D-I03
- CAS No.
- 688342-78-1
- Chemical Name:
- D-I03
- Synonyms
- D-I03;D-I03 (D103);D-I03, 10 mM in DMSO;1-(2-(Diethylamino)ethyl)-3-(2-(4-ethylpiperazin-1-yl)-4-methylquinolin-6-yl)thiourea;Thiourea, N-[2-(diethylamino)ethyl]-N'-[2-(4-ethyl-1-piperazinyl)-4-methyl-6-quinolinyl]-
- CBNumber:
- CB44844707
- Molecular Formula:
- C23H36N6S
- Molecular Weight:
- 428.64
- MDL Number:
- MOL File:
- 688342-78-1.mol
- MSDS File:
- SDS
| Product description | Number | Pack Size | Price |
| D-I03 ≥98% (HPLC) | SML2496 | 5mg | $113 |
| D-I03 ≥98% (HPLC) | SML2496 | 25mg | $454 |
| D-I03 99.73% | CS-0087335 | 5mg | $80 |
| D-I03 99.73% | CS-0087335 | 10mg | $145 |
| D-I03 99.73% | CS-0087335 | 25mg | $330 |
| 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 |
| UNSPSC Code | 12352200 |
| NACRES | NA.77 |
D-I03 price More Price(5)
| Manufacturer | Product number | Product description | CAS number | Packaging | Price | Updated | Buy |
|---|---|---|---|---|---|---|---|
| Sigma-Aldrich | SML2496 | D-I03 ≥98% (HPLC) | 688342-78-1 | 5mg | $113 | 2026-03-19 | Buy |
| Sigma-Aldrich | SML2496 | D-I03 ≥98% (HPLC) | 688342-78-1 | 25mg | $454 | 2026-03-19 | Buy |
| ChemScene | CS-0087335 | D-I03 99.73% | 688342-78-1 | 5mg | $80 | 2021-12-16 | Buy |
| ChemScene | CS-0087335 | D-I03 99.73% | 688342-78-1 | 10mg | $145 | 2021-12-16 | Buy |
| ChemScene | CS-0087335 | D-I03 99.73% | 688342-78-1 | 25mg | $330 | 2021-12-16 | Buy |
D-I03 Chemical Properties,Uses,Production
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
| 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
D-I03 Preparation Products And Raw materials
Raw materials
Preparation Products
D-I03 Suppliers
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| TargetMol Chemicals Inc. | +1-781-999-5354; +17819995354 | marketing@targetmol.com | United States | 32469 | 58 |
| TargetMol Chemicals Inc. | +1-781-999-5354; | support@targetmol.com | United States | 39042 | 58 |
| Wuhan Topule Biopharmaceutical Co., Ltd | +8618327326525 | masar@topule.com | China | 8467 | 58 |
| Aladdin Scientific | tp@aladdinsci.com | United States | 57505 | 58 | |
| SHANGHAI FORTUNE CHEMICAL TECHNOLOGY CO., LTD | 13816107857 | sales@fortunechem-sh.com | China | 984 | 58 |
| Shanghai Beckham Medical Technology Co., Ltd | 13816613772 | huahero21@sina.com | China | 2528 | 55 |
| Shanghai YuanYe Biotechnology Co., Ltd. | 021-61312847; 18021002903 | 3008007409@qq.com | China | 86249 | 60 |
| ShangHai Biochempartner Co.,Ltd | 177-54423994 17754423994 | 2853530910@QQ.com | China | 8000 | 62 |
| Changzhou Chenhong Biotechnology Co., Ltd. | +86-0519-85788828 +86-13775037613 | sales@chemrenpharm.com | China | 4032 | 58 |
| ChemeGen(Shanghai) Biotechnology Co.,Ltd. | 18818260767 | sales@chemegen.com | China | 11218 | 58 |
