P1-185 Explained
P1-185, also known as progesterone 3-O-(L-valine)-E-oxime or as pregn-4-ene-3,20-dione 3-O-(L-valine)-E-oxime, is a synthetic progestogen and neurosteroid and an oxime ester analogue and prodrug of progesterone (and by extension of allopregnanolone).[1] [2] It was developed as an improved water-soluble version of progesterone such that it could be formulated as an aqueous preparation and easily and rapidly administered intravenously as a potential therapy for traumatic brain injury. However, the chemical synthesis of P1-185 was described as somewhat challenging, so oxime conjugates of progesterone of the C20 instead of C3 position, such as EIDD-1723 and EIDD-036, have since been developed.[3] [4]
See also
- List of neurosteroids § Inhibitory > Synthetic > Pregnanes
- List of progestogen esters § Oximes of progesterone derivatives
Notes and References
- MacNevin CJ, Atif F, Sayeed I, Stein DG, Liotta DC . Development and screening of water-soluble analogues of progesterone and allopregnanolone in models of brain injury . J. Med. Chem. . 52 . 19 . 6012–23 . 2009 . 19791804 . 10.1021/jm900712n .
- Guthrie DB, Stein DG, Liotta DC, Lockwood MA, Sayeed I, Atif F, Arrendale RF, Reddy GP, Evers TJ, Marengo JR, Howard RB, Culver DG, Natchus MG . Water-soluble progesterone analogues are effective, injectable treatments in animal models of traumatic brain injury . ACS Med Chem Lett . 3 . 5 . 362–6 . 2012 . 24900479 . 4025794 . 10.1021/ml200303r .
- Wali B, Sayeed I, Guthrie DB, Natchus MG, Turan N, Liotta DC, Stein DG . Evaluating the neurotherapeutic potential of a water-soluble progesterone analog after traumatic brain injury in rats . Neuropharmacology . 109 . 148–158 . October 2016 . 27267687 . 10.1016/j.neuropharm.2016.05.017 . 19906601 .
- Guthrie, D. B., Lockwood, M. A., Natchus, M. G., Liotta, D. C., Stein, D. G., & Sayeed, I. (2017). U.S. Patent No. 9,802,978. Washington, DC: U.S. Patent and Trademark Office. https://patents.google.com/patent/US9802978B2/en
