KR-67607
KR-67607 is a selective 11β-HSD1 inhibitor, with an IC50 value of 4.8 nM against h11β-HSD1 and 7.1 nM against mouse 11β-HSD1. KR-67607 inhibits stress-induced Glucocorticoid receptor nuclear translocation, reduces cortisol levels, suppresses the expression of ROS and proinflammatory cytokines, and enhances Nrf-2-mediated antioxidant gene transcription. KR-67607 maintains trabecular meshwork structure and reverses elevated intraocular pressure. KR-67607 improves ocular antioxidant activity and mucus secretion, reverses ocular surface damage, and prevents ischemia-reperfusion induced ocular injury. KR-67607 can be used in research related to glaucoma and dry eye disease.
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- No. CAS: 1401564-00-8
- Fòrmula: C24H29Cl2F3N4O4S
- Peso molecular:597.48
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Almacenamiento:
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Actividad biológica
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Chemical Information
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- Referencias
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Help & FAQs
Actividad biológica
IC50: 4.8 nM against h11β-HSD1 and 7.1 nM against mouse 11β-HSD1[1]
KR-67607 (3 h) potently and selectively inhibits the reductase activity of 11β-HSD1, with an IC50 value of 4.8 nM against h11β-HSD1 and 7.1 nM against mouse 11β-HSD1[1].
KR-67607 (0.001-2 μM; 1 h ischemia, 24 h reperfusion) potently inhibits 11β-HSD1 reductase activity in IAA-treated HTMC, with an inhibition rate >50% at 1 nM and >90% at concentrations ≥0.02 μM[1].
KR-67607 (0.001-2 μM; 1 h ischemia, 24 h reperfusion) dose-dependently increases the survival rate of IAA-treated HTMCs after ischemia-reperfusion injury[1].
KR-67607 (0.001-2 μM; 1 h ischemia, 24 h reperfusion) reduces IAA-treated HTMCs' LDH leakage in a dose-dependent manner, indicating its protective effect against ischemia-reperfusion induced cell membrane damage[1].
KR-67607 (1 h of ischemia followed by 7 h of reperfusion) attenuates apoptosis and inflammatory signaling in IAA-treated HTMCs after ischemia-reperfusion injury by regulating the protein expression of 11β-HSD1, BAX, Bcl-2, NF-κB and TNFα[1].
KR-67607 (at 24 h of reperfusion) protects HTMCs from ischemia-reperfusion-induced cell death by inhibiting 11β-HSD1, which is confirmed by the absence of a protective effect in 11β-HSD1-knockdown cells[1].
KR-67607 (1 h of ischemia followed by 24 h of reperfusion) protects HTMCs against IAA-induced F-actin disruption and restores normal F-actin structure and levels after ischemia-reperfusion injury[1].
KR-67607 (following 30 min of DCFH-DA incubation, the reperfusion duration can reach up to 180 min) significantly reduces intracellular ROS production in IAA-treated HTMC cells during ischemia-reperfusion injury[1].
KR-67607 (2-5 μM; 2 h reperfusion) dose-dependently increases the expression of HO-1 protein in IAA-treated HTMCs after ischemia-reperfusion injury, with no effect on the activation of p38 MAPK[1].
KR-67607 (2-5 μM) upregulates the expression of Nrf-2-ARE-related antioxidant genes (HO-1, NQO-1, GCLC) in IAA-treated HTMC after ischemia-reperfusion injury[1].
KR-67607 (2-5 μM; 2 h reperfusion) dose-dependently inhibits the nuclear translocation of GR induced by IAA in HTMC after ischemia-reperfusion injury[1].
KR-67607 potently and selectively inhibits the reductase activities of h11β-HSD1 and mouse 11β-HSD1 in CHO-K1 cells, with corresponding IC50 values of 4 nM and 7 nM, respectively, while exerting no significant inhibitory effect on related steroid dehydrogenases[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Primary human trabecular meshwork cells (HTMCs) under chemically induced ischemia-reperfusion
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Concentration:0.001-2 μM
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Incubation Time:1 h (ischemia); 24 h (reperfusion)
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Result:Effectively inhibited IAA-induced HTMC death in a dose-dependent manner, significantly increasing cell viability compared to untreated IAA-exposed cells.
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Cell Line:Primary human trabecular meshwork cells (HTMCs) under chemically induced ischemia-reperfusion
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Concentration:2-5 μM
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Incubation Time:2 h (reperfusion)
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Result:Resulted in dose-dependent increases in HO-1 protein levels compared to untreated IAA-exposed HTMCs, with significant increases observed at 5 μM.
Had no effect on phosphorylated or total p38 MAPK levels.
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Cell Line:Primary human trabecular meshwork cells (HTMCs) under chemically induced ischemia-reperfusion
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Concentration:2-5 μM
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Incubation Time:2 h (reperfusion)
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Result:Dose-dependently reduced IAA-induced nuclear translocation of GR, with significant reductions observed at 5 μM, as shown by both immunofluorescence imaging and quantitative analysis of nuclear GR protein levels.
KR-67607 (0.15-1.5 mg/mL; topical; twice daily; 4 days) dose-dependently reduces elevated IOP in a rat EVL model of glaucoma[1].
KR-67607 (0.75-1.5 mg/mL; topical; twice daily; 4 months) reduces IOP by up to 26.1% and prevents glaucomatous optic neuropathy in DBA/2 mice by attenuating RGC loss, suppressing astrocyte activation, and restoring ocular tissue structure[2].
KR-67607 (0.75-1.5 mg/mL; topical; twice daily; 10 days) prevents BAC-induced dry eye syndrome in SD rats by reducing ocular surface damage, restoring corneal epithelial thickness and basement membrane structure, suppressing oxidative stress and pro-inflammatory cytokine expression, improving mucus secretion, and reducing 11β-HSD1 expression[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (9-10-week-old males)[1]
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Dosage:20 mg/mL; 1.5 mg/mL
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Administration:topical; twice daily; 3 pre-treatment days plus 4 reperfusion days
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Result:Significantly reduced cortisol production in ischemic-reperfused eyes relative to untreated ischemic controls.
Maintained trabecular meshwork (TM) structure and Schlemm’s canal (SC) morphology, preventing the TM collapse observed in untreated ischemic eyes.
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Animal Model:Sprague-Dawley (SD) (7-8-week-old males)[1]
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Dosage:0.15 mg/mL; 0.75 mg/mL; 1.5 mg/mL
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Administration:topical; twice daily; 4 days
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Result:Significantly reduced elevated IOP relative to vehicle-treated controls on Day 4 post-EVL.
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Animal Model:DBA/2 mice (n=15 per treatment group; spontaneous glaucoma model, develops elevated intraocular pressure and glaucomatous optic neuropathy with age)[2]
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Dosage:0.75 mg/mL; 1.5 mg/mL
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Administration:topical; twice daily; 4 months
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Result:Reduced elevated IOP in DBA/2 mice by 16.7% with 0.75 mg/mL and by 26.1% with 1.5 mg/mL.
Restored normal thickness of the retinal nerve fiber layer (RNFL) and structure of the optic nerve head (ONH) in DBA/2 mice.
Decreased increased apoptotic cells (identified via cleaved Caspase-3, -9, and TUNEL staining) in KR-67607-treated DBA/2 mice.
Recovered retinal ganglion cell (RGC) loss caused by elevated IOP, confirmed by Brn3a immunostaining.
Eliminated intense GFAP localization at the ONH (a marker of glaucomatous injury) in KR-67607-treated DBA/2 mice.
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Animal Model:Sprague-Dawley (SD) (specific pathogen-free; dry eye syndrome induced by 0.2% benzalkonium chloride topical administration)[3]
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Dosage:0.75 mg/mL; 1.5 mg/mL
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Administration:topical; twice daily; 10 days
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Result:Reduced BAC-induced rose bengal staining scores in a concentration-dependent manner, with scores significantly lower than the BAC-only group (P < 0.05 for 0.75 mg/mL, P < 0.001 for 1.5 mg/mL).
Reversed BAC-induced reduction in corneal epithelial thickness, with significant increases observed for both 0.75 mg/mL (P < 0.05) and 1.5 mg/mL (P < 0.001) doses compared to the BAC-only group.
Restored BAC-induced basement membrane damage, with clearer, more intact staining observed in both dose groups.
Significantly suppressed BAC-induced increased expression of 4-hydroxynonenal (4-HNE) in conjunctival epithelial cells.
Reversed BAC-induced decreased expression of superoxide dismutase 1 (SOD1).
Suppressed BAC-induced increased expression of tumor necrosis factor-α (TNF-α) in conjunctival epithelial cells.
Improved BAC-reduced mucus secretion in conjunctival goblet cells.
Decreased BAC-induced increased expression of 11β-HSD1 in conjunctival epithelial cells.
Showed no ocular surface damage when administered alone, matching the control group.
Exhibited corneal epithelial thickness and basement membrane staining similar to controls when administered alone.
Chemical Information
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No. CAS 1401564-00-8
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Peso molecular 597.48
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Fòrmula C24H29Cl2F3N4O4S
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SMILES
NC(C12C[C@]3([H])[C@H]([C@](CC(C3)C2)([H])C1)NC(CN4S(=O)(N(C5=C(C=C(C=C5Cl)C(F)(F)F)Cl)CC(C4)C)=O)=O)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Choi KJ, et al. Protective effect of a novel selective 11β-HSD1 inhibitor on eye ischemia-reperfusion induced glaucoma. Biochem Pharmacol. 2019;169:113632. [Content Brief]
[3]. Na YJ, et al. A Novel Selective 11β-HSD1 Inhibitor, (E)-4-(2-(6-(2,6-Dichloro-4-(Trifluoromethyl)Phenyl)-4-Methyl-1,1-Dioxido-1,2,6-Thiadiazinan-2-yl)Acetamido)Adamantan-1-Carboxamide (KR-67607), Prevents BAC-Induced Dry Eye Syndrome. Int J Mol Sci. 2020;21(10):3729. [Content Brief]
Calculators
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