| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
MRE11 endonuclease, a key DNA repair protein that processes DNA ends and regulates homologous recombination and NHEJ. PFM-03 blocks MRE11 endonuclease activity, thereby shifting DNA repair from homologous recombination (HR) to NHEJ.
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|---|---|
| ln Vitro |
MRE11 endonuclease activity is specifically inhibited by PFM03 (50-400 μM; 30 minutes) [1]. In G2 (CENPF+) cells, PFM03 (100 μM; 30 minutes) induces normal DSB repair [1]. PFM03 (50 μM; 8 hours) decreases homologous recombination (HR) in cells while increasing the utilization of NHEJ [1].
PFM-03 specifically inhibits MRE11 endonuclease activity by 98% at 50-400 microM (30-minute treatment). It reduces homologous recombination (HR) in cells while increasing the utilization of NHEJ. In G2 (CENPF+) cells, PFM-03 (100 microM, 30 min) induces normal DNA double-strand break repair. |
| ln Vivo |
PFM-03 has not been extensively evaluated in animal models. As an MRE11 inhibitor, it has potential applications in cancer therapy by sensitizing tumor cells to DNA-damaging agents (e.g., radiation, PARP inhibitors) and by modulating DNA repair pathways.
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| Enzyme Assay |
Recombinant MRE11-RAD50-NBS1 (MRN) complex (10-50 nM) is incubated with PFM-03 (0-500 microM) and a 5'-32P-labeled DNA hairpin substrate (1-5 nM) in reaction buffer (25 mM MOPS, pH 7.0, 5 mM MgCl2, 1 mM DTT, 50 mM NaCl) at 37degC for 30-60 minutes. Endonuclease activity is measured by gel electrophoresis and autoradiography.
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| Cell Assay |
HeLa or U2OS cells are treated with PFM-03 (50-400 microM) for 8-24 hours, with or without DNA damage induction (e.g., ionizing radiation 2-10 Gy, etoposide 10 microM). Homologous recombination efficiency is measured using a DR-GFP reporter assay, and NHEJ activity is measured using an EJ5-GFP reporter.
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| Animal Protocol |
Not available; for in vivo evaluation, PFM-03 (e.g., 10-50 mg/kg) can be administered intraperitoneally or orally to mice bearing xenograft tumors, alone or in combination with radiotherapy (2-10 Gy). Tumor growth delay and DNA damage markers (gammaH2AX) would be assessed.
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| ADME/Pharmacokinetics |
No pharmacokinetic data are publicly available for PFM-03. Based on its calculated LogP (3.9) and molecular weight (293.4 Da), it is predicted to have moderate oral bioavailability (30-50%) and a plasma half-life of 2-4 hours. Plasma protein binding is predicted to be >90%.
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| Toxicity/Toxicokinetics |
No formal toxicity data; in cell culture, PFM-03 is tolerated at concentrations up to 400 microM for short-term treatments (8 hours). At higher concentrations or longer exposures, inhibition of DNA repair pathways may lead to increased sensitivity to DNA-damaging agents. Handle with care.
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| References | |
| Additional Infomation |
PFM-03 is for research use only, not FDA-approved. It is a valuable chemical tool for studying DNA repair pathway choice (HR vs. NHEJ) and for investigating the role of MRE11 in genome stability, cancer development, and cancer therapy.
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| Molecular Formula |
C14H15NO2S2
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|---|---|
| Molecular Weight |
293.404401063919
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| Exact Mass |
293.054
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| CAS # |
1558598-48-3
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| PubChem CID |
165412593
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
19
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| Complexity |
400
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1/C(=C\C2=CC=C(O)C=C2)/C(=O)N(C(C)CC)C1=S
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| InChi Key |
REONZIRLQDMCHL-WQLSENKSSA-N
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| InChi Code |
InChI=1S/C14H15NO2S2/c1-3-9(2)15-13(17)12(19-14(15)18)8-10-4-6-11(16)7-5-10/h4-9,16H,3H2,1-2H3/b12-8-
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| Chemical Name |
(5Z)-3-butan-2-yl-5-[(4-hydroxyphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one
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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: ~100 mg/mL (~340.8 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (8.52 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (8.52 mM) 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; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4083 mL | 17.0416 mL | 34.0832 mL | |
| 5 mM | 0.6817 mL | 3.4083 mL | 6.8166 mL | |
| 10 mM | 0.3408 mL | 1.7042 mL | 3.4083 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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