CB1-IN-1 (also known as DBPR211) is a novel, potent, peripherally restricted antagonist of the CB1R (cannabinoid 1 receptor) with Ki values of 0.3 nM and 21 nM for CB1R (EC50 of 3 nM) and CB2R, respectively. CB1-IN-1 has demonstrated notable effects on weight loss and can reduce insulin resistance and hepatic steatosis in a diet-induced obese mice modea model of diet-induced obesity in mice. It therefore has a great deal of potential for use in metabolic syndromes related to obesity. Additionally, it has favorable PK profiles, such as a very low brain to plasma ratio that indicates a low likelihood of BBB crossing.

Physicochemical Properties

Molecular Formula	C33H31CL2F3N6O3S2
Molecular Weight	751.67
Exact Mass	750.122
Elemental Analysis	C, 52.73; H, 4.16; Cl, 9.43; F, 7.58; N, 11.18; O, 6.39; S, 8.53
CAS #	1429239-98-4
Related CAS #	1429239-98-4
PubChem CID	71515460
Appearance	White to off-white solid powder
Density	1.5±0.1 g/cm3
Index of Refraction	1.672
LogP	6.52
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	10
Heavy Atom Count	49
Complexity	1310
Defined Atom Stereocenter Count	0
SMILES	ClC1C=C(C=CC=1N1C(C2=CC=C(C#CC3C=CC(C(F)(F)F)=CC=3)S2)=C(C(C(NN2CCCCC2)=O)=N1)CNS(N1CCCC1)(=O)=O)Cl
InChi Key	KAIYFJUWIBTYPK-UHFFFAOYSA-N
InChi Code	InChI=1S/C33H31Cl2F3N6O3S2/c34-24-11-14-28(27(35)20-24)44-31(29-15-13-25(48-29)12-8-22-6-9-23(10-7-22)33(36,37)38)26(21-39-49(46,47)43-18-4-5-19-43)30(40-44)32(45)41-42-16-2-1-3-17-42/h6-7,9-11,13-15,20,39H,1-5,16-19,21H2,(H,41,45)
Chemical Name	1-(2,4-dichlorophenyl)-N-piperidin-1-yl-4-[(pyrrolidin-1-ylsulfonylamino)methyl]-5-[5-[2-[4-(trifluoromethyl)phenyl]ethynyl]thiophen-2-yl]pyrazole-3-carboxamide
Synonyms	DBPR 211; DBPR211; DBPR-211; CB1-IN-1; CB1-IN1; CB1 IN 1; CB1IN 1; CB1IN-1
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In vitro activity: CB1-IN-1 s a novel peripherally restricted CB1R antagonis, with Ki of 0.3 nM and 21 nM for CB1R (EC50 = 3 nM) and CB2R, respectively.
ln Vivo	CB1-IN-1 has significantly reduces body weight in mice that are fed an obesity-inducing diet.
Animal Protocol
References	[1]. Discovery of 1-(2,4-dichlorophenyl)-N-(piperidin-1-yl)-4-((pyrrolidine-1-sulfonamido)methyl)-5-(5-((4-(trifluoromethyl)phenyl)ethynyl)thiophene-2-yl)-1H-pyrazole-3-carboxamide as a novel peripherally restricted cannabinoid-1 receptor anta.

Solubility Data

Solubility (In Vitro)

DMSO: ~125 mM (~166.3 mM) Water: N/A Ethanol: N/A

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (2.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (2.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.3304 mL	6.6519 mL	13.3037 mL
	5 mM	0.2661 mL	1.3304 mL	2.6607 mL
	10 mM	0.1330 mL	0.6652 mL	1.3304 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.