Lenabasum

Last updated
Lenabasum
Ajulemic acid Structure.svg
Clinical data
Trade names Lenabasum
Routes of
administration
Oral
ATC code
  • None
Legal status
Legal status
  • Investigational
Pharmacokinetic data
Metabolism Minimal
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
Formula C25H36O4
Molar mass 400.559 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 Yes check.svgY
  • Key:QHGPTMABBHVVQU-VOBHOPKGSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (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]

Related Research Articles

<span class="mw-page-title-main">Cannabinoid</span> Compounds found in cannabis

Cannabinoids are several structural classes of compounds found in the cannabis plant primarily and most animal organisms or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoactive compound in cannabis. Cannabidiol (CBD) is also a major constituent of temperate cannabis plants and a minor constituent in tropical varieties. At least 113 distinct phytocannabinoids have been isolated from cannabis, although only four have been demonstrated to have a biogenetic origin. It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort, and earlier in Echinacea.

<span class="mw-page-title-main">Tetrahydrocannabivarin</span> Homologue of tetrahydrocannabinol

Tetrahydrocannabivarin is a homologue of tetrahydrocannabinol (THC) having a propyl (3-carbon) side chain instead of pentyl (5-carbon), making it non-psychoactive in lower doses. It has been shown to exhibit neuroprotective activity, appetite suppression, glycemic control and reduced side effects compared to THC, making it a potential treatment for management of obesity and diabetes. THCV was studied by Roger Adams as early as 1942.

<span class="mw-page-title-main">WIN 55,212-2</span> Chemical compound

WIN 55,212-2 is a chemical described as an aminoalkylindole derivative, which produces effects similar to those of cannabinoids such as tetrahydrocannabinol (THC) but has an entirely different chemical structure.

<span class="mw-page-title-main">11-Hydroxy-THC</span> Active metabolite of Δ9-THC

11-Hydroxy-Δ9-tetrahydrocannabinol, usually referred to as 11-hydroxy-THC is the main active metabolite of tetrahydrocannabinol (THC), which is formed in the body after Δ9-THC is consumed.

<span class="mw-page-title-main">Cannabigerol</span> Minor cannabinoid

Cannabigerol (CBG) is a non-psychoactive cannabinoid and minor constituent of cannabis. It is one of more than 120 identified cannabinoids found in the plant genus Cannabis. The compound is the decarboxylated form of cannabigerolic acid (CBGA), the parent molecule from which other cannabinoids are biosynthesized.

<span class="mw-page-title-main">NAGly receptor</span> Protein-coding gene in the species Homo sapiens

N-Arachidonyl glycine receptor, also known as G protein-coupled receptor 18 (GPR18), is a protein that in humans is encoded by the GPR18 gene. Along with the other previously orphan receptors GPR55 and GPR119, GPR18 has been found to be a receptor for endogenous lipid neurotransmitters, several of which also bind to cannabinoid receptors. It has been found to be involved in the regulation of intraocular pressure.

<span class="mw-page-title-main">JWH-200</span> Chemical compound

JWH-200 (WIN 55,225) is an analgesic chemical from the aminoalkylindole family that acts as a cannabinoid receptor agonist. Its binding affinity, Ki at the CB1 receptor is 42 nM, around the same as that of THC, but its analgesic potency in vivo was higher than that of other analogues with stronger CB1 binding affinity in vitro, around 3 times that of THC but with less sedative effect, most likely reflecting favourable pharmacokinetic characteristics. It was discovered in 1991 by Sterling Drug as a potential analgesic following the earlier identification of related compounds such as pravadoline and WIN 55,212-2.

<span class="mw-page-title-main">11-Nor-9-carboxy-THC</span> Main secondary metabolite of THC

11-Nor-9-carboxy-Δ9-tetrahydrocannabinol, often referred to as 11-nor-9-carboxy-THC or THC-11-oic acid, is the main secondary metabolite of tetrahydrocannabinol (THC) which is formed in the body after cannabis is consumed.

<span class="mw-page-title-main">Surinabant</span> Chemical compound

Surinabant (SR147778) is a cannabinoid receptor type 1 antagonist developed by Sanofi-Aventis. It is being investigated as a potential treatment for nicotine addiction, to assist smoking cessation. It may also be developed as an anorectic drug to assist with weight loss, however there are already several CB1 antagonists or inverse agonists on the market or under development for this application, so surinabant is at present mainly being developed as an anti-smoking drug, with possible application in the treatment of other addictive disorders such as alcoholism. Other potential applications such as treatment of ADHD have also been proposed.

<span class="mw-page-title-main">Cannabichromene</span> Chemical compound

Cannabichromene (CBC), also called cannabichrome, cannanbichromene, pentylcannabichromene or cannabinochromene, exhibits anti-inflammatory properties in vitro, which may, theoretically, contribute to cannabis analgesic effects. It is a phytocannabinoid, one of the hundreds of cannabinoids found in the Cannabis plant. It bears structural similarity to the other natural cannabinoids, including tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV), cannabidiol (CBD), and cannabinol (CBN), among others. CBC and cannabinols are present in cannabis. It is not scheduled by the Convention on Psychotropic Substances.

<i>N</i>-Acylethanolamine Class of chemical compounds

An N-acylethanolamine (NAE) is a type of fatty acid amide where one of several types of acyl groups is linked to the nitrogen atom of ethanolamine, and highly metabolic formed by intake of essential fatty acids through diet by 20:4, n-6 and 22:6, n-3 fatty acids, and when the body is physically and psychologically active,. The endocannabinoid signaling system (ECS) is the major pathway by which NAEs exerts its physiological effects in animal cells with similarities in plants, and the metabolism of NAEs is an integral part of the ECS, a very ancient signaling system, being clearly present from the divergence of the protostomian/deuterostomian, and even further back in time, to the very beginning of bacteria, the oldest organisms on Earth known to express phosphatidylethanolamine, the precursor to endocannabinoids, in their cytoplasmic membranes. Fatty acid metabolites with affinity for CB receptors are produced by cyanobacteria, which diverged from eukaryotes at least 2000 Million years ago (MYA), by brown algae which diverged about 1500 MYA, by sponges, which diverged from eumetazoans about 930 MYA, and a lineages that predate the evolution of CB receptors, as CB1 – CB2 duplication event may have occurred prior to the lophotrochozoan-deuterostome divergence 590 MYA. Fatty acid amide hydrolase (FAAH) evolved relatively recently, either after the evolution of fish 400 MYA, or after the appearance of mammals 300 MYA, but after the appearance of vertebrates. Linking FAAH, vanilloid receptors (VR1) and anandamide implies a coupling among the remaining ‘‘older’’ parts of the endocannabinoid system, monoglyceride lipase (MGL), CB receptors, that evolved prior to the metazoan–bilaterian divergence, but were secondarily lost in the Ecdysozoa, and 2-Arachidonoylglycerol (2-AG).

<span class="mw-page-title-main">Dronabinol</span> Generic name of Δ9-THC in medicine

Dronabinol, sold under the brand names Marinol and Syndros, is the generic name for the molecule of delta-9-tetrahydrocannabinol (THC) in the pharmaceutical context. It has indications as an appetite stimulant, antiemetic, and sleep apnea reliever and is approved by the U.S. FDA as safe and effective for HIV/AIDS-induced anorexia and chemotherapy-induced nausea and vomiting.

<span class="mw-page-title-main">O-1812</span> Chemical compound

O-1812 is an eicosanoid derivative related to anandamide that acts as a potent and highly selective agonist for the cannabinoid receptor CB1, with a Ki of 3.4 nM at CB1 and 3870 nM at CB2. Unlike most related compounds, O-1812 is metabolically stable against rapid breakdown by enzymes, and produces a cannabinoid-like discriminative effect in rats, which is similar but not identical to that produced by cannabinoid drugs of other chemical classes.

<span class="mw-page-title-main">Tetrahydrocannabinolic acid</span> THC precursor

Tetrahydrocannabinolic acid is a precursor of tetrahydrocannabinol (THC), an active component of cannabis.

<span class="mw-page-title-main">Tetrahydrocannabiphorol</span> Cannabinoid agonist compound

Tetrahydrocannabiphorol (THCP, pronounced ) is a potent phytocannabinoid, a CB1 and CB2 agonist which was known as a synthetic homologue of THC, but for the first time in 2019 was isolated as a natural product in trace amounts from Cannabis sativa. It is structurally similar to Δ9-THC, the main active component of cannabis, but with the pentyl side chain extended to heptyl. Since it has a longer side chain, its cannabinoid effects are "far higher than Δ9-THC itself." Tetrahydrocannabiphorol has a reported binding affinity of 1.2 nM at CB1, approximately 33 times that of Δ9-THC (40 nM at CB1).

<span class="mw-page-title-main">Δ-8-Tetrahydrocannabinol</span> Isomer of tetrahydrocannabinol

Δ-8-tetrahydrocannabinol is a psychoactive cannabinoid found in the Cannabis plant. It is an isomer of delta-9-tetrahydrocannabinol, the compound commonly known as THC, with which it co-occurs in hemp; natural quantities of ∆8-THC found in hemp are low. Psychoactive effects are similar to that of Δ9-THC, with central effects occurring by binding to cannabinoid receptors found in various regions of the brain.

<span class="mw-page-title-main">8,11-Dihydroxytetrahydrocannabinol</span> Chemical compound

8,11-Dihydroxytetrahydrocannabinol (8β,11-diOH-Δ9-THC) is an active metabolite of THC, the main active component of cannabis. The 8β enantiomer retains psychoactive effects in animal studies with only slightly lower potency than THC, while the 8α enantiomer is much weaker. Both enantiomers have a shorter half-life in the body than 11-hydroxy-THC, making 8,11-dihydroxy-THC potentially useful for drug testing to distinguish between recent cannabis use and use longer in the past.

<span class="mw-page-title-main">11-Hydroxy-Δ-8-THC</span> Metabolite of delta-8-THC

11-Hydroxy-Δ-8-tetrahydrocannabinol is an active metabolite of Δ8-THC, a psychoactive cannabinoid found in small amounts in cannabis. It is an isomer of 11-OH-Δ9-THC, and is produced via the same metabolic pathway. It was the first cannabinoid metabolite discovered in 1970.

<span class="mw-page-title-main">11-Hydroxyhexahydrocannabinol</span> Chemical compound

11-Hydroxyhexahydrocannabinol is an active metabolite of tetrahydrocannabinol (THC) and a metabolite of the trace cannabinoid hexahydrocannabinol (HHC).

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): 1513–1522. 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.