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Ensifentrine

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Chemical compound

Pharmaceutical compound
Ensifentrine
Clinical data
Trade namesOhtuvayre
Other namesRPL-554, LS-193,855
AHFS/Drugs.comMultum Consumer Information
License data
Routes of
administration		Inhalation
Drug classPDE3 inhibitor/PDE4 inhibitor
ATC code
  • None
Legal status
Legal status
Identifiers
IUPAC name
  • N-{2--isoquinolin-3(4H)-yl]ethyl}urea
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard100.245.423 Edit this at Wikidata
Chemical and physical data
FormulaC26H31N5O4
Molar mass477.565 g·mol
3D model (JSmol)
SMILES
  • Cc3cc(C)cc(C)c3N=c2cc1-c(cc4OC)c(cc4OC)CCn1c(=O)n2CCNC(N)=O
InChI
  • InChI=1S/C26H31N5O4/c1-15-10-16(2)24(17(3)11-15)29-23-14-20-19-13-22(35-5)21(34-4)12-18(19)6-8-30(20)26(33)31(23)9-7-28-25(27)32/h10-14H,6-9H2,1-5H3,(H3,27,28,32)/b29-23+
  • Key:CSOBIBXVIYAXFM-BYNJWEBRSA-N
  (verify)

Ensifentrine, sold under the brand name Ohtuvayre, is a medication used for the treatment of chronic obstructive pulmonary disease (COPD) in adults. It is a phosphodiesterase 3 inhibitor and phosphodiesterase 4 inhibitor. It is given by inhalation.

PDE3 inhibitors act as bronchodilators, while PDE4 inhibitors have an anti-inflammatory effect.

Ensifentrine was approved for medical use in the United States in June 2024.

Medical uses

Ensifentrine is indicated for the maintenance treatment of chronic obstructive pulmonary disease in adults.

Pharmacology

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.

History

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.

In 2005, Rhinopharma Ltd, acquired the rights to the intellectual property from Vernalis. 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, and intended to develop ensifentrine, delivered with an inhaler, first for allergic rhinitis, then asthma, then for COPD. 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. In 2006 Rhinopharma recapitalized and was renamed Verona Pharma plc.

Society and culture

Legal status

Ensifentrine was approved for medical use in the United States in June 2024.

Research

As of October 2015, inhaled RPL-554 delivered via a nebulizer was in development for COPD and had been studied in asthma.

References

  1. ^ "Ohtuvayre- ensifentrine suspension". DailyMed. 18 June 2024. Retrieved 15 August 2024.
  2. ^ 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 isoquinolin-4-one] and RPL565 isoquinolin-4-one]". The Journal of Pharmacology and Experimental Therapeutics. 318 (2): 840–8. doi:10.1124/jpet.105.099192. PMID 16682455. S2CID 15490792.
  3. 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.
  4. ^ "Novel Drug Approvals for 2024". U.S. Food and Drug Administration (FDA). 1 October 2024. Retrieved 29 November 2024.
  5. 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.
  6. EP 1165558, Oxford AW, Jack D, "Derivatives of pyrimidoisoquinolin-4-one", published 2002-01-02, assigned to Verona Pharma plc 
  7. 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 isoquinolin-4-one] and RPL565 isoquinolin-4-one]". The Journal of Pharmacology and Experimental Therapeutics. 318 (2): 840–848. doi:10.1124/jpet.105.099192. PMID 16682455. S2CID 15490792.
  8. ^ "Proposed Acquisition of Rhinopharma" (PDF). Isis Resources plc. 23 August 2006. Archived from the original (PDF) on 2 March 2016.
  9. Taylor NP (1 October 2015). "Verona sets sights on PhIIb after COPD drug comes through early trial". FierceBiotech.
Drugs for obstructive airway diseases: asthma/COPD (R03)
Adrenergics, inhalants
Short-acting β2 agonists
Long-acting β2 agonists
Ultra-long-acting β2 agonists
Other
Glucocorticoids
Anticholinergics/
muscarinic antagonist
Mast cell stabilizers
Xanthines
Eicosanoid inhibition
Leukotriene antagonists
Arachidonate 5-lipoxygenase inhibitors
Thromboxane receptor antagonists
Non-xanthine PDE4 inhibitors
Others/unknown
Combination products
Phosphodiesterase inhibitors
PDE1
PDE2
PDE3
PDE4
PDE5
PDE7
PDE9
PDE10
PDE11BC11-38
Non-selective
Unsorted
See also: Receptor/signaling modulators
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