INO-1001是一种 isoindolinone 衍生物，是一种强效的核酶聚（ADP-核糖）聚合酶（PARP）抑制剂，具有化学增敏和辐射增敏特性。INO-1001 抑制 PARP，可能通过抑制肿瘤细胞的 DNA 修复机制，进而减少肿瘤细胞对化疗和放疗的耐药性。PARP 酶被 DNA 断裂激活，参与单链 DNA 断裂的修复。
INO-1001, a potent and selective poly (ADP-ribose) polymerase (PARP) inhibitor, heightens radiation sensitivity and augments radiation-induced cell death by disrupting DNA repair mechanisms, leading to necrotic cell demise[1]. INO-1001 exhibits anti-tumor effects[2].
体外研究
INO-1001 demonstrates an IC50 of 0.05 μM in Chinese hamster ovary AA8 (CHO) cells[1].
INO-1001 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Transgenic R6/2 mice
Huntington's disease model
Intraperitoneal injection
10 mg/kg/day
Daily, starting from 4 weeks of age
INO-1001-treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the vehicle treated ones. Striatal atrophy was reduced, and there was a significant increase in activated CREB and BDNF in the striatal spiny neurons.
PLoS One. 2015 Aug 7;10(8):e0134482
Mice
R6/2 mouse model
Intraperitoneal injection
10 mg/kg/day
Twice daily, starting from 4 weeks of age until sacrifice
To investigate the effects of PARP-1 inhibition on CBP localization, by reducing CBP sequestration into the NIIs, and thus decreasing cellular toxicity resulting from it. Moreover, we studied the effects of the compound on calretinin and parvalbumin containing striatal cells, two subsets of interneurons that are particularly vulnerable to HD.
搜索
