Cannabinoid Signaling

The receptors CB1 and CB2 can be activated by endogenous, synthetic, and plant . Cayman Chemical offers a broad collection of assay kits, antibodies, and ligands to study these receptors and related .

CB₁-SELECTIVE AGONISTS CB₂-SELECTIVE AGONISTS

OH HO CH3 CANNABINOID HO H Cl H H H O O N N N HO N OH H

O O O O H

O O O O R-1 Arachidonoyl Arachidonoyl N-Arachidonoyl RECEPTORS JWH 133 L-759,633 HU-308 2’-Chloroethylamide Cyclopropylamide Dopamine 10 20 CB K = 677 nM CB K = 1,043 nM CB K = 75.4 nM CB K = >10,000 nM CB K = 17.9 - 28.3 nM CB K = 1.4 nM CB K = 2.2 nM CB K = 250 nM 1 i 1 i 1 i 1 i 1 i 1 i 1 i 1 i M K S I L D G L A D T T F R T I T T D L L Y V G S N D I CB K = 3.4 nM CB K = 6.4 nM CB K = 62.8 nM CB K = 22.7 nM CB K = 815 - 868 nM CB K = >2,000 nM CB K = 715 nM CB K = 12,000 nM Q 2 i 2 i 2 i 2 i 2 i 2 i 2 i 2 i Y 30

50 40 O NO E O 2 Q F P S G R F S T L P F K Q P F Y G L K S A M D G K I D 60 E Request a copy of the Cannabinoid N 70 80 10 K N M T A G D N P Q L V P A D Q V N I T E F Y N K S L M E E C W V T E I A N G S K N N F N O O O S D N N 100 90 20 NO2 OH S G N O Cl N C E I D M F N E G C Q I N E E N E K F D K M P N S D L N O F Y N O OH 110 M M 180 N V I N S V C S D I C S E L O Cl L H R M N L H G P L S I Cl 2-Arachidonyl Glycerol AM1235 JWH 073 Q F F N 180 F 370 K K F V 100 T D CB K = 1.5 nM CB K = 8.9 nM K L P S R P ether 1 i 1 i 260 JWH 015 AM1241 LY2828360 GW 405833 P V D K H 270 G L 30 G V D P L T Q CB K = 20.4 nM CB K = 38 nM CB K = 21.2 nM 2 i 2 i CB K = 383 nM CB K = 580 nM CB K = Not reported CB K = 2.04 µM 1 i S H S E I F I P H S C I 270 A V 1 i 1 i 1 i 1 i CB K = >3,000 nM CB K = 13.8 nM CB K = 7.1 nM CB K = 40.3 nM CB K = 14 nM 2 i Q F R C D V K Q F K C P L K 2 i 2 i 2 i 2 i extracellular Q D N N E D T K N A T N S K

L I V W T Y V T V V W D H 280 A A F A F F G Y V F F G 190 Y A F I L 190 L V 90 L 170 M L wall poster at 120 S L M 380 A A S L L M A A F M L F L F CB₁-SELECTIVE ANTAGONISTS/INVERSE AGONISTS V Y K F I V C K S L CB₂-SELECTIVE INVERSE AGONISTS P P C L A I 110 W A C L V L W A 40 C S G 250 L 280 I G L L S 170 360 S F Y L M F V L M T S L Cl L I G G L V V Cl A V S L O T V V L L F O O O O T P L V T I 260 P L V I T V C N N N H C G M A N N N N G S A V S G S L F L

L I O T S V L T F 200 O N H N H N H G I W A A W 290 I N F 200 F L L L F L N O N N N O N 130 A L H N T L T L C S T S F C N N H I N L 160 O Cl Cl Cl N S 390 S N Cl I I V L A L I A F A S I N L S T F L 120 S V G N D I T D 80 L M O N 290 E V I E A V W I 50 A W 240 L V L V N G M V N G M I O O Cl Cl Cl Cl N V S Y N L V S L Y V G I V L 160 L P A L T P A C A V 350 A G A SR 144528 AM630 IMMA AM251 AM281 PSNCBAM-1 V L F F Y L I V L L L Y L V L M L L 210 G CB K = 5.6 nM CB K = 7.5 nM CB K = 12 nM CB K = 0.1 µM L A I I CB K = 305 - >10,000 nM CB K = 5,152 nM CB K = >20 µM 1 i 1 i 1 i 1 i C S I Y S T H 250 V 1 i 1 i 1 i G T 210 V Y L G T V L Y 140 Y CB K = 0.3 - 5.6 nM CB K = 31.2 nM CB K = 435 nM CB2 Ki = >1,000 nM CB2 Ki = 2,290 nM CB2 Ki = 4,200 nM CB2 Ki = ≥10 µM V I L V 2 i 2 i 2 i I I A V L V A I I A L L G A 300 www.caymanchem.com/literature I A 150 A L F W L L L F I W L L O

H H D K 300 K T R 400 60 S L 130 D R K T R O cytoplasm O S Y R P A K S S Y 70 R G A K S N O N N Cl Cl Cl H R S Y R 230 H A K H S Y R H A G O N O O O O O N S I S L D Q P L T Q L E O H N P T O O O N NC N L O S V C N L R 150 H 340 R L L K H R I N H I I L L H N 220 N N N 2 CF3 R C A I R R R 140 V V R JTE-907 Ridaifen-B H R R A 240 H R P L A Y K V D H Y P P S Y K A D S Cl Cl Cl O Cl 220 CB1 Ki = 2,370 nM CB1 Ki = 732 nM 310 R M S M A L L S CB K = 35.9 nM CB K = 43.7 nM I I I S K Q T G R Q I G S 2 i 2 i R F Q H R A 310 NESS 0327 AM4113 LY320135 320 A D M H 330 R 410 CB K = 0.35 pM CB K = 0.89 nM CB K = 224 nM CB K = 0.13 nM Q R R H 1 i 1 i 1 i 1 i T S E D G K V Q V T R P D S Q V P G M A H M C CB2 Ki = 21 nM CB2 Ki = 92 nM CB2 Ki = >10,000 nM CB2 Ki = 170 nM 230 440 430 420 F 330 320 L S A A N N A H K H L C D S D G M S N D L P Q A T G E C S P S S R P A E E K A E S G L G R V C K K W H A V V 450 460 470 CB₂ RECEPTOR DISTRIBUTION H T R A A E S C I K S T V K I A K V T M S V S T D T S A E A L E T E A D G K I T P W P D S R D L D L S D C CB₁ RECEPTOR DISTRIBUTION 340 350 360 EXPRESSION FUNCTION (lymph, spleen, thymus, tonsils) · Mediates cytokine release and immune suppression EXPRESSION FUNCTION HUMAN CB1 RECEPTOR HUMAN CB2 RECEPTOR · Leukocytes · Mediates effects through anti-inflammatory activity Brain (especially on presynaptic GABAergic terminals) · Reduces inhibitory neurotransmission to modulate · T and B lymphocytes · Induces cell migration · Hippocampus cognition, memory, and motor function HUMAN CB & CB altered in mouse, rat S-palmitoylation site toggle switches for G protein binding · Monocytes, macrophages, dendritic cells 1 2 · Regulates phagocytosis · Cerebral cortex · Regulates hypothermia glycosylation sites phosphorylation sites critical role in G & G protein coupling specificity contacts (polar & non-polar)* · Mast cells RECEPTOR KEY s i · Induces apoptosis · Lateral caudate putamen · Modulates dopaminergic reward pathway and addiction Antibodies · Substantia nigra pars reticulata · Induces analgesia Neuronal somatodendritic areas (postsynaptic) · Reduces ventral tegmental area neuronal excitability and · Globus pallidus, entopeduncular nucleus -seeking behavior · Cerebellum MIXED CB₁/CB₂ AGONISTS MIXED CB₁/CB₂ ANTAGONISTS · Modulates hippocampal plasticity and synchronization · Hypothalamus · Substrate for neuroprotection · CNS pain pathways OH Spinal cord, dorsal root ganglion, activated microglia · Modulates neuropathic pain and neuroinflammation OH COOH OH OH OH OH HO H H H H Dorsal horn of spinal cord, primary sensory nerve terminals · Induces analgesia O OH H H H H Vagus nerve · Activates vagal C and/or Aδ fibers N O O OH Item No. Product Name Summary Adipocytes, skeletal muscle cells · Increases de novo lipogenesis O O O O OH · Promotes antitussive actions · Regulates lipid/ metabolism and insulin signaling Δ9-THCB Δ9-THC Δ8-THC Δ9-THCP · Blocks emesis HO

CB1 Ki = 15 nM CB1 Ki = 5.05 - 80.3 nM CB1 Ki = 28.5 nM CB1 Ki = 1.2 nM CB1 Ki = 440 nM Hematopoietic stem and progenitor cells · Promotes hematopoiesis and cell mobilization Mitochondria of striated and heart muscles · Regulates intramitochondrial signaling and respiration CB2 Ki = 51 nM CB2 Ki = 3.13 - 75.3 nM CB2 Ki = 25 nM CB2 Ki = 6.2 nM CB2 Ki = 337 nM JWH 018 N-(5-hydroxypentyl) CB K = 4,350 - >10,000 nM β-D-Glucuronide 1 i CB K = 2,399 - >10,000 nM Osteoblasts, osteocytes, osteoclasts · Modulates bone formation and turnover Heart/Vasculature (cardiomyocytes, endothelial cells, · Regulates blood flow, eliciting hypotension, CB1 Ki = 922 nM 2 i OH OH HO H CB2 Ki not reported inflammatory cells) bradycardia, and negative inotropy N O OH Endothelial cells, smooth muscle cells, cardiomyocytes, · Cardioprotective through anti-inflammatory and O O

O macrophages in atherosclerotic plaques antifibrotic actions Lung (alveolar macrophages, dendritic cells) · Decreases immune functions O OH OH 2-Arachidonoyl Glycerol Arachidonoyl Ethanolamide 10006590 CB Receptor (C-Term) Polyclonal Antibody Host: Rabbit • SpeciesSpleen, thymus Reactivity:· Roles in noradrenergic splenic contraction and(+) the Human, mouse, rat • Applications: IHC,Kupffer cells WB in the liver · Mediates hepatoprotection CB K = 713.7 nM CB K = 120 - 1,130 nM CB K = 25.3 - 472 nM 1 i 1 i 1 i () 1 neuroimmune axis HO · Promotes hemoglobin metabolism CB2 Ki = 256.52 nM CB2 Ki = 96.3 - 301 nM CB K = 145 - 1,400 nM 2 i CB1 Ki = 61 - 543 nM CB K = 279 - 1,940 nM Small intestine · Stimulates appetite 2 i Intestinal epithelial cells · Modulates intestinal inflammatory responses and CB1 Ki = 14,711 nM O CB K = 574.2 nM gut motility · Inhibits gastrointestinal activity O OH OH 2 i N N OH OH N N OH Keratinocytes, fibroblasts · Resolves peripheral inflammation Liver · Upregulation associated with liver disease O H O O * Comprehensive list of residues within distance ≤3.5 Å of bound ligands in CB crystal structures H 1 · Promotes tissue repair 5TGZ1, 5XR82, 5XRA2 and CB cryo-EM structure 6PT03. Kidney · Roles in renal function and dysfunction O 2 HO 1. Hua, T., Vemuri, K., Pu, M., et al. Crystal structure of the human cannabinoid receptor CB1. Retina · Upregulated under pathological conditions to modulate 101500 CB Receptor Polyclonal Antibody Host: Rabbit • SpeciesUrinary bladder, vas deferens Reactivity:· Modulates the release of neurotransmitters from(+) Human,(+)-WIN 55,212-2 HU-210 mouse,(–)-CP 55,940 JWH rat 018 JWH• 018 Applications: Cell 167(3), 750-762 (2016). IHC, WB retinal signaling CB K = 62.3 nM CB K = 0.1 - 0.73 nM CB K = 0.5 - 5 nM CB K = 9 nM 1 afferent nerves 1 i 1 i 1 i 1 i N-(5-hydroxypentyl) 2. Hua, T., Vemuri, K., Nikas, S.P., et al. Crystal structures of agonist-bound human CB2 Ki = 3.3 nM CB2 Ki = 0.17 - 0.524 nM CB2 Ki = 0.69 - 2.8 nM CB2 Ki = 2.94 nM metabolite cannabinoid receptor CB1. Nature 547(7664), 468-471 (2017). Tumors · Induces apoptosis in glioma cells CB K = 25.2 nM Testis, uterus · Modulates reproductive processes 1 i 3. Xing, C., Zhuang, Y., Xu, T.-H., et al. Cryo-EM structure of the human cannabinoid receptor · Increases cell proliferation in other cancers CB2 Ki = 47.4 nM CB2-Gi signaling complex. Cell 180(4), 645-654 (2020).

View a complete list of binding affinity references at www.caymanchem.com/CBreceptors Cirrhotic liver · Triggers antifibrogenic effects, including growth inhibition and apoptosis Learn More at www.caymanchem.com/CBsignalingreview © Cayman Chemical Company · Revised August 2020 101550 CB2 Receptor Polyclonal Antibody Host: Rabbit • Species Reactivity: (+) Human, mouse • Applications: IHC, WB

10010712 CB2 Receptor Polyclonal FITC Antibody Host: Rabbit • Species Reactivity: (+) Human • Applications: FC, IF

Endocannabinoids FAAH AA ethanolamine AEA Cayman offers a diverse collection of tools to study CB1 PLD NAPE endogenous ligands for the cannabinoid receptors, DAGL DAG arachidonoyl ethanolamide (AEA; Item No. 90050) 2-AG glycerol CB2 and 2-arachidonoyl glycerol (2-AG; Item No. 62160), MAGL AA as well as enzymes that synthesize and degrade these ABHD6 endocannabinoids. Endocannabinoid synthesis and hydrolysis NAPE-PLD Antibodies Item No. Product Name Summary

10305 NAPE-PLD (Internal) Polyclonal Antibody Host: Rabbit • Species Reactivity: (+) Human, mouse, rat • Application: WB

10306 NAPE-PLD (N-Term) Polyclonal Antibody Host: Rabbit • Species Reactivity: (+) Human, bovine, mouse, rat • Application: WB

MAGL Protein, Antibodies, and Assay Kit Item No. Product Name Summary

Source: Active human recombinant C-terminal His-tagged protein expressed in E. coli 10007812 Monoacylglycerol (human, recombinant) MW: 39 kDa

10212 (FL) Polyclonal Antibody Host: Rabbit • Species Reactivity: (+) Human, rat • Applications: ICC, IHC, WB

100035 Monoacylglycerol Lipase Polyclonal Antibody Host: Rabbit • Species Reactivity: (+) Human, bovine, mouse, rat • Applications: IHC, WB

Monoacylglycerol Lipase Inhibitor Screening 705192 A convenient colorimetric method for screening human MAGL inhibitors Assay Kit

2021 CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 WWW.CAYMANCHEM.COM MAGL Substrate and Inhibitors Item No. Product Name Summary

10007904 Arachidonoyl-1-thio-Glycerol A chromogenic substrate for measurement of MAGL activity

A selective MAGL inhibitor (IC s = 8 nM and 4 µM for MAGL and FAAH in mouse brain 13158 JZL 184 50 membranes, respectively)

11777 KML29 A selective inhibitor of mouse, rat, and human MAGL (IC50s = 15, 43, and 5.9 nM, respectively) A selective inhibitor of MAGL (IC = 80 nM) that inhibits the growth of some cancer cells 27348 MAGL Inhibitor Compound 23 50 in vitro and increases 2-AG in mouse brain and plasma

17583 MJN110 An N-hydroxysuccinimidyl carbamate that inhibits MAGL (IC50 = 9.1 nM)

13621 Pristimerin A naturally occurring terpenoid that inhibits MAGL (IC50 = 93 nM) View additional MAGL inhibitors at www.caymanchem.com DAGL Inhibitors Item No. Product Name Summary

18933 KT109 A selective inhibitor of DAGLβ (IC50 = 42 nM)

16419 LEI-106 An in vitro inhibitor of sn-1 DAGLα (IC50 = 18 nM)

14009 O-7460 A selective inhibitor of DAGLα (IC50 = 690 nM)

10005426 An inhibitor of human recombinant DAGLα (IC50 = 60 nM)

16432 RHC-80267 A selective inhibitor of DAGL (IC50 = 4 µM in canine platelets)

ABHD6 Inhibitors Item No. Product Name Summary

A potent inhibitor of ABHD6 (IC s = 1.7, 15.1, and 0.24 nM using Neuro2a membrane 15404 KT182 50 proteomes, recombinant ABHD6 in HEK293T cells, and Neuro2a cells in situ, respectively)

14818 KT195 A selective inhibitor of ABHD6 (IC50 = 10 nM)

16849 WWL123 A brain-penetrant inhibitor of ABHD6 (IC50 = 0.43 µM) View additional ABHD6 inhibitors at www.caymanchem.com FAAH Protein, Antibody, and Assay Kit Item No. Product Name Summary

10010183 Amide Hydrolase (human, recombinant) Source: Human recombinant C-terminal His-tagged protein expressed in Sf21 cells • MW: 64.3 kDa

101600 Fatty Acid Amide Hydrolase Polyclonal Antibody Host: Rabbit • Species Reactivity: (+) Human, mouse, rat • Applications: IHC, WB

Fatty Acid Amide Hydrolase Inhibitor Screening 10005196 A convenient fluorescence-based method for screening FAAH inhibitors Assay Kit

FAAH Inhibitors Item No. Product Name Summary

10005102 CAY10435 A selective inhibitor of rat FAAH (Ki = 0.57 nM)

A potent, irreversible FAAH inhibitor (IC50s = 70 and 313 nM for human and rat forms, 19987 JNJ-42165279 respectively) with activity in vivo, blocking FAAH activity in brain and periphery of rats and raising concentrations of endocannabinoids

An irreversible FAAH inhibitor (IC = 7.3 nM for the human recombinant when tested 10008661 JP104 50 using radiolabeled )

13279 PF-3845 A selective, irreversible inhibitor of FAAH (Ki = 0.23 μM)

19306 PF-04457845 An orally active, irreversible FAAH inhibitor (IC50 = 7.2 nM) A selective FAAH inhibitor (IC s = 4.6 and 0.5 nM in brain membranes and intact 10046 URB597 50 neurons, respectively)

View additional FAAH inhibitors at www.caymanchem.com

2021 CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 WWW.CAYMANCHEM.COM Cannabinoid Transport Item No. Product Name Summary

90060 AM404 A blocker of AEA reuptake with an IC50 of 1 µM in rat neurons and 5 µM in rat astrocytes

90052 Arvanil Agonist activity potentiator of endogenous cannabinoids by inhibiting the reuptake of AEA

10005072 CAY10455 A fluorescent substrate for AEA transport

10007072 1-Palmitoyl-2-linoleoyl PE A substrate used in studies involving the biosynthesis of AEA

View additional cannabinoid transport modulators at www.caymanchem.com

Phytocannabinoids Cayman offers analytical standards for the many prominent phytocannabinoids unique to the plant as well as their metabolites, newly identified homologs, and impurities. Cayman also offers multi-component standard mixtures to help expedite analysis.

PHYTOCANNABINOID GUIDE NAMING BIOSYNTHESIS, NAMING, AND NUMBERING NUMBERING CONVENTIONS CONVENTIONS When naming phytocannabinoids, the prefix “cannabi” always appears in the main scaffold which CLASSIC OLIVETOL SERIES The two most common conventions for numbering THC are the dibenzopyran and 1 drives the name and acronym of each compound. The resorcinol root will designate the original C5 monoterpene systems.2,3 The biphenyl and Lord Alexander Todd numbering series and its C3 and C1 homologs. Listed here are the main scaffolds observed in phytocannabinoids. Olivetolic phytocannabinoids are considered classic, as these are systems are older and less common.2,3 A simple terpenoid numbering system is Because of the prevalence of the olivetolic root, the standard names will all contain the suffix -OL or used for CBC, CBG, CBE, and CBL structures.3,4 –NOL, with a few exceptions. When describing the C3 and C1 homologs, the scaffold name is amended the compounds that are ubiquitous to all varietals of marijuana. This Request a copy of the Phytocannabinoid Guide: by dropping the -OL and replacing the suffix with -VARIN/VARINOL (C3) or -ORCIN/ORCINOL (C1). series is not only the most dominant in the Cannabis species but Most Common Systems The orcinolic series is unique in that the suffix has also been placed within the scaffold name (-ORC- as in cannabichromene → cannabiorcochromene). OH also the most widely studied in the literature. OH Dibenzopyran Numbering Monoterpene Numbering

11 7

9 Resorcinol Root Name O HO 6 8 10 1 Δ8- (Δ8-THC) OH 6 2 5 7 OH OH OH Cannabidiol (CBD) H 1 5 3 8 (ISO60158 | 14042) 6a 2' (ISO60156 | 90080) 7 4 4 2' 10a 2 1' 3 3' 1' H 3' OH O 8 2 3 HO HO HO H OH 6 6' H O 4' 6' Olivetol Divarin Orcinol OH 5 4 10 9 1 4' 7 5' 5' -OL -VARIN, -VARINOL -ORCIN, -ORCINOL, -ORC- OH 11 11 7 H O 9 9 O 9 9 8 8 10 OH Δ -Tetrahydrocannabinolic Acid A (THCA-A) (Δ -THCA-A) 10 OH 2 6 OH O OH OH Main Scaffold Motifs and Names (ISO60175) H H 5 3 (CBL) 1 1 2' 5 3 HO 7 6a 7 6a 4 4 2' (22036 | 9002438) 10a 2 10a 2 1' 1' Cannabigerol (CBG) (E isomer) OH 3' 3' Monocyclic Bicyclic Tricyclic Tetracyclic H H OH (20164 | 15293) 8 8 O 3 3 6' 6 O 6 O 4' 6' OH 9 9 Cannabinerol (CBNR) (Z isomer) HO 9 4' OH HO 5 4 5 4 10 10 9 OH Δ -Tetrahydrocannabinol (THC) (Δ -THC) 5' 5' OH O (CBND) (ISO60157 | 12068) (CBDA) Δ8 Δ9 Δ6 Δ1(2) O (18090) (9002479) Monoterpene numbering designates the dibenzopyran Δ8 HO R O R Dibenzopyran numbering designates the double bond of O R 6 9 1 2 OR HO R 8 9 configuration as Δ . The dibenzopyran Δ configuration is Δ (or Δ ). CannaBiGerol O OH interest as Δ or Δ . CannaBiChromene CBG CannaBiNol iso-TetraHydroCannabinol CannaBicycLol 9 9 CBC Δ -Tetrahydrocannabinolic Acid B (Δ -THCA-B) CBN iso-THC CBL HO HO HO Older/Less Common SystemsTerpenoid System HO OH OH OH OH OH OH O OH OH O Biphenyl Numbering Terpenoid Numbering

OH Biosynthesis, Naming, and Numbering wall 10' 9' O R 1' 1 OH R OR OR O 10' 6 HO 2' 2 1 O HO 3 7' 5' 1' 4 2 6 CannaBiciTran 3' 2 TetraHydroCannabinol CannaBiTriol 7' 5' CannaBiDiol Cannabitriol (CBT) (triol) Cannabiripsol (CBR) (CBE) 5 1 3' 5 3 8' 6' 4' 2' ‘Citran’ CBT 2' THC ‘Triol’ CBT 6 O CBD (21092) 1' 8' 4' 4 5 3 3' 6' 9' HO HO CBDA 4 THCA O Cannabichromene 6' 4' Cannabigerol synthase (CBC) OH O O synthase OH 5' (CBG) Todd Numbering 7 HO HO

R 1 O R R H HO HO Cannabifuran (CBF) O 6 2 1' OH HO 2' H 7' 5 3 6' 1 CannaBiNoDiol CannaBiElsoin CannaBiFuran Cannabichromene (CBC) 5' 4 2' 6 6' 3' 5' 1' 2 CBND CBE CBF (ISO60163 | 26252) 4' 6' 6" 4' H OH O 3' 1' 8 5 OH 2' 1" 5' 4' 3' 3 5" HO 4 O OH 5 HO OH 3 10 9 4 OH 2 1 4" Cannabicyclol 2" Cannabielsoin O O (CBE) (CBL) O OH 3" Cannabinolic Acid (CBNA) OR Cannabinol (CBN) OH O OH O (ISO60183 | 25495) anna i ipsol C B R OH OH 2. Mechoulam, R. and Gaoni, Y. Fortschr. Chem. Org. Naturst. 25, 175-213 (1967). CBR O 3. ElSohly, M.A. and Slade, D. Life Sci. 78(5), 539-548 (2005). CBCA O HO exo-Tetrahydrocannabinol (exo-THC) HO 4. Hanuš, L.O., Meyer, S.M., Muñoz, E., et al. Nat. Prod. Rep. 33(12), 1357-1392 (2016). “M” is indicative of methyl ester when added to the end of the acronym (CBGA) (E isomer) synthase (CBCA) OH (20019 | 9001572) (30879 | 9001573) (e.g., CBDM = cannabidiol methyl ester). “A” is indicative of the carboxylated O Cannabinerolic Acid (CBNRA) (Z isomer) O and is added to the very end of the acronym (e.g., THCA = tetrahydrocannabinolic acid). HO HO O poster at 1. Brenneisen, R. Chemistry and analysis of phytocannabinoids and other Cannabis Cannabielsorcinol (CBEO) Cannabinodiorcin (CBNDO) www.caymanchem.com/literature Cannabicitran (CBT) (citran) constituents. Marijuana and the Cannabinoids. ElSohly, M.A., editor, Humana Press (2007). OH (21295) O OH O

OH HO HO Cannabinodivarin (CBNDV) OH Cannabifuraorcin (CBFO) Cannabidiorcin (CBDO) Heat, Light, and Biosynthesis Cannabifuravarin (CBFV) Also known as O-1821 (10006804) Oxidation Exposure Geranyl- Enzymes transferase OH OH O O OH

OH OH HO Cannabidivarin (CBDV) HO (20165 | 9001574) OH Cannabidiorcinic Acid (CBDOA) Cannabidivarinic Acid (CBDVA) (30245 | 9001575) OHO OH ORCINOL SERIES HO VARINOL SERIES Orcinolic phytocannabinoids have been identified Olivetolic Acid Varinolic cannabinoids were once rare but are now H OH (26282) OH H H O O H in Nepalese and Brazilian samples but are also found OH targets of selective breeding. They have also been H H as major compounds in non-Cannabis species O O O O O exhibited in higher abundance in C. indica over C. sativa. such as Rhododendron. Cannabicyclorcinol (CBLO) Cannabicitraorcin (CBTO) (citran) Cannabicitravarin (CBTV) (citran) Cannabicyclovarin (CBLV) O OH Cannabielsovarin (CBEV) CoA-S OH Hexanoyl-CoA OH OH OH OH O OH OH O OH HO OH OH HO Cannabigerorcin (CBGO) (E isomer) Cannabigerovarin (CBGV) (E isomer) OH O O OH (23257) O O O O (29117 | 9002437) 9 9 Δ9-Tetrahydrocannabivarin (THCV) (Δ9-THCV) Δ -Tetrahydrocannabiorcin (THCO) (Δ -THCO) Cannabinerorcin (CBNRO) (Z isomer) Cannabinerovarin (CBNRV) (Z isomer) Cannabichromeorcinic Acid (CBCOA) Cannabichromeorcin (CBCO) (CBCV) Cannabichromevarinic Acid (CBCVA) (18091) (21742) (21974) O O exo-Tetrahydrocannabiorcin (exo-THCO) exo-Tetrahydrocannabivarin (exo-THCV)

HO HO Polyketide OH OH OH OH synthase HOHO HO OH OH OH O O OH OH OH O O OH OHO O O O OH Solid Materials Certified Solutions OH HO OH Geranyl- OH HO Geranyl- HO CoA-S S-CoA O O HO HO OH OH O O O transferase Ethanoyl-CoA Butanoyl-CoA transferase O Cannabiripsorcinol (CBRO) Cannabitriorcinol (CBTO) (triol) Cannabigerorcinic Acid (CBGOA) (E isomer) Varinolic Acid Cannabigerovarinic Acid (CBGVA) (E isomer) Cannabitrivarinol (CBTV) (triol) Cannabiripsovarinol (CBRV) Δ9-Tetrahydrocannabiorcinic Acid (Δ9-THCOA) Orcinolic Acid Tetrahydrocannabivarinic Acid (Δ9-THCVA) (23258) OO (26283) (29787 | 25469) Cannabinerorcinic Acid (CBNROA) (Z isomer) 3 x Cannabinerovarinic Acid (CBNRVA) (Z isomer) (21259) CoA-SOH

OH O OH OH OH O OH OH OH HO O O O O O O 8 8 Δ8-Tetrahydrocannabivarin (Δ8-THCV) Cannabinorcin (CBO) Cannabinorcinic Acid (CBOA) Δ -Tetrahydrocannabiorcin (Δ -THCO) © 2018 Cayman Chemical Cannabivarinic Acid (CBVA) (CBV) Item No. Product Name Item No. Product Name Revised September 2020 (27322) (21664)

9002438 (±)-Cannabicyclol ISO60163 (±)-Cannabichromene (CRM)*

90080 Cannabidiol 18090 Cannabidiolic Acid (CRM)

9001574 Cannabidivarin 23251 Phytocannabinoid Mixture 3 (CRM)

9001575 Cannabidivarinic Acid 25077 Phytocannabinoid Mixture 6 (CRM)

15293 Cannabigerol 21305 Phytocannabinoid Mixture 10 (CRM)

9001572 Cannabigerolic Acid 21306 Phytocannabinoid Mixture 11 (CRM) (1 ml, 250 µg/ml)

9002437 Cannabigerovarin 18091 Tetrahydrocannabivarin (CRM)

25469 Cannabigerovarinic Acid ISO60158 Δ8-THC (CRM)*

25495 Cannabinol ISO60157 Δ9-THC (CRM)*

29031 CBDB ISO60175 THCA-A (CRM)

View additional phytocannabinoidsOH at www.caymanchem.comOH *Isotopically labeled versions of these standards are available for mass spec analysis 4 4

O HO DiscoverCBDB Our Latest PhytocannabinoidΔ9-THCB News

OH OH 5 5 O PPARα/δ/γ HO CB₁ GPR18 TRPV1-4 CB₂ GPR55 TRPM8 CBD Δ9-THC GPR119 TRPA1 Why Does Alkyl Chain Length Matter? ​Cannabis: Our Key to the EndocannabinoidGene transcription System www.caymanchem.com/alkylchainOH OH 7 7 www.caymanchem.com/cannabiskey O HO CBDP Δ9-THCP

WWW.CAYMANCHEM.COM CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 2021 Cayman offers the world’s largest collection of potent cannabinoid receptor agonists, antagonists, and inverse agonists, many of which are highly selective for either the central or peripheral receptor.

CB1-Selective Ligands Item No. Product Name Summary

71670 AM251 CB1 receptor antagonist (Kis = 7.5 and 2,290 nM for CB1 and CB2, respectively)

91054 Arachidonoyl 2’-Chloroethylamide CB1 receptor agonist (Kis = 1.4 and >2,000 nM for CB1 and CB2, respectively)

90070 R-1 Methanandamide CB1 receptor agonist (Kis = 17.9-28.3 and 815-868 nM for CB1 and CB2, respectively)

10004184 NESS 0327 CB1 receptor antagonist (Kis = 0.35 pM and 21 nM for CB1 and CB2, respectively)

9000484 Rimonabant CB1 receptor antagonist (Kis = 5.6 and >1,000 nM for CB1 and CB2, respectively)

CB2-Selective Ligands Item No. Product Name Summary

10006974 AM630 CB2 receptor inverse agonist (Kis = 5,152 and 31.2 nM for CB1 and CB2, respectively)

10010118 AM1241 CB2 receptor agonist (Kis = 580 and 7.1 nM for CB1 and CB2, respectively)

10005428 JWH 133 CB2 receptor agonist (Kis = 677 and 3.4 nM for CB1 and CB2, respectively)

10009280 L-759,633 CB2 receptor agonist (Kis = 1,043 and 6.4 nM for CB1 and CB2, respectively)

9000491 SR 144528 CB2 receptor inverse agonist (Kis = 305 and 0.3 nM for CB1 and CB2, respectively)

Mixed CB1/CB2-Selective Ligands Item No. Product Name Summary

90084 (−)-CP 55,940 CB receptor agonist (Kis = 0.5-5 and 0.69-2.8 nM for CB1 and CB2, respectively)

90083 HU-210 (exempt preparation) CB receptor agonist (Kis = 0.73 and 0.524 nM for CB1 and CB2, respectively)

10009023 (+)-WIN 55,212-2 (mesylate) CB receptor agonist (Kis = 62.3 and 3.3 nM for CB1 and CB2, respectively) Over 700 synthetic cannabinoids including parent compounds, isomers, labeled standards, and metabolites are available at www.caymanchem.com

Cannabinoid-Related Receptor: GPR55

The GPR55 receptor is a (non-CB1/CB2) receptor that displays high binding affinity to many cannabinoid ligands. Cayman carries select ligands specific to this receptor as well as an antibody to study its role in cannabinoid-related signal transduction.

Item No. Product Name Summary

10224 GPR55 Polyclonal Antibody Host: Rabbit • Species Reactivity: (+) Human, bovine • Applications: ELISA, WB

10004259 A selective GPR55 agonist (EC50s = 2.5, >30, and >30 μM for GPR55, CB1, and CB2, respectively) A potent and selective CB and GPR55 agonist (EC s = 10, 37, and >30,000 nM for CB , 62165 2-Arachidonyl Glycerol ether 1 50 1 GPR55, and CB2, respectively)

15247 CID16020046 A selective GPR55 inverse agonist (IC50 = 15 µM)

17641 ML-184 A potent and synthetic agonist of GPR55 (EC50 = 0.26 µM)

15184 ML-193 A potent and selective GPR55 antagonist (IC50 = 221 nM) A potent and selective GPR55 agonist (EC s = 13, >30,000, and >30,000 nM for GPR55, CB , 10006803 O-1602 50 1 and CB2, respectively)

Find more research tools at our Cannabinoid Resource Center at www.caymanchem.com/cannabinoids

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