Ensifentrine
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| Clinical data | |
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| Trade names | Ohtuvayre |
| Other names | RPL-554, LS-193,855 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a624040 |
| License data |
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| Routes of administration | Inhalation |
| Drug class | PDE3 inhibitor/PDE4 inhibitor |
| ATC code |
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| Legal status | |
| Legal status | |
| Identifiers | |
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| CAS Number | |
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| DrugBank | |
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| Chemical and physical data | |
| Formula | C26H31N5O4 |
| Molar mass | 477.565 g·mol−1 |
| 3D model (JSmol) | |
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Ensifentrine, sold under the brand name Ohtuvayre, is a medication used for the treatment of chronic obstructive pulmonary disease (COPD) in adults.[1] It is a phosphodiesterase 3 inhibitor and phosphodiesterase 4 inhibitor.[1] It is given by inhalation.[1]
PDE3 inhibitors act as bronchodilators, while PDE4 inhibitors have an anti-inflammatory effect.[2][3]
Ensifentrine was approved for medical use in the United States in June 2024.[1][4][5]
Medical uses
[edit]Ensifentrine is indicated for the maintenance treatment of chronic obstructive pulmonary disease in adults.[1]
Pharmacology
[edit]It is an analog of trequinsin and, like trequinsin, it is a highly selective inhibitor of the phosphodiesterase enzyme, PDE3; it is >3000-times more potent against PDE3 than PDE4.[2]
History
[edit]Ensifentrine was part of a family of compounds invented by Sir David Jack, former head of R&D for GlaxoSmithKline, and Alexander Oxford, a medicinal chemist; the patents on their work were assigned to Vernalis plc.[6][7][8]: 19–20
In 2005, Rhinopharma Ltd, acquired the rights to the intellectual property from Vernalis.[8]: 19–20 Rhinopharma was a startup founded in Vancouver, Canada in 2004 by Michael Walker, Clive Page, and David Saint, to discover and develop drugs for chronic respiratory diseases,[8]: 16 and intended to develop ensifentrine, delivered with an inhaler, first for allergic rhinitis, then asthma, then for chronic obstructive pulmonary disease.[8]: 16–17 Ensifentrine was synthesized at a contract research organization, under the supervision of Oxford, and was studied in collaboration with Page's lab at King’s College, London.[2] In 2006 Rhinopharma recapitalized and was renamed Verona Pharma plc.[8]
Society and culture
[edit]Legal status
[edit]Ensifentrine was approved for medical use in the United States in June 2024.[1][4]
References
[edit]- ^ a b c d e f g "Ohtuvayre- ensifentrine suspension". DailyMed. 18 June 2024. Retrieved 15 August 2024.
- ^ a b c Boswell-Smith V, Spina D, Oxford AW, Comer MB, Seeds EA, Page CP (August 2006). "The pharmacology of two novel long-acting phosphodiesterase 3/4 inhibitors, RPL554 [9,10-dimethoxy-2(2,4,6-trimethylphenylimino)-3-(n-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one] and RPL565 [6,7-dihydro-2-(2,6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido[6,1-a]isoquinolin-4-one]". The Journal of Pharmacology and Experimental Therapeutics. 318 (2): 840–8. doi:10.1124/jpet.105.099192. PMID 16682455. S2CID 15490792.
- ^ Turner MJ, Matthes E, Billet A, Ferguson AJ, Thomas DY, Randell SH, et al. (January 2016). "The dual phosphodiesterase 3 and 4 inhibitor RPL554 stimulates CFTR and ciliary beating in primary cultures of bronchial epithelia". American Journal of Physiology. Lung Cellular and Molecular Physiology. 310 (1): L59-70. doi:10.1152/ajplung.00324.2015. PMID 26545902.
- ^ a b "Novel Drug Approvals for 2024". U.S. Food and Drug Administration (FDA). 1 October 2024. Archived from the original on 19 April 2024. Retrieved 29 November 2024.
- ^ New Drug Therapy Approvals 2024 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2025. Archived from the original on 21 January 2025. Retrieved 21 January 2025.
- ^ EP 1165558, Oxford AW, Jack D, "Derivatives of pyrimido[6,1-a]isoquinolin-4-one", published 2 January 2002, assigned to Verona Pharma plc
- ^ Boswell-Smith V, Spina D, Oxford AW, Comer MB, Seeds EA, Page CP (August 2006). "The pharmacology of two novel long-acting phosphodiesterase 3/4 inhibitors, RPL554 [9,10-dimethoxy-2(2,4,6-trimethylphenylimino)-3-(n-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one] and RPL565 [6,7-dihydro-2-(2,6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido[6,1-a]isoquinolin-4-one]". The Journal of Pharmacology and Experimental Therapeutics. 318 (2): 840–848. doi:10.1124/jpet.105.099192. PMID 16682455. S2CID 15490792.
- ^ a b c d e "Proposed Acquisition of Rhinopharma" (PDF). Isis Resources plc. 23 August 2006. Archived from the original (PDF) on 2 March 2016.
