HU-308
Very Potent CB2 Agonist Created in the Lab of Dr. Raphael Mechoulam
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC27H43O3
Molar mass415.638 g·mol−1
3D model (JSmol)
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Description & Background[edit]

HU-308 is a drug that acts as a potent cannabinoid agonist and which is a highly selective agonist for the CB2 receptor subtype in particular, with a selectivity of over 5,000 times greater for CB2 versus its selectivity for CB1.[1] The synthesis and characterization took place in the laboratory of Prof. Mechoulam at the Hebrew University of Jerusalem in the late 1990s. It has analgesic effects,[2] has an important functional outcome ~ the secretion of interleukins 6 (IL-6) and 10 (IL-10) with therapeutic immunomodulatory properties in vitro,[3] promotes proliferation of neural stem cells,[4] and protects both liver and blood vessel tissues against hepatic ischemia and reperfusion (blood circulatory) injury by attenuating oxidative stress, inflammatory response and apoptosis via inhibition of TNF-α.[5][6]

Researchers Dr. Melanie Kelly and Dr. C. Lehmann at Panag Pharma, now merged with Tetra Bio-Pharma, which owns the IP rights to HU-308, with Drs. J Sardinha and J Zhou showed that HU 308 also mediates immune modulation in sepsis,[7] as well as displays antiallodynic activity (alleviates allodynic pain) in the rat hindpaw incision model of post-operative pain, is neuroprotective and improves motor performance in a mouse model of Huntington's Disease.[8] Continued work by Dr. MEM Kelly et al showed HU-308 also dramatically fights the cytokine release syndrome (CRS), also called cytokine release storm, that is seen in many diseases and conditions, including ARDS (acute respiratory distress syndrome), pneumonia and others. HU-308, renamed ARDS-03, is currently being funded in a major collaboration study by partners Tetra Bio-Pharma and Targeted Pharmaceutical, LLC and further partnered with George Mason University and NIH using the university's top-level National Center for Biodefense and Infectious Diseases Biomedical Research Laboratory (BRL) against ARDS in COVID-19 patients[9][10][11][12][13][14].

Legal status[edit]

United States[edit]

HU-308 is not scheduled at the federal level in the United States.[15]

Florida[edit]

"HU-308 ([(1R,2R,5R)-2-[2,6-dimethoxy-4-(2-methyloctan-2-yl)phenyl]-7,7-dimethyl-4-bicyclo[3.1.1]hept-3-enyl]methanol)" is a Schedule I controlled substance in the state of Florida making it illegal to buy, sell, or possess in Florida.[16]

References[edit]

  1. ^ Hanus L, Breuer A, Tchilibon S, Shiloah S, Goldenberg D, Horowitz M, et al. (December 1999). "HU-308: a specific agonist for CB(2), a peripheral cannabinoid receptor". Proceedings of the National Academy of Sciences of the United States of America. 96 (25): 14228–33. Bibcode:1999PNAS...9614228H. doi:10.1073/pnas.96.25.14228. PMC 24419. PMID 10588688.
  2. ^ LaBuda CJ, Koblish M, Little PJ (December 2005). "Cannabinoid CB2 receptor agonist activity in the hindpaw incision model of postoperative pain". European Journal of Pharmacology. 527 (1–3): 172–4. doi:10.1016/j.ejphar.2005.10.020. PMID 16316653.
  3. ^ Saroz Y, Kho DT, Glass M, Graham ES, Grimsey NL (2019-10-19). "Cannabinoid Receptor 2 (CB 2 ) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes". ACS Pharmacology & Translational Science. 2 (6): 414–428. doi:10.1021/acsptsci.9b00049. ISSN 2575-9108. PMC 7088898. PMID 32259074.
  4. ^ Palazuelos J, Aguado T, Egia A, Mechoulam R, Guzmán M, Galve-Roperh I (November 2006). "Non-psychoactive CB2 cannabinoid agonists stimulate neural progenitor proliferation". FASEB Journal. 20 (13): 2405–7. doi:10.1096/fj.06-6164fje. PMID 17015409. S2CID 4885167.
  5. ^ Rajesh M, Pan H, Mukhopadhyay P, Bátkai S, Osei-Hyiaman D, Haskó G, et al. (December 2007). "Cannabinoid-2 receptor agonist HU-308 protects against hepatic ischemia/reperfusion injury by attenuating oxidative stress, inflammatory response, and apoptosis". Journal of Leukocyte Biology. 82 (6): 1382–9. doi:10.1189/jlb.0307180. PMC 2225476. PMID 17652447.
  6. ^ Rajesh M, Mukhopadhyay P, Bátkai S, Haskó G, Liaudet L, Huffman JW, et al. (October 2007). "CB2-receptor stimulation attenuates TNF-alpha-induced human endothelial cell activation, transendothelial migration of monocytes, and monocyte-endothelial adhesion". American Journal of Physiology. Heart and Circulatory Physiology. 293 (4): H2210-8. doi:10.1152/ajpheart.00688.2007. PMC 2229632. PMID 17660390.
  7. ^ Sardinha, Kelly, Zhou, Lehmann (2014). "Experimental cannabinoid 2 receptor-mediated immune modulation in sepsis". Mediators of Inflammation. PMID 24803745.
  8. ^ https://www.tocris.com/products/hu-308_3088
  9. ^ https://www.forbes.com/sites/emilyearlenbaugh/2020/08/20/synthetic-cannabinoid-drug-for-covid-19-approved-for-phase-1-clinical-trials/
  10. ^ https://s24.q4cdn.com/136309390/files/doc_presentation/2020/12/Tetra-Bio-Pharma-Milestones-Update-Dec.-30-2020.pdf
  11. ^ https://www.sedar.com/GetFile.do?lang=EN&docClass=7&issuerNo=00026458&issuerType=03&projectNo=03122925&docId=4813488
  12. ^ https://ir.tetrabiopharma.com/newsroom/press-releases/news-details/2020/Tetra-Bio-Pharma-Targeted-Pharmaceutical--the-George-Mason-University-Partner-on-ARDS-003-to-Prevent--Treat-COVID-19/default.aspx
  13. ^ https://science.gmu.edu/directory/lance-liotta
  14. ^ https://tetrabiopharma.com/partners/
  15. ^ 21 CFR — SCHEDULES OF CONTROLLED SUBSTANCES §1308.11 Schedule I.
  16. ^ Florida Statutes - Chapter 893 - DRUG ABUSE PREVENTION AND CONTROL

See also[edit]