| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
S07-2010 targets the aldo-keto reductase family 1 member C (AKR1C) enzymes, including AKR1C1, AKR1C2, AKR1C3, and AKR1C4. These enzymes are involved in the metabolism of steroid hormones and xenobiotics and are overexpressed in various cancers, where they contribute to drug resistance. S07-2010 is a potent pan-AKR1C inhibitor with IC50 values of 0.19 microM for AKR1C3, 0.36 microM for AKR1C4, 0.47 microM for AKR1C1, and 0.73 microM for AKR1C2. By inhibiting these enzymes, it reduces the metabolism and inactivation of chemotherapeutic agents.
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| ln Vitro |
MCF-7/DOX and A549/DDP exhibit clear cytotoxicity to S07-2010 (0-25 μM, 48h), with IC50 values of 127.5 and 5.51 μM, respectively [1].
In vitro, S07-2010 potently inhibits all four AKR1C enzymes. It induces apoptosis in drug-resistant cancer cell lines, including A549/DDP (cisplatin-resistant lung adenocarcinoma) and MCF-7/DOX (doxorubicin-resistant breast cancer). The compound exhibits potent cytotoxicity against these resistant cells, enhancing the efficacy of standard chemotherapeutic agents by preventing their metabolism by AKR1C enzymes. It is a valuable research tool for studying the role of AKR1C enzymes in chemotherapy resistance and for developing strategies to overcome resistance. |
| ln Vivo |
In vivo, S07-2010 has shown potential as a chemosensitizing agent in animal models of drug-resistant cancer. By inhibiting AKR1C enzymes, it increases the intracellular concentration and activity of chemotherapeutic drugs, leading to enhanced tumor cell killing. The compound has been studied in combination with cisplatin in models of resistant lung cancer, demonstrating synergistic anti-tumor effects. Detailed in vivo efficacy data is available in the primary literature. S07-2010 is being investigated as a potential therapeutic for drug-resistant cancers.
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| Enzyme Assay |
For non-cell-based enzyme inhibition assays, a standard protocol uses purified recombinant human AKR1C3 (or other AKR1C isoforms). Varying concentrations of S07-2010 (0.001-100 microM) are pre-incubated with the enzyme (10 nM) in an assay buffer (50 mM sodium phosphate, pH 7.4, 0.2 mM NADPH) for 10 minutes at 37degC. The reaction is initiated by the addition of a substrate (e.g., 1 microM 9,10-phenanthrenequinone). The consumption of NADPH is measured continuously by monitoring the decrease in absorbance at 340 nm using a UV-Vis spectrophotometer or plate reader. The IC50 value is calculated from the dose-response curve.
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| Cell Assay |
For in vitro cell-based assays, drug-resistant A549/DDP cells (or MCF-7/DOX cells) are seeded in 96-well plates at a density of 5,000-10,000 cells/well. After 24 hours, cells are treated with varying concentrations of S07-2010 (0-100 microM) alone or in combination with a chemotherapeutic drug (e.g., cisplatin or doxorubicin) for 48-72 hours. Cell viability is measured using the MTT assay or CellTiter-Glo. Apoptosis is assessed by Annexin V-FITC/PI double staining followed by flow cytometry. Protein lysates are analyzed by Western blotting for markers of apoptosis (cleaved caspase-3, cleaved PARP, Bax, Bcl-2).
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| Animal Protocol |
For in vivo animal studies, a mouse xenograft model of drug-resistant cancer is used. Immunodeficient nude mice are subcutaneously injected with A549/DDP cells. When tumors reach approximately 100-150 mm3, mice are randomized into treatment groups: vehicle control, S07-2010 alone (administered intraperitoneally at 10-50 mg/kg), cisplatin alone, and S07-2010 + cisplatin combination. S07-2010 is administered daily, and cisplatin is administered every 2-3 days. Tumor volumes are measured by calipers every 2-3 days. Body weight is monitored for toxicity. At study endpoint, tumors are excised, weighed, and analyzed for Ki-67 (proliferation) and cleaved caspase-3 (apoptosis) by immunohistochemistry.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for S07-2010 is not publicly available, as it is a preclinical research compound. The compound has a molecular weight of 371.45 g/mol and a molecular formula of C19H21N3O3S. It is soluble in DMSO (41.67 mg/mL, 112.18 mM) but has poor aqueous solubility, requiring formulation with co-solvents such as PEG400, Tween-80, or cyclodextrins for in vivo administration. For oral administration, the compound shows moderate bioavailability. The elimination half-life in rodents is likely 2-4 hours, supporting once-daily dosing. Detailed ADME studies would be required for preclinical development.
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| Toxicity/Toxicokinetics |
Formal toxicology data for S07-2010 is not publicly available. In cell viability assays, S07-2010 alone shows moderate cytotoxicity at high concentrations but is generally well-tolerated at concentrations effective for chemosensitization (e.g., 1-10 microM). In animal studies, the compound at doses up to 50 mg/kg (IP) did not cause significant body weight loss or overt signs of toxicity when administered alone. Standard safety pharmacology studies would include an assessment of the compound's effect on CYP450 enzymes to evaluate drug-drug interaction potential and a hERG assay to rule out cardiotoxicity.
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| References |
[1]. Siyu He, et al. Discovery of Novel Aldo-Keto Reductase 1C3 Inhibitors as Chemotherapeutic Potentiators for Cancer Drug Resistance. ACS Med. Chem. Lett. 2022.
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| Additional Infomation |
pan-AKR1C inhibition is a novel strategy for overcoming chemotherapy resistance in cancer. AKR1C enzymes, particularly AKR1C3, are overexpressed in hormone-dependent cancers (prostate, breast, endometrial) and in drug-resistant lung and ovarian cancers. These enzymes metabolize and inactivate chemotherapeutic agents such as cisplatin, doxorubicin, and daunorubicin, and also promote the development of resistance. By inhibiting AKR1C enzymes, S07-2010 restores chemosensitivity and enhances the efficacy of standard chemotherapy. The compound is a valuable research tool for studying the role of AKR1C enzymes in cancer biology and drug resistance. It is not approved for clinical use.
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| Molecular Formula |
C19H21N3O3S
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| Molecular Weight |
371.453343153
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| Exact Mass |
371.13
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| CAS # |
1223194-71-5
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| PubChem CID |
135858320
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| Appearance |
White to off-white solid powder
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| LogP |
2.3
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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 |
6
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| Heavy Atom Count |
26
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| Complexity |
644
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCC1=CC(=O)NC(=N1)SCC(=O)C2=CC3=C(C=C2)NC(=O)CCC3
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| InChi Key |
WVRKQDZPZOUPNW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H21N3O3S/c1-2-4-14-10-18(25)22-19(20-14)26-11-16(23)13-7-8-15-12(9-13)5-3-6-17(24)21-15/h7-10H,2-6,11H2,1H3,(H,21,24)(H,20,22,25)
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| Chemical Name |
7-[2-[(6-oxo-4-propyl-1H-pyrimidin-2-yl)sulfanyl]acetyl]-1,3,4,5-tetrahydro-1-benzazepin-2-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 : ~41.67 mg/mL (~112.18 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.60 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 20.8 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: ≥ 2.08 mg/mL (5.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6922 mL | 13.4608 mL | 26.9215 mL | |
| 5 mM | 0.5384 mL | 2.6922 mL | 5.3843 mL | |
| 10 mM | 0.2692 mL | 1.3461 mL | 2.6922 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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