D-I03 是一种选择性的RAD52 抑制剂，Kd 为 25.8 μM。D-I03 抑制 RAD52 依赖性单链退火 (SSA) 和 D 环形成，IC50 分别为 5 μM 和 8 μM。D-I03 抑制 BRCA1 和 BRCA2 缺陷细胞的生长，并抑制顺铂诱导的 RAD52 病灶形成，但对 RAD51 无影响。

D-I03 is a selective RAD52 inhibitor with a Kd of 25.8 μM. D-I03 specifically inhibits RAD52-dependent single-chain annealing (SSA) and D-loop formation, with IC50 of 5 μM and 8 μM, respectively. D-I03 inhibited the growth of BRCA1 and BRCA2 deficient cells and inhibited the formation of damage-induced RAD52 foci, but does not effect on RAD51 foci induced by Cisplatin.

D-IO3 (0-10 μM; on Days 1 and 3; Capan-1 and UWB1.289 cells) treatment preferentially inhibited the growth of Capan-1 and UWB1.289 cells in a concentration-dependent manner . D-IO3 inhibited cisplatin-induced RAD52 foci formation in the BCR-ABL1-positive BRCA1-deficient 32Dcl3 mouse hematopoietic cell line expressing GFP-RAD52. In the presence of D-IO3 (2.5 μM), the proportion of cells with RAD52 lesions decreased from 38.7% to 171%; meanwhile, the proportion of cisplatin-treated cells without lesions increased from 48.4% to 71.9%. D-IO3 had no effect on cisplatin-induced RAD51 foci. Similarly, D-I03 alone (in BRCA1-deficient cells) induced neither RAD51 nor RAD52 lesions, indicating that D-I03 has low genotoxicity[1].

D-IO3 (50 mg / kg / day; intraperitoneal injection; daily; 7 consecutive days; nu / nu mice) treatment can reduce the growth of BRCA1-deficient MDA-MB-436 tumors. Talazoparib puls D-I03 does not cause any obvious toxicity to normal tissues and organs, and does not affect the growth of BRCA1-positive tumors. Pharmacokinetic and toxicity studies have shown that the maximum tolerated dose of D-I03 is ≥50mg / kg and t1 / 2 is 23.4 hours, resulting in a maximum concentration in peripheral blood>1μM[1].

688342-78-1

C23H36N6S

428.64

DI03

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