉西他滨对肿瘤生长的影响几乎可以忽略。