Olorinab

Olorinab (APD371) is a drug being developed by Arena Pharmaceuticals for the treatment of gastrointestinal pain associated with Crohn's disease and irritable bowel syndrome.[1] It acts as a potent and selective cannabinoid CB2 receptor agonist and is claimed to be orally active and peripherally selective.[2][3] Initial Phase IIa exploratory clinical trials have been successful in patients with quiescent Crohn's disease.[4] Arena initiated the Phase IIb Captivate[5] trial in late July 2019[6] in patients with irritable bowel syndrome related pain, in constipation and diarrhea predominant sub-types.[7] The Phase IIb trial is expected to enroll 240 participants between the ages of 18 to 70.Three doses of 10 mg, 25 mg, and 50 mg are being tested against Placebo in a 3:4 prescription ratio with a Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) masking layout.[8][9]

Olorinab
Clinical data
Routes of
administration		Oral
Identifiers
IUPAC name
  • (4aS,5aS)-N-((2S)-1-Hydroxy-3,3-dimethylbutan-2-yl)-1-(4-oxidopyrazin-2-yl)-4,4a,5,5a-tetrahydro-1H-cyclopropa(4,5)cyclopenta[1,2-c]pyrazole-3-carboxamide
CAS Number
PubChem CID
UNII
KEGG
Chemical and physical data
FormulaC18H23N5O3
Molar mass357.414 g·mol−1
3D model (JSmol)
SMILES
  • CC(C)(C)[C@@H](CO)NC(=O)C1=NN(C2=C1C[C@H]3[C@@H]2C3)C4=NC=C[N+](=C4)[O-]
InChI
  • InChI=1S/C18H23N5O3/c1-18(2,3)13(9-24)20-17(25)15-12-7-10-6-11(10)16(12)23(21-15)14-8-22(26)5-4-19-14/h4-5,8,10-11,13,24H,6-7,9H2,1-3H3,(H,20,25)/t10-,11-,13+/m0/s1
  • Key:ACSQLTBPYZSGBA-GMXVVIOVSA-N

In 2019, a study showed that Olorinab reduces Visceral Hypersensitivity in the TNBS-induced colitis animal model, attempting to control for its mechanism of action by using a CB2 antagonist (SR-144,528). Results were favorable showing reduced visceral hypersensitivity in animal models of IBD and IBS but not in healthy controls, suggesting that activation of CB2 causes antinociceptive actions in visceral sensory pathways in models of IBD and IBS. Also, SR-144528 prevented olorinab-induced inhibition of colonic nociceptor hypersensitivity, further validating the role of the CB2 receptor in nociception.[10]

See also

References
  1. "Arena Pharmaceuticals Presented New Phase 2 Data for Etrasimod and Olorinab at the 14th Congress of European Crohn's and Colitis Organisation". Arena Pharmaceuticals, Inc. Retrieved 2019-04-13.
  2. Han S, Thoresen L, Jung JK, Zhu X, Thatte J, Solomon M, et al. (December 2017). "Discovery of APD371: Identification of a Highly Potent and Selective CB2 Agonist for the Treatment of Chronic Pain". ACS Medicinal Chemistry Letters. 8 (12): 1309–1313. doi:10.1021/acsmedchemlett.7b00396. PMC 5733264. PMID 29259753.
  3. "Olorinab (APD371)". Arena Pharmaceuticals, Inc.
  4. "Arena Pharmaceuticals Reports Positive Phase 2a Results for Olorinab in Patients with Abdominal Pain Associated with Crohn's Disease". Arena Pharmaceuticals, Inc. Retrieved 2019-04-13.
  5. "Captivate study site". Captivate. Retrieved 2019-12-31.
  6. "Arena Pharmaceuticals Announces First Subject Dosed in CAPTIVATE Phase 2 Trial Evaluating Olorinab in Abdominal Pain Associated with Irritable Bowel Syndrome". Arena Pharmaceuticals, Inc. Retrieved 2019-12-31.
  7. "18th Annual Needham Healthcare Conference". wsw.com. Retrieved 2019-04-13.
  8. "Olorinab in IBS-C and IBS-D - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2019-12-31.
  9. "Development of olorinab, a cannabinoid type 2 receptor agonist, for the management of chronic abdominal pain disorders". Arena Pharmaceuticals.
  10. Castro J, Maddern J, Garcia-Caraballo S, Lumsden AL, Lindstrom B, Adams J, Brierley S (May 2019). "Sa1738 – Olorinab (Formerly Apd371), a Peripherally Restricted, Highly Selective, Full Agonist of the Cannabinoid Receptor 2 (CB2), Reduces Visceral Hypersensitivity in Animal Models". Gastroenterology. 156 (6): S–382. doi:10.1016/s0016-5085(19)37805-9. ISSN 0016-5085.
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