| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
POLA1 inhibitor 1 selectively targets POLA1, the catalytic subunit of DNA polymerase alpha-primase complex. POLA1 is essential for DNA replication initiation and elongation. Inhibiting POLA1 disrupts DNA replication in cancer cells, particularly those with high rates of DNA replication and repair.
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| ln Vitro |
POLA1 inhibitor 1 inhibits POLA1 enzymatic activity, leading to disruption of DNA replication and induction of replication stress. It exhibits antitumor activity against several tumor tissue types, including HT-29 and MM487 xenograft models. The compound also shows efficacy against Adarotene-resistant cell lines.
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| ln Vivo |
In HT-29 and MM487 xenografts, POLA1 inhibitor 1 (compound 12) (15 mg/kg and 50 mg/kg) had notable anticancer activity [1].
In HT-29 and MM487 xenograft models, POLA1 inhibitor 1 (15 mg/kg and 50 mg/kg) shows notable anticancer activity. As an orally bioactive compound, it is suitable for oral administration in animal studies, supporting its potential as an oral antitumor agent in preclinical research. |
| Enzyme Assay |
The inhibitory activity against POLA1 is measured using an in vitro polymerase assay. Recombinant POLA1 enzyme is incubated with a DNA template/primer and radiolabeled dNTPs. The incorporation of radioactive nucleotides into newly synthesized DNA is quantified, and the IC50 is calculated from the inhibition curve.
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| Cell Assay |
Cancer cell lines (e.g., HT-29 colon cancer, MM487 melanoma, and Adarotene-resistant lines) are cultured and treated with POLA1 inhibitor 1. Cell viability is assessed after 48-72 hours using MTT or CellTiter-Glo assays. The effect on DNA replication can be assessed by measuring BrdU incorporation.
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| Animal Protocol |
Subcutaneous xenograft tumor models are established in immunodeficient mice. POLA1 inhibitor 1 is administered orally at doses of 15 mg/kg and 50 mg/kg. Tumor volumes are measured regularly. Tumors are harvested for histopathological analysis and assessment of proliferation markers (e.g., Ki-67).
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| ADME/Pharmacokinetics |
Detailed PK parameters for POLA1 inhibitor 1 are not extensively documented. As an orally bioactive compound, it is absorbed after oral administration. Solubility data show it is soluble in DMSO at 180 mg/mL, and in vivo formulations using DMSO/PEG300/Tween80/saline are feasible.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for POLA1 inhibitor 1 are not extensively documented. As a research compound targeting DNA replication, potential toxicities may include effects on rapidly dividing normal tissues (bone marrow, gastrointestinal tract). Comprehensive toxicity studies are not publicly reported.
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| References |
[1]. Cincinelli R, et al. Novel adamantyl retinoid-related molecules with POLA1 inhibitory activity. Bioorg Chem. 2020 Nov;104:104253.
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| Additional Infomation |
POLA1 inhibitor 1 is a novel adamantyl retinoid-related molecule with POLA1 inhibitory activity. It is a research tool for studying DNA replication in cancer and for developing therapies targeting POLA1. The compound is not an approved clinical drug.
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| Molecular Formula |
C26H27NO4
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|---|---|
| Molecular Weight |
417.50
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| Exact Mass |
417.194
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| CAS # |
2217671-41-3
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| PubChem CID |
164517069
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| Appearance |
White to off-white solid powder
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| LogP |
6.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
690
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1C2CC3CC1CC(C2)(C3)C4=C(C=CC(=C4)C5=C(C=C(C=C5)/C=C/C(=O)O)/C=N/O)O
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| InChi Key |
PLQNJDDLZLIMNK-DTHWQZMASA-N
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| InChi Code |
InChI=1S/C26H27NO4/c28-24-5-3-20(22-4-1-16(2-6-25(29)30)10-21(22)15-27-31)11-23(24)26-12-17-7-18(13-26)9-19(8-17)14-26/h1-6,10-11,15,17-19,28,31H,7-9,12-14H2,(H,29,30)/b6-2+,27-15+
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| Chemical Name |
(E)-3-[4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-[(E)-hydroxyiminomethyl]phenyl]prop-2-enoic acid
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ~180 mg/mL (~431.14 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.5 mg/mL (10.78 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 45.0 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: ≥ 4.5 mg/mL (10.78 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 45.0 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: ≥ 4.5 mg/mL (10.78 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 | 2.3952 mL | 11.9760 mL | 23.9521 mL | |
| 5 mM | 0.4790 mL | 2.3952 mL | 4.7904 mL | |
| 10 mM | 0.2395 mL | 1.1976 mL | 2.3952 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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