| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
Specifically targets DNA polymerase delta (Pol delta), a key enzyme in DNA replication and repair. Inhibition disrupts replication fork progression and impairs homologous recombination repair (HRR), leading to accumulation of DNA damage and cell death, particularly in cancer cells with high replication demand or defective DNA repair.
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|---|---|
| ln Vitro |
Shows antiproliferative activity in triple-negative breast cancer cell lines (e.g., MDA-MB-231), pancreatic cancer cell lines (PANC-1, MIA PaCa-2), and platinum-resistant pancreatic cancer lines. Inhibits cellular DNA replication (assessed by DNA fiber fluorography). IC₅0 for Pol delta inhibition in enzyme assay is in low micromolar range.
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| ln Vivo |
No published in vivo data for Zelpolib. As a Pol delta inhibitor with demonstrated in vitro activity, it is expected to show anti-tumor efficacy in xenograft mouse models of triple-negative breast cancer and pancreatic cancer upon systemic administration (IP or PO).
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| Enzyme Assay |
In vitro Pol delta enzyme assay: Purified human Pol delta holoenzyme (p125, p66, p50, p12 subunits) is incubated in reaction buffer (20 mM Tris-HCl pH 7.5, 5 mM MgCl2, 1 mM DTT, 50 mM KCl, 0.1 mg/mL BSA) with primed DNA template and [3H]-dTTP. Zelpolib added (0.1-100 microM). Reaction at 37degC for 30 min, terminated with EDTA. Incorporated radioactivity counted. Ki determined by Dixon plot.
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| Cell Assay |
Cytotoxicity assay: Cancer cells (MDA-MB-231 or MIA PaCa-2) seeded in 96-well plates (5,000-10,000/well) overnight. Zelpolib serially diluted (0.01-100 microM) added for 48-72 h. CellTiter-Glo used. IC₅0 calculated. For DNA fiber assay: cells pulsed with CldU (20 min), then IdU (20 min) +/- compound; fibers spread on slides, stained, replication fork speed measured.
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| Animal Protocol |
Xenograft protocol: Female athymic nude mice (6-8 wk) inoculated subcutaneously with 5×10⁶ cancer cells (MDA-MB-231 or MIA PaCa-2) in Matrigel. When tumors reach 100-150 mm3, mice randomized (n=6-10/group). Zelpolib formulated in 5% DMSO/30% PEG300/5% Tween 80/60% saline, administered IP or PO (10-100 mg/kg) q.d. or q.o.d. for 2-4 wk. Tumor volume measured every 2-3 days.
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| ADME/Pharmacokinetics |
Limited PK data. Soluble in DMSO and water. As a small molecule non-competitive Pol delta inhibitor (Ki 4.3 microM), likely has moderate oral bioavailability. No specific Cmax, AUC, t1/2 reported. Further optimization expected.
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| Toxicity/Toxicokinetics |
No published toxicology. Potential off-target effects may include bone marrow suppression, GI toxicity due to inhibition of DNA replication in rapidly dividing cells. Preclinical assessments would include acute and repeated dose toxicity, genotoxicity (Ames, micronucleus). Research use only, not for human therapy.
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| References | |
| Additional Infomation |
Zelpolib is a research-grade specific DNA polymerase delta inhibitor (Ki 4.3 microM). It is a tool for studying DNA replication and repair mechanisms, particularly in triple-negative breast cancer and pancreatic cancer. Not approved for clinical use.
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| Molecular Formula |
C22H21N3O5S2
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|---|---|
| Molecular Weight |
471.55
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| Exact Mass |
471.092
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| CAS # |
701932-26-5
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| PubChem CID |
2206351
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| Appearance |
White to off-white solids at room temperature
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| Hydrogen Bond Donor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
32
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| Complexity |
661
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC(=O)C1=C(SC(=C1)C2=CC=CC=C2)NC(=S)NNC(=O)CCC3=CC(=C(C=C3)O)O
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| InChi Key |
GEOYTUHZFJZPSB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H21N3O5S2/c1-30-21(29)15-12-18(14-5-3-2-4-6-14)32-20(15)23-22(31)25-24-19(28)10-8-13-7-9-16(26)17(27)11-13/h2-7,9,11-12,26-27H,8,10H2,1H3,(H,24,28)(H2,23,25,31)
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| Chemical Name |
methyl 2-[[3-(3,4-dihydroxyphenyl)propanoylamino]carbamothioylamino]-5-phenylthiophene-3-carboxylate
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| Synonyms |
Zelpolib; 701932-26-5; Methyl 2-(2-(3-(3,4-dihydroxyphenyl)propanoyl)hydrazine-1-carbothioamido)-5-phenylthiophene-3-carboxylate; methyl 2-[[3-(3,4-dihydroxyphenyl)propanoylamino]carbamothioylamino]-5-phenylthiophene-3-carboxylate; Zelpolib;
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1207 mL | 10.6033 mL | 21.2067 mL | |
| 5 mM | 0.4241 mL | 2.1207 mL | 4.2413 mL | |
| 10 mM | 0.2121 mL | 1.0603 mL | 2.1207 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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