SG-55
SG-55 is a selective, noncompetitive and orally active AKR1C3 inhibitor with an IC50 of 5 nM and a Ki of 10 nM. SG-55 shows >2000-fold selectivity for AKR1C3 over AKR1C1, AKR1C2, and AKR1C4 (> 10 μM). SG-55 increases the ratio of reduced/oxidized nicotinamide adenine dinucleotide phosphate (NADPH/NADP+), decreases the ratio of reduced/oxidized glutathione (GSH/GSSG), and induces DNA double-strand breaks. SG-55 can overcome Osimertinib (HY-15772) resistance mediated by EGFR C797S triple mutation in non-small cell lung cancer (NSCLC).
For research use only. We do not sell to patients.
- Formula: C19H17N3O2
- Molecular Weight:319.36
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
AKR1C3 5 nM (IC50) |
AKR1C3 10 nM (IC50) |
In Vitro
SG-55 (0.5-100 μM; 72 h) does not inhibits the cell growth of AKR1C3-overexpressing PC-9/OR cell line (PC-9 EGFR 19Del/T790M/C797S cells)[1].
SG-55 (72 h) at 10 μM, 20 μM and 50 μM decreased the IC50 of Osimertinib (100-500 nM) in PC-9/OR cells from 2.59 μM to 1.30 μM, 0.43 μM and 0.23 μM, respectively, corresponding to resistance-reversal factors of 2, 6 and 11-fold[1].
SG-55 (10 μM) cooperates with Osimertinib to suppress clonogenicity (14 days), curtail migration (24 h), and amplify cycle arrest (24 h) and apoptosis (72 h), thereby conferring significant sensitization in PC-9/OR cells[1].
SG-55 (10 μM; 72 h)-mediated AKR1C3 inhibition elevates the NADPH/NADP+ ratio, disrupts the GSH cycle, breaks redox balance, and amplifies oxidative damage, thereby overcoming EGFR mutation-driven Osimertinib resistance in PC-9/OR cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:AKR1C3-overexpressing PC-9/OR cell lines
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Concentration:10 μM plus Osimertinib (100 nM)
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Incubation Time:72 h
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Result:AKR1C3 Inhibition enhanced Osimertinib-induced apoptosis.
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Cell Line:AKR1C3-overexpressing PC-9/OR cell lines
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Concentration:10 μM plus Osimertinib (100 nM)
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Incubation Time:24 h
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Result:Osimertinib alone imposed a G0/G1 arrest, whereas the addition of the compound shifted the cycle distribution to G2/M accumulation.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male BALB/c nude mice (6 weeks old) were inoculated subcutaneously in the right flank with 3 × 107 PC-9/OR cells (100 μL) to establish xenografts[1].
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Dosage:10 mg/kg plus Osimertinib (5 mg/kg p.o.)
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Administration:p.o.; every 1 days; for 21 days
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Result:The tumor-growth inhibition (TGI) values of 15.6%.
When used in combination with osimertinib, the TGI was 93.1%.
No significant body-weight loss was observe.
Chemical Information
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Molecular Weight 319.36
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Formula C19H17N3O2
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SMILES
N#CC1=CC2=C(C=C1)CN(C(C3=CC(C(C4CC4)=O)=CN3)=O)CC2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Genotoxicity/Mutagenicity Study
The bacterial reverse mutation assay detects point mutations that restore amino-acid prototrophy in auxotrophic Salmonella typhimurium or Escherichia coli tester strains; after exposure to a test article, mutagenic activity is read out as an increased number of revertant colonies on minimal agar compared with the vehicle control. The assay uses tester strains with different mutation targets so that base-substitution and frameshift mutagens can be detected, and testing is performed with and without exogenous mammalian metabolic activation because some chemicals require biotransformation to become mutagenic.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SG-55 Related Classifications
HY-181542 Related Classifications
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