ML-00253764 is a non-peptide melanocortin receptor 4 (MC4R) antagonist (inhibitor) with Ki and IC50s of 0.16 µM and 0.103 µM, respectively. Brain Penetrant.

Physicochemical Properties

Molecular Formula	C18H19BRCLFN2O
Molecular Weight	413.711666345596
Exact Mass	412.035
CAS #	1706524-94-8
Related CAS #	ML00253764;681847-92-7
PubChem CID	90488979
Appearance	Off-white to light yellow solid powder
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	5
Heavy Atom Count	24
Complexity	420
Defined Atom Stereocenter Count	0
SMILES	C(C1C(=CC=CC=1C1=NCCN1)F)CC1C=C(Br)C=CC=1OC.Cl
InChi Key	KZUMGPQDDCBFBF-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H18BrFN2O.ClH/c1-23-17-8-6-13(19)11-12(17)5-7-14-15(3-2-4-16(14)20)18-21-9-10-22-18;/h2-4,6,8,11H,5,7,9-10H2,1H3,(H,21,22);1H
Chemical Name	2-[2-[2-(5-bromo-2-methoxyphenyl)ethyl]-3-fluorophenyl]-4,5-dihydro-1H-imidazole;hydrochloride
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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

Targets	MC4R
ln Vitro	With a mean IC50 of 0.32 μM, 0.81 μM, and 2.12 μM for hMC4-R, hMC3-R, and hMC5-R, respectively, ML-00253764 displaces NDP-α-MSH binding[1]. In HEK293 cell membranes expressing MC4R, ML-00253764 (100 μM) reduces cAMP synthesis by 20% when triggered by [NLE4,D-Phe7]-α-melanocyte stimulating hormone ([NDP]-α-MSH); however, it had no effect on cAMP levels in membranes expressing MC3R or MC5R[1].
ln Vivo	Chronic peripheral dose of ML-00253764 (subcutaneous injection; 3, 10, or 30 mg/kg; once daily) protects against tumor-induced body weight loss in BALB/c mice harboring CT-26 tumors[1]. Polyethylene glycol 200/saline (1:10) dissolves ML-00253764 in a volume of 10 mL/kg (For reference only)[1].
Animal Protocol	Animal/Disease Models: CT-26 tumor bearing BALB/c mice[1] Doses: 3, 10 , or 30 mg/kg Route of Administration: subcutaneous (sc) injection; 3, 10, or 30 mg/kg; one time/day Experimental Results: decreased tumor-induced weight loss in a mouse model.
References	[1]. Identification of 2-[2-[2-(5-bromo-2- methoxyphenyl)-ethyl]-3-fluorophenyl]-4,5-dihydro-1H-imidazole (ML00253764), a small molecule melanocortin 4 receptor antagonist that effectively reduces tumor-induced weight loss in a mouse model. J Med Chem. 2004 Mar 25;47(7):1602-4.

Solubility Data

Solubility (In Vitro)

DMSO: 12.5 mg/mL (30.21 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (3.02 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 12.5 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: ≥ 1.25 mg/mL (3.02 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 12.5 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: ≥ 1.25 mg/mL (3.02 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 12.5 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	2.4172 mL	12.0858 mL	24.1715 mL
	5 mM	0.4834 mL	2.4172 mL	4.8343 mL
	10 mM	0.2417 mL	1.2086 mL	2.4172 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.