GSK951
GSK951 is a highly potent, selective, and reversibly covalent KLK5 inhibitor, with an IC50 of approximately 250 pM and a pIC50 of 9.6 against hKLK5. It exhibits over 100-fold selectivity over KLK7, KLK14, matriptase, and elastase. GSK951 binds to the catalytic site of KLK5 via covalent interaction with the catalytic serine, with a slow dissociation rate. GSK951 improves skin barrier function, reduces transepidermal water loss, decreases the expression of proinflammatory cytokines, and inhibits the elevated KLK5 protease activity in the stratum corneum. GSK951 can be used in studies related to skin barrier dysfunction.
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- CAS No.: 2393881-77-9
- Formule: C22H19BF3N3O3
- Masse moléculaire:441.21
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
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KLK5 250 pM (IC50) |
KLK5 9.6 (pIC50) |
KLK7 4.1 (pIC50) |
KLK14 7.5 (pIC50) |
matriptase 5.9 (Kd) |
GSK951 potently and selectively inhibits human KLK5 with an IC50 of 250 pM. It forms key catalytic site interactions with KLK5 orthologs and exhibits over 100-fold selectivity against related skin serine proteases[1].
GSK951 (0.3% w/w cream formulation; 16 h) reaches a high average concentration of 471 μM in the epidermis of ex vivo healthy human skin after 16 hours[1].
GSK951 exhibits over 100-fold selectivity for KLK5 over KLK7, KLK14, matriptase, and elastase, with pIC50 values of 4.1, 7.5, 5.9, and <4, respectively, against these counter-targets[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Hemizygous transgenic human KLK5 (Tg-KLK5) mice[1]
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Dosage:0.3% w/w (KLK5 activity inhibition); 0.3% w/w (TEWL); 0.3% w/w (proinflammatory cytokine expression)
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Administration:topical; single dose; 3 hours (KLK5 activity inhibition); topical; twice daily; 3 days (TEWL); topical; twice daily; 21 days (proinflammatory cytokine expression)
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Result:Significantly reduced KLK5-dependent fluorescent signal in the stratum corneum relative to vehicle.
Reduced transepidermal water loss by approximately 50% within 24 hours of the first dose and maintained this reduction throughout the dosing period relative to vehicle.
Significantly reduced mRNA expression of proinflammatory mediators: IL-17A, IL-17F, S100A8, and S100A9 relative to vehicle.
Chemical Information
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CAS No. 2393881-77-9
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Masse moléculaire 441.21
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Formule C22H19BF3N3O3
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SMILES
OB1C2=CC(C(F)(F)F)=CC=C2C[C@@](C3=CC(OCC4=CN=CC=C4)=C(C=C3)C(N)=N)([H])O1
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GSK951 Related Classifications
HY-150085 Related Classifications
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