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Pathway Description
Ulobetasol Action Pathway
Homo sapiens
Drug Action Pathway
Ulobetasol, also known as Halobetasol, is a highly potent corticosteroid used to treat corticosteroid-responsive dermatoses. This drug is available as a topical cream, foam, spray, or ointment. Ulobetasol is a glucocorticoid receptor agonist and is structurally related to clobetasol. By binding to the glucocorticoid receptor, it influences transcription factors AP-1 and NF-kB to block the transcription of COX-2/prostaglandin G/H synthase 2 which reduces the amount of prostanoids being produced from arachidonic acid. Prostanoids such as PGI2 and thromboxane A2 influence the effects of inflammation through vasoconstriction/dilation, pain sensitivity, and platelet aggregation. This drug also affects the promoter of annexin-1, an important inflammatory protein as it affects leukocytes and blocks phospholipase A2 which reduces the amount of arachidonic acid being cleaved from the phospholipid bilayer. Reducing the amount of arachidonic acid formed further decreases the concentrations of prostanoids mentioned calming inflammation. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.
References
Ulobetasol Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Awad N, Preuss CV: Halobetasol Cream.
Pubmed: 31334954
Yasir M, Goyal A, Sonthalia S: Corticosteroid Adverse Effects.
Pubmed: 30285357
Czock D, Keller F, Rasche FM, Haussler U: Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44(1):61-98. doi: 10.2165/00003088-200544010-00003.
Pubmed: 15634032
Watson WA, Kalb RE, Siskin SB, Freer JP, Krochmal L: The safety of halobetasol 0.05% ointment in the treatment of psoriasis. Pharmacotherapy. 1990;10(2):107-11.
Pubmed: 2349135
Mohandas S, Rai R, Srinivas CR: Halobetasol versus clobetasol: a study of potency. Indian J Dermatol Venereol Leprol. 2009 Mar-Apr;75(2):186-7. doi: 10.4103/0378-6323.48672.
Pubmed: 19293512
Hofmann TG, Hehner SP, Bacher S, Droge W, Schmitz ML: Various glucocorticoids differ in their ability to induce gene expression, apoptosis and to repress NF-kappaB-dependent transcription. FEBS Lett. 1998 Dec 28;441(3):441-6. doi: 10.1016/s0014-5793(98)01609-3.
Pubmed: 9891987
Liu T, Zhang L, Joo D, Sun S. NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy 2: 17023, 2017.
Perretti M, D’Acquisto F. Annexin A1 and glucocorticoids as effectors of the resolution of
inflammation. Nature Reviews Immunology 9: 62–70, 2009.
Kirschke E, Goswami D, Southworth D, Griffin P. R, Agard D. Glucocorticoid Receptor Function Regulated by Coordinated Action of the Hsp90 and Hsp70 Chaperone Cycles. Cell 157(7): 1685-1697, 2014.
Oeckinghaus A, Ghosh S. The NF-kB Family of Transcription Factors and Its Regulation. Cold Spring Harb Perspect Biol 1(4): a000034, 2009.
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