D-I03

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

D-I03 (D-103) 是一种小分子，在体外抑制 RAD52 介导的 ssDNA 退火，IC50 为 5 uM，与 RAD52 结合，Kd 为 25.8 uM，并抑制 D 环形成，IC50 为 8 uM。

D-I03 (D-103) is a small molecule that inhibits RAD52-mediated ssDNA annealing with IC50 of 5 uM, binds to RAD52 with Kd of 25.8 uM and inhibits D-loop formation with IC50 of 8 uM in vitro; suppresses growth of BRCA1- and BRCA2-deficient cells (at 2.5 uM concentration) and inhibits RAD52-mediated SSA in human U2OS cells; selective toward SSA over homologous recombination (HR).

D-I03 (0-10 μM; on days 1 and 3; Capan-1 and UWB1.289 cells) treatment preferentially suppressed the growth of Capan-1 and UWB1.289 cells in a concentration-dependent manner.?D-I03 inhibits RAD52 foci formation induced by cisplatin in BCR-ABL1-positive BRCA1-deficient 32Dcl3 murine hematopoietic cell line that expresses GFP-RAD52. In the presence of D-I03 (2.5 μM), the fraction of cells with RAD52 foci is decreased, from 38.7% to 171%; at the same time, the fraction of Cisplatin-treated cells without foci is increased from 48.4% to 71.9%. D-I03 does not effect on RAD51 foci induced by Cisplatin. Also, D-I03 alone induce neither RAD51 foci nor RAD52 foci (in BRCA1-deficient cells) indicating low genotoxicity of D-I03. Cell Proliferation Assay Cell Line:Capan-1 (BRCA2?) and UWB1.289 (BRCA1+) cells Concentration:0 μM, 2.5 μM, 5 μM, or 10 μMIncubation Time:On days 1 and 3Result:Preferentially suppressed the growth of Capan-1 and UWB1.289 cells.

D-I03 (50 mg/kg/day; intraperitoneal injection; daily; for 7 days; nu/nu mice) treatment reduces BRCA1-deficient MDA-MB-436 tumor growth. Talazoparib puls D-I03 does not affect the growth of BRCA1-proficient tumors and does not exert any significant toxicity against normal tissues and organs.Pharmacokinetic and toxicity studies indicates that maximal tolerated dose of D-I03 is ≥50 mg/kg, and t1/2 is 23.4 hours, resulting in >1 μM maximal concentration in peripheral blood. Animal Model:Nu/nu mice injected with BRCA1-deficient MDA-MB-436 cells Dosage:50 mg/kg/day Administration:Intraperitoneal injection; daily; for 7 days Result:Reduced BRCA1-deficient MDA-MB-436 tumor growth.

D103

Cell Cycle/DNA Damage

DNA Repair Protein

DNA Repair Protein

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688342-78-1

428.643

C23H36N6S

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (116.65 mM)

CCN1CCN(CC1)C2=NC3=C(C=C(C=C3)NC(=S)NCCN(CC)CC)C(=C2)C

1-(2-(diethylamino)ethyl)-3-(2-(4-ethylpiperazin-1-yl)-4-methylquinolin-6-yl)thiourea

(-20℃)

With Ice Pack

≥ 2 years