| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 50mg | |||
| Other Sizes |
| Targets |
A12B4C3 targets human polynucleotide kinase/phosphatase (hPNKP), a DNA repair enzyme that plays a critical role in the repair of DNA strand breaks. PNKP has both kinase and phosphatase activities, which are required for the processing of DNA termini at single-strand and double-strand breaks. The kinase activity phosphorylates 5'-hydroxyl termini, while the phosphatase activity dephosphorylates 3'-phosphate termini, generating the 5'-phosphate and 3'-hydroxyl groups required for DNA ligation. A12B4C3 is a potent and selective inhibitor of hPNKP. By inhibiting PNKP, A12B4C3 disrupts the repair of DNA strand breaks, leading to the accumulation of DNA damage and enhanced cellular radiosensitivity.
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| ln Vitro |
The activity of hPNKP phosphatase is significantly inhibited by A12B4C3 (0-10 μM) [1]. A549 and MDA-MB-231 cell proliferation is reduced in a dose-dependent manner by A12B4C3 (0-100 μM; 72 hours) [1]. A12B4C3 (1 μM; 24 hours) raises A549 cells' radiosensitivity [1].
In vitro studies have demonstrated that A12B4C3 is a potent and selective inhibitor of hPNKP. It enhances cellular radiosensitivity, making cancer cells more susceptible to radiation-induced cell death. A12B4C3 has been used to study its effects on prostate cancer (PC-3) cells. By inhibiting PNKP, A12B4C3 disrupts DNA repair, leading to the accumulation of DNA damage and increased cell death. These in vitro findings establish A12B4C3 as a valuable tool for studying DNA repair mechanisms and for exploring potential strategies for radiosensitization in cancer therapy. |
| ln Vivo |
In vivo activity data for A12B4C3 is limited, as the compound is primarily used as a research tool in in vitro studies. However, its mechanism of action—inhibiting PNKP and enhancing radiosensitivity—suggests potential in vivo applications in combination with radiation therapy for cancer treatment. The compound could be used in animal models to study the effects of PNKP inhibition on tumor response to radiation. However, specific in vivo protocols and results, such as dosing regimens, routes of administration, and pharmacokinetic parameters, are not detailed in the available literature.
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| Enzyme Assay |
The in vitro assays for A12B4C3 measure its inhibition of hPNKP activity. PNKP activity is typically measured using phosphatase or kinase activity assays with specific substrates. The inhibition of enzyme activity is calculated, and the IC50 is determined. The compound's selectivity for PNKP over other phosphatases and kinases can be assessed by testing it against a panel of enzymes. These assays confirm that A12B4C3 is a potent and selective inhibitor of hPNKP.
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| Cell Assay |
Cell proliferation assay[1]
Cell Types: A549 and MDA-MB-231 (incubated with A12B4C3 for 2 hrs (hours), followed by irradiation with 0-10 Gy) Tested Concentrations: 1 μM Incubation Duration: 24 hrs (hours) Experimental Results: Radiosensitivity of A549 cells increased by almost 1 times. In vitro cell-based assays for A12B4C3 are used to study its effects on DNA repair and radiosensitivity. Cancer cells (e.g., PC-3 prostate cancer cells) are treated with A12B4C3, and the accumulation of DNA damage is assessed by measuring the levels of phosphorylated H2AX (γ-H2AX) foci, a marker of DNA double-strand breaks. Cell viability is assessed after radiation exposure to determine the compound's ability to enhance radiosensitivity. These cell-based assays confirm that A12B4C3 inhibits PNKP, disrupts DNA repair, and enhances cellular radiosensitivity. |
| Animal Protocol |
In vivo animal experiments for A12B4C3 are not extensively described in the available literature. As a research compound, its use in vivo would be determined by the specific research question being addressed. A typical protocol for studying a PNKP inhibitor like A12B4C3 would involve its administration to tumor-bearing mice in combination with radiation therapy. The compound would be formulated for injection, and tumor growth and response to radiation would be assessed. However, specific protocols for A12B4C3 are not detailed in the available literature.
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| ADME/Pharmacokinetics |
A12B4C3 has a molecular weight of 534.65 g/mol and a molecular formula of C30H38N4O5. It is a solid compound with a purity of 98.0%. For storage, it is recommended to keep the powder at -20°C for up to 3 years. In solvent, it can be stored at -80°C for 1 year. The compound is shipped with blue ice or at ambient temperature. Pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) have not been extensively characterized. A12B4C3 is a research compound and is not intended for human or veterinary use.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for A12B4C3 is not provided in standard product descriptions. As a research compound, its toxicity profile has not been extensively characterized. A12B4C3 is an inhibitor of PNKP, and its toxicity would be related to its effects on DNA repair in normal tissues. As with all research chemicals, standard laboratory safety precautions should be followed when handling A12B4C3. Its use is limited to research applications and it is not intended for human or veterinary use.
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| References | |
| Additional Infomation |
A12B4C3 is a research compound and is not approved for any clinical or therapeutic use. It is a potent and selective inhibitor of human polynucleotide kinase/phosphatase (hPNKP). A12B4C3 enhances cellular radiosensitivity. It has been used as an inhibitor of PNKP to study its effects on prostate cancer (PC-3) cells. A12B4C3 is used to study the role of PNKP in DNA repair and to explore potential strategies for radiosensitization in cancer therapy. Its mechanism of action involves inhibiting PNKP, disrupting the repair of DNA strand breaks, and enhancing the sensitivity of cancer cells to radiation.
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| Molecular Formula |
C30H38N4O5
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| Molecular Weight |
534.65
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| Exact Mass |
534.284
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| CAS # |
1005129-80-5
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| PubChem CID |
6610064
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
6.211
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
39
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| Complexity |
847
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KVHGJAKTBPFFNV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H38N4O5/c1-2-3-4-5-6-7-8-12-15-27(35)26-21-20-25-28(30(37)32(29(25)36)23-13-10-9-11-14-23)33(26)31-22-16-18-24(19-17-22)34(38)39/h9-11,13-14,16-21,25-28,31,35H,2-8,12,15H2,1H3
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| Chemical Name |
2-(1-hydroxyundecyl)-1-(4-nitroanilino)-6-phenyl-4a,7a-dihydro-2H-pyrrolo[3,4-b]pyridine-5,7-dione
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| Synonyms |
A12B4C3 A 12 B 4 C 3 A-12-B-4-C-3
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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 : ~53 mg/mL (~99.13 mM)
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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 | 1.8704 mL | 9.3519 mL | 18.7038 mL | |
| 5 mM | 0.3741 mL | 1.8704 mL | 3.7408 mL | |
| 10 mM | 0.1870 mL | 0.9352 mL | 1.8704 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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