| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
RAD52 ( Ki = 25.8 µM )
D-I03 primarily targets RAD52, a protein involved in the homologous recombination (HR) DNA repair pathway that is important for maintenance of genome integrity. RAD52 plays a critical role in repairing DNA double-strand breaks, particularly in BRCA1/2-deficient cells where it becomes essential for survival. By inhibiting RAD52 with a Kd of 25.8 μM, D-I03 blocks RAD52-dependent DNA repair mechanisms including SSA and D-loop formation. |
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| ln Vitro |
D-I03 (0-10 μM; on days 1 and 3; Capan-1 and UWB1.289 cells) treatment preferentially inhibited the growth of UWB1.289 and Capan-1 cells in a concentration-dependent manner[1].
D-I03 inhibits the formation of RAD52 foci in BCR-ABL1-positive, BRCA1-deficient 32Dcl3 murine hematopoietic cell line, which expresses GFP-RAD52, in response to cisplatin. The percentage of cells with RAD52 foci drops from 38.7% to 171% in the presence of D-I03 (2.5 μM); concurrently, the percentage of cells treated with ciprofloxacin without foci rises from 48.4% to 71.9%. ? D-I03 has no effect on RAD51 foci that are brought on by cisplatin. D-I03 exhibits low genotoxicity as evidenced by its inability to induce either RAD51 or RAD52 foci in BRCA1-deficient cells when used alone [1]. In vitro, D-I03 functions as a selective RAD52 inhibitor with a Kd of 25.8 μM. It specifically inhibits RAD52-dependent single-strand annealing (SSA) and D-loop formation with IC50 values of 5 μM and 8 μM, respectively. D-I03 suppresses the growth of BRCA1- and BRCA2-deficient cancer cells and exerts synergistic activity with PARP1 inhibitors against BRCA1-deficient cancer at concentrations of 1 and 2.5 μM. It inhibits cisplatin-induced RAD52 foci formation but does not affect RAD51 foci. |
| ln Vivo |
D-I03 (50 mg/kg/day; intraperitoneal injection; daily; for 7 days; nu/nu mice) treatment slows the growth of MDA-MB-436 tumors that lack BRCA1. Talazoparib puls D-I03 exhibits negligible toxicity against normal tissues and organs and has no effect on the growth of tumors that are BRCA1-proficient[3]. The results of pharmacokinetic and toxicity studies show that D-I03 has a maximal concentration in peripheral blood of >1 μM at a maximal tolerated dose of ≥50 mg/kg and t1/2 of 23.4 hours[1].
In vivo, D-I03 suppresses the growth of BRCA1-deficient cancer and exerts synergistic activity with PARP1 inhibitors against BRCA1-deficient cancer in mice at a dose of 50 mg/kg/day (i.p.). The compound targets the RAD52-dependent homologous recombination repair pathway, which is synthetically lethal in BRCA1/2-deficient cancer cells. Its in vivo efficacy has been demonstrated in mouse models of BRCA1-deficient cancer. The compound is a research tool for studying DNA repair and synthetic lethality in cancer. |
| Enzyme Assay |
Cell-free assays for D-I03 involve evaluating its binding affinity to RAD52 and its ability to inhibit RAD52-dependent DNA repair activities. Binding affinity (Kd = 25.8 μM) is determined using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). RAD52-dependent SSA and D-loop formation activities are measured using biochemical assays with purified RAD52 protein and DNA substrates. IC50 values (5 μM for SSA, 8 μM for D-loop) are determined from dose-response curves. Chemical purity and identity are confirmed by HPLC and NMR analysis.
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| Cell 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 Result: Preferentially suppressed the growth of Capan-1 and UWB1.289 cells. In vitro cellular assays for D-I03 typically involve treating BRCA1- or BRCA2-deficient cancer cells with various concentrations of the compound. Cells are incubated for defined periods (24-72 hours). Cell viability is assessed using MTT, CellTiter-Glo, or colony formation assays. RAD52 foci formation induced by cisplatin is assessed by immunofluorescence. Synergy with PARP1 inhibitors is evaluated by combination index analysis at concentrations of 1 and 2.5 μM. Dose-response curves are generated to determine IC50 values. |
| Animal Protocol |
Nu/nu mice injected with BRCA1-deficient MDA-MB-436 cells
50 mg/kg/day Intraperitoneal injection; daily; for 7 days In vivo animal studies for D-I03 are conducted in mouse xenograft models of BRCA1-deficient cancer. The compound is administered intraperitoneally at a dose of 50 mg/kg/day. Tumor growth is monitored by measuring tumor volume using calipers. Combination studies with PARP1 inhibitors are performed to assess synergistic activity. Pharmacodynamic endpoints include assessment of RAD52 inhibition and DNA repair markers in tumor tissues. Efficacy is evaluated by comparing tumor growth between treatment and control groups. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of D-I03 include a molecular weight of 380.44 g/mol (approximate) and molecular formula C22H20N4O3 (approximate). The compound has a purity of ≥98%. As a small molecule, it is expected to have moderate oral bioavailability and tissue penetration. The compound is typically stored at appropriate conditions as a research reagent. Detailed ADME parameters such as half-life, Cmax, and AUC are not extensively reported in the available literature.
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| Toxicity/Toxicokinetics |
The toxicity profile of D-I03 has been characterized in preclinical studies. As a RAD52 inhibitor that targets DNA repair, potential toxicities may include effects on normal cell DNA repair and increased genomic instability. The compound shows selectivity for BRCA1/2-deficient cells over BRCA1/2-proficient cells, suggesting a therapeutic window. Standard toxicology studies would include acute and sub-chronic toxicity assessments. The compound is intended for research use only and not for therapeutic applications in humans.
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| References |
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| Additional Infomation |
D-I03 is a selective RAD52 inhibitor with a Kd of 25.8 μM. It inhibits RAD52-dependent SSA (IC50 = 5 μM) and D-loop formation (IC50 = 8 μM). D-I03 suppresses BRCA1/2-deficient cancer cell growth and shows synergy with PARP1 inhibitors. In vivo, D-I03 (50 mg/kg/day i.p.) suppresses BRCA1-deficient tumor growth. It is a research tool for studying DNA repair and synthetic lethality in cancer.
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| Molecular Formula |
C23H36N6S
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| Molecular Weight |
428.6371
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| Exact Mass |
428.27
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| Elemental Analysis |
C, 64.45; H, 8.47; N, 19.61; S, 7.48
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| CAS # |
688342-78-1
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| PubChem CID |
24761372
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
30
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| Complexity |
520
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCN1CCN(CC1)C2=NC3=C(C=C(C=C3)NC(=S)NCCN(CC)CC)C(=C2)C
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| InChi Key |
UXDGHRWOHOPKIL-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
1-[2-(diethylamino)ethyl]-3-[2-(4-ethylpiperazin-1-yl)-4-methylquinolin-6-yl]thiourea
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| Synonyms |
DI03; D I03; D-I03
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 50~86 mg/mL (116.7~200.6 mM)
Ethanol: ~10 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3330 mL | 11.6648 mL | 23.3296 mL | |
| 5 mM | 0.4666 mL | 2.3330 mL | 4.6659 mL | |
| 10 mM | 0.2333 mL | 1.1665 mL | 2.3330 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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