Ensifentrine
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MedKoo CAT#: 584481

CAS#: 1884461-72-6

Description: Ensifentrine, also known as VMX 554 and RPL-554, is a novel, selective, dual phosphodiesterase (PDE)3 and PDE4 inhibitor with bronchodilator and anti-inflammatory effects. Ensifentrine may have beneficial anti-inflammatory effects in CF airways particularly when used in combination with β 2-adrenergic agonists or corticosteroids.

Chemical Structure

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Ensifentrine
CAS# 1884461-72-6
Instruction

Theoretical Analysis

MedKoo Cat#: 584481
Name: Ensifentrine
CAS#: 1884461-72-6
Chemical Formula: C26H31N5O4
Exact Mass: 477.24
Molecular Weight: 477.565
Elemental Analysis: C, 65.39; H, 6.54; N, 14.67; O, 13.40

Price and Availability

Size Price Availability Quantity
5mg USD 450 2 Weeks
10mg USD 750 2 Weeks
25mg USD 1250 2 Weeks
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Synonym: Ensifentrine; RPL 554; RPL-554; RPL554; VMX 554; VMX-554; VMX554;

IUPAC/Chemical Name: N-(2-{(2E)-9,10-dimethoxy-4-oxo-2-[(2,4,6-trimethylphenyl)imino]-6,7-dihydro-2H-pyrimido[6,1-a]isoquinolin-3(4H)-yl}ethyl)urea

InChi Key: CSOBIBXVIYAXFM-BYNJWEBRSA-N

InChi Code: 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+

SMILES Code: O=C(N)NCCN1C(N(CCC2=C3C=C(OC)C(OC)=C2)C3=C/C1=N\C4=C(C)C=C(C)C=C4C)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.03.00

More Info:

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 477.57 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
In vivo protocol:

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1: Donohue JF, Rheault T, MacDonald-Berko M, Bengtsson T, Rickard K. Ensifentrine as a Novel, Inhaled Treatment for Patients with COPD. Int J Chron Obstruct Pulmon Dis. 2023 Jul 28;18:1611-1622. doi: 10.2147/COPD.S413436. PMID: 37533771; PMCID: PMC10392818.


2: Stolfa I, Page C. Phosphodiesterase inhibitors and lung diseases. Adv Pharmacol. 2023;98:55-81. doi: 10.1016/bs.apha.2023.05.001. Epub 2023 May 26. PMID: 37524492.


3: Singh D. A New Treatment for Chronic Obstructive Pulmonary Disease: Ensifentrine Moves Closer. Am J Respir Crit Care Med. 2023 Aug 15;208(4):344-346. doi: 10.1164/rccm.202307-1164ED. PMID: 37433204; PMCID: PMC10449076.


4: Anzueto A, Barjaktarevic IZ, Siler TM, Rheault T, Bengtsson T, Rickard K, Sciurba F. Ensifentrine, a Novel Phosphodiesterase 3 and 4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease: Randomized, Double-Blind, Placebo-controlled, Multicenter Phase III Trials (the ENHANCE Trials). Am J Respir Crit Care Med. 2023 Aug 15;208(4):406-416. doi: 10.1164/rccm.202306-0944OC. PMID: 37364283; PMCID: PMC10449067.


5: Calzetta L, Pistocchini E, Chetta A, Rogliani P, Cazzola M. Experimental drugs in clinical trials for COPD: artificial intelligence via machine learning approach to predict the successful advance from early-stage development to approval. Expert Opin Investig Drugs. 2023 Jan-Jun;32(6):525-536. doi: 10.1080/13543784.2023.2230138. Epub 2023 Jul 6. PMID: 37364225.


6: Antoniu SA, Handra CM, Rascu A, Barbu BA, Chirap Mitulschi I. Navafenterol for chronic obstructive pulmonary disease therapy. Expert Opin Investig Drugs. 2023 Apr;32(4):283-290. doi: 10.1080/13543784.2023.2199920. PMID: 37017626.


7: Goonathilake MR, Waqar S, George S, Jean-Baptiste W, Yusuf Ali A, Inyang B, Koshy FS, George K, Poudel P, Chalasani R, Mohammed L. Can Phosphodiesterase 4 Inhibitor Therapy Be Used in Respiratory Diseases Other Than Chronic Obstructive Pulmonary Disease? Cureus. 2022 Jul 22;14(7):e27132. doi: 10.7759/cureus.27132. PMID: 36017299; PMCID: PMC9392891.


8: Singh D, Lea S, Mathioudakis AG. Inhaled Phosphodiesterase Inhibitors for the Treatment of Chronic Obstructive Pulmonary Disease. Drugs. 2021 Nov;81(16):1821-1830. doi: 10.1007/s40265-021-01616-9. Epub 2021 Nov 3. PMID: 34731461.


9: Martin C, Burgel PR, Roche N. Inhaled Dual Phosphodiesterase 3/4 Inhibitors for the Treatment of Patients with COPD: A Short Review. Int J Chron Obstruct Pulmon Dis. 2021 Aug 16;16:2363-2373. doi: 10.2147/COPD.S226688. PMID: 34429594; PMCID: PMC8378910.


10: Ferguson GT, Kerwin EM, Rheault T, Bengtsson T, Rickard K. A Dose-Ranging Study of the Novel Inhaled Dual PDE 3 and 4 Inhibitor Ensifentrine in Patients with COPD Receiving Maintenance Tiotropium Therapy. Int J Chron Obstruct Pulmon Dis. 2021 Apr 22;16:1137-1148. doi: 10.2147/COPD.S307160. PMID: 33911859; PMCID: PMC8075181.


11: Turner MJ, Abbott-Banner K, Thomas DY, Hanrahan JW. Cyclic nucleotide phosphodiesterase inhibitors as therapeutic interventions for cystic fibrosis. Pharmacol Ther. 2021 Aug;224:107826. doi: 10.1016/j.pharmthera.2021.107826. Epub 2021 Mar 1. PMID: 33662448.


12: Turner MJ, Dauletbaev N, Lands LC, Hanrahan JW. The Phosphodiesterase Inhibitor Ensifentrine Reduces Production of Proinflammatory Mediators in Well Differentiated Bronchial Epithelial Cells by Inhibiting PDE4. J Pharmacol Exp Ther. 2020 Dec;375(3):414-429. doi: 10.1124/jpet.120.000080. Epub 2020 Oct 4. PMID: 33012706.


13: Watz H, Rickard K, Rheault T, Bengtsson T, Singh D. Symptom Improvement Following Treatment with the Inhaled Dual Phosphodiesterase 3 and 4 Inhibitor Ensifentrine in Patients with Moderate to Severe COPD - A Detailed Analysis. Int J Chron Obstruct Pulmon Dis. 2020 Sep 16;15:2199-2206. doi: 10.2147/COPD.S263025. PMID: 32982212; PMCID: PMC7502392.


14: Turner MJ, Luo Y, Thomas DY, Hanrahan JW. The dual phosphodiesterase 3/4 inhibitor RPL554 stimulates rare class III and IV CFTR mutants. Am J Physiol Lung Cell Mol Physiol. 2020 May 1;318(5):L908-L920. doi: 10.1152/ajplung.00285.2019. Epub 2020 Mar 11. PMID: 32159371.


15: Singh D, Martinez FJ, Watz H, Bengtsson T, Maurer BT. A dose-ranging study of the inhaled dual phosphodiesterase 3 and 4 inhibitor ensifentrine in COPD. Respir Res. 2020 Feb 10;21(1):47. doi: 10.1186/s12931-020-1307-4. PMID: 32041601; PMCID: PMC7011474.


16: Cazzola M, Calzetta L, Rogliani P, Matera MG. Ensifentrine (RPL554): an investigational PDE3/4 inhibitor for the treatment of COPD. Expert Opin Investig Drugs. 2019 Oct;28(10):827-833. doi: 10.1080/13543784.2019.1661990. Epub 2019 Sep 1. PMID: 31474120.


17: Bjermer L, Abbott-Banner K, Newman K. Efficacy and safety of a first-in- class inhaled PDE3/4 inhibitor (ensifentrine) vs salbutamol in asthma. Pulm Pharmacol Ther. 2019 Oct;58:101814. doi: 10.1016/j.pupt.2019.101814. Epub 2019 Jun 14. PMID: 31202957.


18: Cazzola M, Page C, Calzetta L, Matera MG. Ensifentrine (RPL554): an inhaled 'bifunctional' dual PDE3/4 inhibitor for the treatment of asthma and chronic obstructive pulmonary disease. Pharm Pat Anal. 2018 Nov;7(6):249-257. doi: 10.4155/ppa-2018-0030. Epub 2019 Jan 18. PMID: 30657422.


19: Cazzola M, Page C. An inhaled "bifunctional" dual PDE3/4 inhibitor provides additional short-term improvements in lung function compared to existing classes of bronchodilator: implications for future treatment of COPD. Eur Respir J. 2018 Nov 1;52(5):1801675. doi: 10.1183/13993003.01675-2018. PMID: 30385603.


20: Singh D, Abbott-Banner K, Bengtsson T, Newman K. The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD. Eur Respir J. 2018 Nov 1;52(5):1801074. doi: 10.1183/13993003.01074-2018. PMID: 30166326; PMCID: PMC6214575.