UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

2018-04-01

Document Type

Article

Disciplines

Immune System Diseases | Medical Pharmacology | Medicinal and Pharmaceutical Chemistry | Medicinal Chemistry and Pharmaceutics | Pathological Conditions, Signs and Symptoms | Pharmaceutical Preparations | Pharmacology | Therapeutics

Abstract

Ajulemic acid (AJA, CT-3, IP-751, JBT-101, anabasum) is a first-in-class, synthetic, orally active, cannabinoid-derived drug that preferentially binds to the CB2 receptor and is nonpsychoactive. In preclinical studies, and in Phase 1 and 2 clinical trials, AJA showed a favorable safety, tolerability, and pharmacokinetic profile. It also demonstrated significant efficacy in preclinical models of inflammation and fibrosis. It suppresses tissue scarring and stimulates endogenous eicosanoids that resolve chronic inflammation and fibrosis without causing immunosuppression. AJA is currently being developed for use in 4 separate but related indications including systemic sclerosis (SSc), cystic fibrosis, dermatomyositis (DM), and systemic lupus erythematosus. Phase 2 clinical trials in the first 3 targets demonstrated that it is safe, is a potential treatment for these orphan diseases and appears to be a potent inflammation-resolving drug with a unique mechanism of action, distinct from the nonsteroidal anti-inflammatory drug (NSAID), and will be useful for treating a wide range of chronic inflammatory diseases. It may be considered to be a disease-modifying drug unlike most NSAIDs that only provide symptomatic relief. AJA is currently being evaluated in 24-month open-label extension studies in SSc and in skin-predominant DM. A Phase 3 multicenter trial to demonstrate safety and efficacy in SSc has recently been initiated.

Keywords

CB2, antimetastatic, disease-modifying, inflammation-resolving, systemic sclerosis

Rights and Permissions

© 2018 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

DOI of Published Version

10.1002/prp2.394

Source

Pharmacol Res Perspect. 2018 Apr;6(2):e00394. doi: 10.1002/prp2.394. Link to article on publisher's site

Journal/Book/Conference Title

Pharmacology research and perspectives

Related Resources

Link to Article in PubMed

PubMed ID

29638269

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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