Next Article in Journal
Oviductal Extracellular Vesicles Improve Post-Thaw Sperm Function in Red Wolves and Cheetahs
Previous Article in Journal
Liquid Biopsy for the Diagnosis of Viral Hepatitis, Fatty Liver Steatosis, and Alcoholic Liver Diseases
Article

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

1
Therapeutics & Biotechnology Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Korea
2
Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea
3
Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 61005, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3729; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103729
Received: 30 April 2020 / Revised: 18 May 2020 / Accepted: 21 May 2020 / Published: 25 May 2020
(This article belongs to the Section Biochemistry)
Dry eye syndrome is the most common eye disease and it is caused by various reasons. As the balance of the tear film that protects the eyes is broken due to various causes, it becomes impossible to properly protect the eyes. In this study, the protective effects and underlying mechanisms of topical (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), a novel selective 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor, were investigated in benzalkonium chloride (BAC)-induced dry eye syndrome. BAC-treated rat eyes induced significant increases in ocular surface damage, decreased corneal thickness, corneal basement membrane destruction in the conjunctival epithelium, and expression of pro-inflammatory cytokines tumor necrosis factor-α and 11β-HSD1. These effects of BAC were reversed by topical KR-67607 treatment. Furthermore, KR-67607 decreased 4-hydroxynonenal expression and increased antioxidant and mucus secretion in BAC-treated rat eyes. Taken together, a novel selective 11β-HSD1 inhibitor can prevent BAC-induced dry eye syndrome by inhibiting pro-inflammatory cytokine and reactive oxygen species expression via the inhibition of both 11β-HSD1 activity and expression. View Full-Text
Keywords: dry eye syndrome; 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1); reactive oxygen species (ROS) dry eye syndrome; 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1); reactive oxygen species (ROS)
Show Figures

Graphical abstract

MDPI and ACS Style

Na, Y.-J.; Choi, K.J.; Jung, W.H.; Park, S.B.; Kang, S.; Ahn, J.H.; Kim, K.Y. 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, 3729. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103729

AMA Style

Na Y-J, Choi KJ, Jung WH, Park SB, Kang S, Ahn JH, Kim KY. 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. International Journal of Molecular Sciences. 2020; 21(10):3729. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103729

Chicago/Turabian Style

Na, Yoon-Ju, Kyoung J. Choi, Won H. Jung, Sung B. Park, Sein Kang, Jin H. Ahn, and Ki Y. Kim 2020. "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" International Journal of Molecular Sciences 21, no. 10: 3729. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103729

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop