CMPD101 is a novel, potent and selective inhibitor of G-protein coupled receptor kinase 2 and 3 (GRK2/GRK3) with IC50 values of 35 and 32 nM for GRK2 and GRK3, respectively. CMPD101 exhibits selectivity for GRK2/3 over GRK1/5 and reduces DAMGO-induced desensitization and internalization of μ-opioid receptors. CMPD101 has been shown to potentiate phosphatidylinositol 4,5-bisphosphate (PIP2) depletion and slow agonist-induced desensitization of protease-activated receptor 2 (PAR2).

Physicochemical Properties

Molecular Formula	C24H21F3N6O
Molecular Weight	466.458354711533
Exact Mass	466.172
Elemental Analysis	C, 61.80; H, 4.54; F, 12.22; N, 18.02; O, 3.43
CAS #	865608-11-3
PubChem CID	11677079
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Index of Refraction	1.622
LogP	3.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	34
Complexity	659
Defined Atom Stereocenter Count	0
SMILES	O=C(C1C=C(NCC2N(C)C(C3C=CN=CC=3)=NN=2)C=CC=1)NCC1C(C(F)(F)F)=CC=CC=1
InChi Key	WFOVEDJTASPCIR-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H21F3N6O/c1-33-21(31-32-22(33)16-9-11-28-12-10-16)15-29-19-7-4-6-17(13-19)23(34)30-14-18-5-2-3-8-20(18)24(25,26)27/h2-13,29H,14-15H2,1H3,(H,30,34)
Chemical Name	3-[[[4-Methyl-5-(4-pyridinyl)-4H-1,2,4-triazol-3-yl]methyl]amino]-N-[[2-(trifluoromethyl)phenyl]methyl]benzamide
Synonyms	Takeda101; CMPD101; Takeda-101; Takeda 101; CMPD 101; CMPD-101.
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	The HEK-B2 cell line's plasma membrane retains the β2AR-GFP protein fusion while CMPD101 (100 μM; first 20 min) inhibits the internalization of β2AR and significantly lowers the formation of protein-coated vesicles induced by isopropanol inducer. CMPD101 (3-30 μM; first 30 min) produces strong Ser375 phosphorylation, which is partially inhibited by 3 μM Cmpd101 for 30 min. 30 μM Cmpd101 totally replenishes cell death. 1]. prevents MOPr from being phosphorylated on the residues of Thr370, Thr376, and Thr379 [2]. CMPD101 (3-30 μM; 30 min ago) elicits baseline ERK1/2 phosphorylation in HEK 293 cells expressing HA-MOPrs Already added, however DAMGO-induced ERK1/2 and Elk-1 activation is unaffected by the compound[2].
Cell Assay	Western Blot Analysis[2] Cell Types: HEK 293 cells stably expressing HA-tagged rat MOPr Tested Concentrations: 3 μM, 30 μM Incubation Duration: 30 minutes ago Experimental Results: No effect on DAMGO-induced p-ERK1/2 and p- Elk-1 expression.
References	[1]. Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure. J Med Chem. 2017 Aug 24;60(16):6942-6990. [2]. Inhibition of prostatic smooth muscle contraction by the inhibitor of G protein-coupled receptor kinase 2/3, CMPD101.Eur J Pharmacol. 2018 Jul 15;831:9-19.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~535.95 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.46 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 (4.46 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.46 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	2.1438 mL	10.7190 mL	21.4381 mL
	5 mM	0.4288 mL	2.1438 mL	4.2876 mL
	10 mM	0.2144 mL	1.0719 mL	2.1438 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.