| Chemical Properties | Back Directory | [Boiling point ]
582.0±60.0 °C(Predicted) | [density ]
1.147±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: ≥ 100 mg/mL (233.30 mM) | [form ]
Solid | [pka]
12.00±0.70(Predicted) | [color ]
Off-white to light yellow | [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]
S=C(NCCN(CC)CC)NC1=CC2=C(C=C1)N=C(N3CCN(CC)CC3)C=C2C |
| Hazard Information | Back Directory | [Uses]
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]. | [Biological Activity]
D-I03 is a selective inhibitor of RAD52 with a corresponding Kd value of 25.8 μM. D-I03 inhibits ssDNA annealing via RAD52 and D-loop formation with IC50 values of 5 μM and 8 μM, respectively. | [in vitro]
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 < tr> | Cell Line: | Capan-1 (BRCA2 ? ) and UWB1 .289 (BRCA1 + ) cells | | Concentration: | 0 μM, 2.5 μM, 5 μM, or 10 μM | | Incubation Time: | On days 1 and 3 | td> | Result: | Preferentially suppressed the growth of Capan-1 and UWB1.289 cells. | < /tr> | [in vivo]
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 indicate that maximal tolerated dose of D-I03 is ≥50 mg /kg, and t 1/2 is 23.4 hours, resulting in >1 μM maximal concentration in peripheral blood. < div class="cpd-mod-vv"> | 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. | | [target]
| Target | Value | RAD52
(Cell-free assay) | 25.8 μM(Ki) |
| [References]
[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. DOI:10.1093/nar/gkw087
[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. DOI:10.1016/j.chembiol.2017.08.027
[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. DOI:10.1016/j.celrep.2018.05.034 |
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| Company Name: |
Wuhan Topule
|
| Tel: |
+86-02787215551 19945035818 |
| Website: |
www.topule.com/ |
| Company Name: |
InvivoChem
|
| Tel: |
13549236410 |
| Website: |
https://www.invivochem.cn/ |
|