Cat. No.: HY-183905

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.

For research use only. We do not sell to patients.

CAS No.: 1401564-00-8
Formula: C₂₄H₂₉Cl₂F₃N₄O₄S
Molecular Weight:597.48

Storage:

Please store the product under the recommended conditions in the Certificate of Analysis.

KR-67607 Chemical Structure

CAS No.: 1401564-00-8

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Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Purity & Documentation
References
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Biological Activity

Description

IC₅₀ & Target

IC₅₀: 4.8 nM against h11β-HSD1 and 7.1 nM against mouse 11β-HSD1^[1]

In Vitro

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.

Cell Viability Assay^[1]

Cell Line:

Primary human trabecular meshwork cells (HTMCs) under chemically induced ischemia-reperfusion
Concentration:

0.001-2 μM
Incubation Time:

1 h (ischemia); 24 h (reperfusion)
Result:

Effectively inhibited IAA-induced HTMC death in a dose-dependent manner, significantly increasing cell viability compared to untreated IAA-exposed cells.

Western Blot Analysis^[1]

Cell Line:

Primary human trabecular meshwork cells (HTMCs) under chemically induced ischemia-reperfusion
Concentration:

2-5 μM
Incubation Time:

2 h (reperfusion)
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.

Immunofluorescence^[1]

Cell Line:

Primary human trabecular meshwork cells (HTMCs) under chemically induced ischemia-reperfusion
Concentration:

2-5 μM
Incubation Time:

2 h (reperfusion)
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.

In Vivo

KR-67607 (1.5-20 mg/mL; topical; twice daily; 3 pre-treatment days plus 4 reperfusion days) effectively reduces cortisol levels in mouse eyes subjected to ischemia-reperfusion and preserves TM and SC structure, protecting against glaucoma-related tissue damage^[1].
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.

Animal Model:

C57BL/6 (9-10-week-old males)^[1]
Dosage:

20 mg/mL; 1.5 mg/mL
Administration:

topical; twice daily; 3 pre-treatment days plus 4 reperfusion days
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.

Animal Model:

Sprague-Dawley (SD) (7-8-week-old males)^[1]
Dosage:

0.15 mg/mL; 0.75 mg/mL; 1.5 mg/mL
Administration:

topical; twice daily; 4 days
Result:

Significantly reduced elevated IOP relative to vehicle-treated controls on Day 4 post-EVL.

Animal Model:

DBA/2 mice (n=15 per treatment group; spontaneous glaucoma model, develops elevated intraocular pressure and glaucomatous optic neuropathy with age)^[2]
Dosage:

0.75 mg/mL; 1.5 mg/mL
Administration:

topical; twice daily; 4 months
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.

Animal Model:

Sprague-Dawley (SD) (specific pathogen-free; dry eye syndrome induced by 0.2% benzalkonium chloride topical administration)^[3]
Dosage:

0.75 mg/mL; 1.5 mg/mL
Administration:

topical; twice daily; 10 days
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

CAS No. 1401564-00-8
Molecular Weight 597.48
Formula C₂₄H₂₉Cl₂F₃N₄O₄S
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Handling Instructions (2659 KB)

References

[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]

[2]. Kim J Y, et al. The Effects of KR-67607 on Intraocular Pressure and Glaucomatous Optic Neuropathy[J]. Investigative Ophthalmology & Visual Science, 2019, 60(9): 643-643.

[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]

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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