For research use only. Not for therapeutic Use.
D-I03 is a selective RAD52 inhibitor with a Kd of 25.8 µM. D-I03 specifically inhibits RAD52-dependent single-strand annealing (SSA) and D-loop formation with IC50s of 5 µM and 8 µM, respectively. D-I03 suppresses growth of BRCA1- and BRCA2-deficient cells and inhibits formation of damage-induced RAD52 foci, but does not effect on RAD51 foci induced by Cisplatin[1][2].
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[1].?
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[1].
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[3].?
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[1].
| Catalog Number | I017625 |
| CAS Number | 688342-78-1 |
| Synonyms | 1-[2-(diethylamino)ethyl]-3-[2-(4-ethylpiperazin-1-yl)-4-methylquinolin-6-yl]thiourea |
| Molecular Formula | C23H36N6S |
| Purity | ≥95% |
| InChI | InChI=1S/C23H36N6S/c1-5-27(6-2)11-10-24-23(30)25-19-8-9-21-20(17-19)18(4)16-22(26-21)29-14-12-28(7-3)13-15-29/h8-9,16-17H,5-7,10-15H2,1-4H3,(H2,24,25,30) |
| InChIKey | UXDGHRWOHOPKIL-UHFFFAOYSA-N |
| SMILES | CCN1CCN(CC1)C2=NC3=C(C=C(C=C3)NC(=S)NCCN(CC)CC)C(=C2)C |
| Reference | [1]. Huang F, et al. Targeting BRCA1- and BRCA2-deficient cells with RAD52 small molecule inhibitors. Nucleic Acids Res. 2016 May 19;44(9):4189-99. [2]. Hengel SR, et al. Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy. Cell Chem Biol. 2017 Sep 21;24(9):1101-1119. [3]. Sullivan-Reed K, et al. Simultaneous Targeting of PARP1 and RAD52 Triggers Dual Synthetic Lethality in BRCA-Deficient Tumor Cells. Cell Rep. 2018 Jun 12;23(11):3127-3136. |
