Ajulemic acid

Ajulemic acid (1',1'-Dimethylheptyl-delta-8-tetrahydrocannabinol-11-oic acid) (DMH-D8-THC-11-OIC) (AB-III-56, HU-239, IP-751, CPL 7075, CT-3, JBT-101, Anabasum, Resunab, Lenabasum) is a synthetic cannabinoid that shows anti-fibrotic and anti-inflammatory effects in pre-clinical studies without causing a subjective "high".[1] Although its design was inspired by a metabolite of delta-9-THC known as delta-9-THC-11-oic acid, ajulemic acid is an analog of the delta-8-THC metabolite delta-8-THC-11-oic acid.[2][3] It is being developed for the treatment of inflammatory and fibrotic conditions such as systemic sclerosis, dermatomyositis and cystic fibrosis.[4] It does not share the anti-emetic effects of some other cannabinoids, but may be useful for treating chronic inflammatory conditions where inflammation fails to resolve.[5] Side effects include dry mouth, tiredness, and dizziness. The mechanism of action is through activation of the CB2 receptor leading to production of specialized proresolving eicosanoids such as lipoxin A4 and Prostaglandin J2. Studies in animals at doses up to 40 mg/kg show minimal psychoactivity of ajulemic acid, compared to that produced by tetrahydrocannabinol.[6] A composition of ajulemic acid named Lenabasum (formerly Anabasum, Resunab) is being developed by Corbus Pharmaceuticals (formerly JB Therapeutics) for the treatment of orphan chronic life-threatening inflammatory diseases.[7]

Ajulemic acid
Clinical data
Trade namesLenabasum
Routes of
administration		Oral
ATC code
  • None
Legal status
Legal status
  • Investigational
Pharmacokinetic data
MetabolismMinimal
Identifiers
IUPAC name
  • (6aR,10aR)-3-(1,1-Dimethylheptyl)-6a,7,10,10a-tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-carboxylic acid
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC25H36O4
Molar mass400.559 g·mol−1
3D model (JSmol)
SMILES
  • OC(C1=CC[C@](C(C)(C)OC2=C3C(O)=CC(C(C)(C)CCCCCC)=C2)([H])[C@@]3([H])C1)=O
InChI
  • InChI=1S/C25H36O4/c1-6-7-8-9-12-24(2,3)17-14-20(26)22-18-13-16(23(27)28)10-11-19(18)25(4,5)29-21(22)15-17/h10-11,14-16,18-19,26H,6-9,12-13H2,1-5H3,(H,27,28)/t16?,18-,19-/m1/s1 Y
  • Key:QHGPTMABBHVVQU-VOBHOPKGSA-N Y
 NY (what is this?)  (verify)

References
  1. Burstein SH, Karst M, Schneider U, Zurier RB (August 2004). "Ajulemic acid: A novel cannabinoid produces analgesia without a "high"". Life Sciences. 75 (12): 1513–22. doi:10.1016/j.lfs.2004.04.010. PMID 15240185.
  2. Vann, Robert E.; Cook, Charles D.; Martin, Billy R.; Wiley, Jenny L. (2007). "Cannabimimetic properties of ajulemic acid". The Journal of Pharmacology and Experimental Therapeutics. 320 (2): 678–686. doi:10.1124/jpet.106.111625. ISSN 0022-3565. PMID 17105826. S2CID 15593252.
  3. Motwani, Madhur P.; Bennett, Frances; Norris, Paul C.; Maini, Alexander A.; George, Marc J.; Newson, Justine; Henderson, Alice; Hobbs, Adrian J.; Tepper, Mark; White, Barbara; Serhan, Charles N. (2018). "Potent Anti-Inflammatory and Pro-Resolving Effects of Anabasum in a Human Model of Self-Resolving Acute Inflammation". Clinical Pharmacology and Therapeutics. 104 (4): 675–686. doi:10.1002/cpt.980. ISSN 1532-6535. PMC 6175297. PMID 29238967.
  4. Mitchell VA, Aslan S, Safaei R, Vaughan CW (July 2005). "Effect of the cannabinoid ajulemic acid on rat models of neuropathic and inflammatory pain". Neuroscience Letters. 382 (3): 231–5. doi:10.1016/j.neulet.2005.03.019. PMID 15925096. S2CID 582590.
  5. Burstein S (June 2005). "Ajulemic acid (IP-751): synthesis, proof of principle, toxicity studies, and clinical trials". The AAPS Journal. 7 (1): E143-8. doi:10.1208/aapsj070115. PMC 2751505. PMID 16146336.
  6. Vann RE, Cook CD, Martin BR, Wiley JL (February 2007). "Cannabimimetic properties of ajulemic acid". The Journal of Pharmacology and Experimental Therapeutics. 320 (2): 678–86. doi:10.1124/jpet.106.111625. PMC 2633725. PMID 17105826.
  7. "Companies To Watch: Corbus Pharmaceuticals". www.lifescienceleader.com. Retrieved 2019-05-20.
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