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{{Short description|Chemical compound}}
{{Drugbox
{{Drugbox
| Verifiedfields = changed
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 477315042
| verifiedrevid = 477315042
| 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
| IUPAC_name = (6a''R'',10a''R'')-3-(1,1-Dimethylheptyl)-6a,7,10,10a-tetrahydro-1-hydroxy-6,6-dimethyl-6''H''-dibenzo[''b'',''d'']pyran-9-carboxylic acid
| image = Ajulemicacid.png
| image = Ajulemic acid Structure.svg
| width = 200
| width =


<!--Clinical data-->
<!--Clinical data-->
| tradename = Resunab
| tradename = Lenabasum
| legal_status = patent pending
| legal_status = Investigational
| routes_of_administration = oral
| routes_of_administration = Oral


<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
| metabolism = minimal
| metabolism = Minimal
| elimination_half-life =
| elimination_half-life =
| excretion =
| excretion =
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| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 137945-48-3
| CAS_number = 137945-48-3
| ATC_prefix = none
| ATC_prefix = None
| PubChem = 3083542
| PubChem = 3083542
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 21106251
| ChemSpiderID = 21106251
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = OGN7X90BT8
| UNII = OGN7X90BT8
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL_Ref = {{ebicite|changed|EBI}}
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<!--Chemical data-->
<!--Chemical data-->
| C=25 | H=36 | O=4
| C=25 | H=36 | O=4
| smiles = OC(C1=CC[C@](C(C)(C)OC2=C3C(O)=CC(C(C)(C)CCCCCC)=C2)([H])[C@@]3([H])C1)=O
| molecular_weight = 400.551 g/mol
| smiles = CC(C)(CCCCCC)c2cc1OC(C)(C)[C@@H]3/C=C\C(C[C@H]3c1c(O)c2)C(O)=O
| InChI = 1/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
| InChIKey = QHGPTMABBHVVQU-VOBHOPKGBO
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChI = 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
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}}
}}


'''Lenabasum''' (also known as '''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''', and '''Resunab''') is a [[Chemical synthesis|synthetic]] [[cannabinoid]] that shows [[anti-fibrotic]] and [[anti-inflammatory]] effects in [[Pre-clinical development|pre-clinical studies]] without causing a subjective "high".<ref name="pmid15240185">{{cite journal | vauthors = Burstein SH, Karst M, Schneider U, Zurier RB | title = Ajulemic acid: A novel cannabinoid produces analgesia without a "high" | journal = Life Sciences | volume = 75 | issue = 12 | pages = 1513–1522 | date = August 2004 | pmid = 15240185 | doi = 10.1016/j.lfs.2004.04.010 }}</ref> Although its design was inspired by a [[metabolite]] of [[Tetrahydrocannabinol|delta-9-THC]] known as [[11-Nor-9-carboxy-THC|delta-9-THC-11-oic acid]], lenabasum is an [[Structural analog|analog]] of the [[Delta-8-Tetrahydrocannabinol|delta-8-THC]] metabolite delta-8-THC-11-oic acid.<ref>{{cite journal | vauthors = Vann RE, Cook CD, Martin BR, Wiley JL | title = Cannabimimetic properties of ajulemic acid | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 320 | issue = 2 | pages = 678–686 | date = February 2007 | pmid = 17105826 | doi = 10.1124/jpet.106.111625 | s2cid = 15593252 }}</ref><ref>{{cite journal | vauthors = Motwani MP, Bennett F, Norris PC, Maini AA, George MJ, Newson J, Henderson A, Hobbs AJ, Tepper M, White B, Serhan CN, MacAllister R, Gilroy DW | display-authors = 6 | title = Potent Anti-Inflammatory and Pro-Resolving Effects of Anabasum in a Human Model of Self-Resolving Acute Inflammation | journal = Clinical Pharmacology and Therapeutics | volume = 104 | issue = 4 | pages = 675–686 | date = October 2018 | pmid = 29238967 | pmc = 6175297 | doi = 10.1002/cpt.980 }}</ref> It is being [[drug development|developed]] for the treatment of inflammatory and fibrotic conditions such as systemic sclerosis, dermatomyositis and cystic fibrosis.<ref name="pmid15925096">{{cite journal | vauthors = Mitchell VA, Aslan S, Safaei R, Vaughan CW | title = Effect of the cannabinoid ajulemic acid on rat models of neuropathic and inflammatory pain | journal = Neuroscience Letters | volume = 382 | issue = 3 | pages = 231–235 | date = July 2005 | pmid = 15925096 | doi = 10.1016/j.neulet.2005.03.019 | s2cid = 582590 }}</ref> 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.<ref name="pmid16146336">{{cite journal | vauthors = Burstein S | title = Ajulemic acid (IP-751): synthesis, proof of principle, toxicity studies, and clinical trials | journal = The AAPS Journal | volume = 7 | issue = 1 | pages = E143–E148 | date = June 2005 | pmid = 16146336 | pmc = 2751505 | doi = 10.1208/aapsj070115 }}</ref> Side effects include dry mouth, tiredness, and dizziness. The mechanism of action is through activation of the [[CB2 receptor|CB<sub>2</sub> receptor]] leading to production of specialized proresolving eicosanoids such as [[lipoxin A4]] and [[prostaglandin J2]]. Studies in animals at doses up to 40&nbsp;mg/kg show minimal psychoactivity of lenabasum, compared to that produced by [[tetrahydrocannabinol]].<ref>{{cite journal | vauthors = Vann RE, Cook CD, Martin BR, Wiley JL | title = Cannabimimetic properties of ajulemic acid | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 320 | issue = 2 | pages = 678–686 | date = February 2007 | pmid = 17105826 | pmc = 2633725 | doi = 10.1124/jpet.106.111625 }}</ref> Lenabasum is being developed by Corbus Pharmaceuticals (formerly JB Therapeutics) for the treatment of orphan chronic life-threatening inflammatory diseases.<ref>{{Cite web|url=https://www.lifescienceleader.com/doc/corbus-pharmaceuticals-0001|title=Companies To Watch: Corbus Pharmaceuticals|website=www.lifescienceleader.com|access-date=2019-05-20}}</ref> Development since been discontinued.<ref>{{cite web | url = https://adisinsight.springer.com/drugs/800007180 | title = Lenabasum | work = AdisInsight }}</ref>
'''Ajulemic acid''' (AB-III-56, HU-239, IP-751, CPL 7075, CT-3, Resunab) is a [[Chemical synthesis|synthetic]] [[cannabinoid]] derivative of the non-psychoactive [[Tetrahydrocannabinol|THC]] [[metabolite]] [[Tetrahydrocannabinol#Metabolism|11-nor-9-carboxy-THC]] that shows useful [[analgesic]] and [[anti-inflammatory]] effects without causing a subjective "high".<ref name="pmid15240185">{{Cite journal
| volume = 75
| journal = Life Sciences
| issue = 12
| pages = 1513–1522
| doi = 10.1016/j.lfs.2004.04.010
| pmid = 15240185
| year = 2004
| title = Ajulemic acid: A novel cannabinoid produces analgesia without a "high"
| last1 = Burstein | first1 = S.
| last2 = Karst | first2 = M.
| last3 = Schneider| first3 = U.
| last4 = Zurier | first4 = R.
}}</ref> It is being developed for the treatment of [[neuropathic]] pain and inflammatory conditions such as [[arthritis]].<ref name="pmid15925096">{{Cite journal
| last1 = Mitchell| first1 = V.
| last2 = Aslan| first2 = S.
| last3 = Safaei | first3 = R.
| last4 = Vaughan | first4 = C.
| title = Effect of the cannabinoid ajulemic acid on rat models of neuropathic and inflammatory pain
| journal = Neuroscience Letters
| volume = 382
| issue = 3
| pages = 231–235
| year = 2005
| pmid = 15925096
| doi = 10.1016/j.neulet.2005.03.019
}}</ref> It does not however share the [[anti-emetic]] effects of other cannabinoids but may be useful for treating pain and chronic inflammatory conditions where nausea is not present.<ref name="pmid16146336">{{Cite journal
| year = 2005
| pmid = 16146336
| pmc = 2751505
| doi = 10.1208/aapsj070115
| pages = E143–E148
| issue = 1
| title = Ajulemic acid (IP-751): synthesis, proof of principle, toxicity studies, and clinical trials
| journal = The AAPS journal
| volume = 7
| last1 = Burstein| first1 = S.
}}</ref> Side effects include dry mouth, tiredness and dizziness. The mechanism of action has not yet been fully established, but ajulemic acid may activate the [[CB2 receptor|CB<sub>2</sub> receptor]] in the periphery leading to production of resolving eicosanoids. Studies in animals at doses up to 40&nbsp;mg/kg show minimal psychoactivity of ajulemic acid, comparable to that produced by [[tetrahydrocannabinol]],.<ref>{{Cite journal
| pages = 678–686
| issue = 2
| volume = 320
| last4 = Wiley
| year = 2007
| pmid = 17105826
| doi = 10.1124/jpet.106.111625
| last1 = Vann
| pmc = 2633725
| journal = The Journal of Pharmacology and Experimental Therapeutics
| title = Cannabimimetic properties of ajulemic acid
| first2 = C.
| last3 = Martin | first3 = B.
| last2 = Cook | first4 = J.| first1 = R.
}}</ref> Likewise, there was no difference between ajulemic acid and placebo on the "cannabimimetic" assay when used in humans at therapeutic doses.<ref>{{Cite journal
| author= Sumariwalla | first= P.
| last2= Gallily | first2= R.
| last3= Tchilibon | first3= S.
| last4= Fride | first4= E.
| last5= Mechoulam | first5= R.
| last6= Feldmann | first6= M. |title= A novel synthetic, nonpsychoactive cannabinoid acid (HU-320) with antiinflammatory properties in murine collagen-induced arthritis |journal= Arthritis and rheumatism |volume= 50 |issue= 3 |pages= 985–998 |year= 2004 |pmid= 15022343 |doi= 10.1002/art.20050 }}
</ref><ref>{{Cite journal |title= Reply |journal= Arthritis & Rheumatism |volume= 50 |year= 2004 |issue= 12 |pages= 4079–4080 |author= Sumariwalla, P.F.|doi= 10.1002/art.20806 |display-authors=etal}}
</ref> A new highly purified composition of ajulemic acid named Resunab is being developed by Corbus Pharmaceuticals (formerly JB Therapeutics)for the treatment of orphan life-threatening inflammatory diseases.


== References ==
== References ==
{{Reflist}}
<references />


{{Cannabinoids}}
{{Cannabinoids}}
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[[Category:Benzochromenes]]
[[Category:Benzochromenes]]
[[Category:Carboxylic acids]]
[[Category:Carboxylic acids]]
[[Category:Phenols]]
[[Category:Hydroxyarenes]]
[[Category:HU cannabinoids]]
[[Category:HU cannabinoids]]
[[Category:Abandoned drugs]]

Latest revision as of 16:20, 21 October 2024

Lenabasum
Clinical data
Trade namesLenabasum
Routes of
administration		Oral
ATC code
  • None
Legal status
Legal status
  • Investigational
Pharmacokinetic data
MetabolismMinimal
Identifiers
  • (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)
  • OC(C1=CC[C@](C(C)(C)OC2=C3C(O)=CC(C(C)(C)CCCCCC)=C2)([H])[C@@]3([H])C1)=O
  • 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 checkY
  • Key:QHGPTMABBHVVQU-VOBHOPKGSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Lenabasum (also known as 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, and Resunab) 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, lenabasum 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 lenabasum, compared to that produced by tetrahydrocannabinol.[6] Lenabasum is being developed by Corbus Pharmaceuticals (formerly JB Therapeutics) for the treatment of orphan chronic life-threatening inflammatory diseases.[7] Development since been discontinued.[8]

References

[edit]
  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): 1513–1522. doi:10.1016/j.lfs.2004.04.010. PMID 15240185.
  2. ^ Vann RE, Cook CD, Martin BR, Wiley JL (February 2007). "Cannabimimetic properties of ajulemic acid". The Journal of Pharmacology and Experimental Therapeutics. 320 (2): 678–686. doi:10.1124/jpet.106.111625. PMID 17105826. S2CID 15593252.
  3. ^ Motwani MP, Bennett F, Norris PC, Maini AA, George MJ, Newson J, et al. (October 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. 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): 231–235. 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–E148. 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): 678–686. doi:10.1124/jpet.106.111625. PMC 2633725. PMID 17105826.
  7. ^ "Companies To Watch: Corbus Pharmaceuticals". www.lifescienceleader.com. Retrieved 2019-05-20.
  8. ^ "Lenabasum". AdisInsight.
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