RPL-554 (LS-193,855) is a drug candidate for respiratory diseases. It is an analog of trequinsin and, like trequinsin, is a highly selective inhibitor of the

phosphodiesterase A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, ''phosphodiesterase'' refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many ot ...

enzyme, PDE3; indeed, it is >3000-times more potent against PDE3 than PDE4. As of October 2015, inhaled RPL-554 delivered via a

nebulizer In medicine, a nebulizer (American English) or nebuliser (British English) is a drug delivery device used to administer medication in the form of a mist inhaled into the lungs. Nebulizers are commonly used for the treatment of asthma, cystic fibro ...

was in development for COPD and had been studied in asthma.

PDE3 inhibitor A PDE3 inhibitor is a drug which inhibits the action of the phosphodiesterase enzyme PDE3. They are used for the therapy of acute heart failure and cardiogenic shock. Medical uses Cardiac Amrinone, milrinone and enoximone are used clinically f ...

s act as

bronchodilators A bronchodilator or broncholytic (although the latter occasionally includes secretory inhibition as well) is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs ...

, while

PDE4 inhibitor A phosphodiesterase-4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 (PDE4) on cyclic adenosine monophosphate (cAMP). It is a member of the larger family of PDE inhibitor ...

s have an anti-inflammatory effect. RPL554 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 Vernalis plc was a UK-based pharmaceuticals business headquartered in Winnersh, with research in Cambridge, and with a Berwyn, PA, US-based commercial operation, Vernalis Therapeutics Inc., focusing on the sales and marketing of slow-release ...

. 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 RPL-554, delivered with an

inhaler An inhaler (also known as a puffer, pump or allergy spray) is a medical device used for delivering medicines into the lungs through the work of a person's breathing. This allows medicines to be delivered to and absorbed in the lungs, which prov ...

, first for

allergic rhinitis Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, i ...

, then

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...

, then for

COPD Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...

. RPL554 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.

References

{{Phosphodiesterase inhibitors Phenol ethers Lactams Ureas Imines PDE4 inhibitors PDE3 inhibitors