THIQ is a novel and potent agonist of the melanocortin-4 receptor (MC4R) with high activity for hMC4R (IC50=1.2 nM, EC50=2.1 nM) and rMC4R (IC50=0.6 nM, EC50=2.9 nM).
Physicochemical Properties
| Molecular Formula | C33H41CLN6O2 |
| Molecular Weight | 589.1706 |
| Exact Mass | 588.298 |
| CAS # | 312637-48-2 |
| PubChem CID | 9938402 |
| Appearance | White to off-white solid powder |
| LogP | 5.22 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 42 |
| Complexity | 899 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | C1CCC(CC1)C2(CCN(CC2)C(=O)[C@@H](CC3=CC=C(C=C3)Cl)NC(=O)[C@H]4CC5=CC=CC=C5CN4)CN6C=NC=N6 |
| InChi Key | HLCHESOMJVGDSJ-LOYHVIPDSA-N |
| InChi Code | InChI=1S/C33H41ClN6O2/c34-28-12-10-24(11-13-28)18-30(38-31(41)29-19-25-6-4-5-7-26(25)20-36-29)32(42)39-16-14-33(15-17-39,21-40-23-35-22-37-40)27-8-2-1-3-9-27/h4-7,10-13,22-23,27,29-30,36H,1-3,8-9,14-21H2,(H,38,41)/t29-,30-/m1/s1 |
| Chemical Name | (3R)-N-[(2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1,2,4-triazol-1-ylmethyl)piperidin-1-yl]-1-oxopropan-2-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide |
| 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 | THIQ has poor potency against the human MC1R, MC3R, and MC5R, with IC50s of 2067, 761, and 326 nM and EC50s of 2850, 2487, and 737 nM, respectively. THIQ has poor potency in rat MC3R and MC5R, with IC50s of 1883 and 1575 nM, and EC50s of 1325 and >3000 nM [1]. THIQ (10 μM; 24 hours) reduces the signal intensity of WT MC4R by about 50%, while boosting the signal intensity of three mutants (N62S, C84R, and C271Y) in HEK293 cells [2]. |
| ln Vivo | In sexually mature male Sprague Dawley rats, THIQ (0.3-10 mg/kg; iv) dose-dependently induces erections (ED50=0.87 mg/kg). At 5 mg/kg, there was the greatest rise in erections (60%) but there was no discernible difference between that and 1 mg/kg. With an average rise of 31±4%, THIQ (20 mg/kg; oral) also considerably improves erectile response [1]. When given at 1 mg/kg IV and 10 mg/kg PO, THIQ therapy in Sprague-Dawley rats resulted in a t1/2 of 0.6 hours [1]. |
| References |
[1]. Design and pharmacology of N-[(3R)-1,2,3,4-tetrahydroisoquinolinium- 3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl)- 2-[4-cyclohexyl-4-(1H-1,2,4-triazol- 1-ylmethyl)piperidin-1-yl]-2-oxoethylamine (1), a potent, selective, melanocortin subtype-4 receptor agonist. J Med Chem. 2002 Oct 10;45(21):4589-93. [2]. A small molecule agonist THIQ as a novel pharmacoperone for intracellularly retainedmelanocortin-4 receptor mutants. Int J Biol Sci. 2014 Jul 20;10(8):817-24. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~250 mg/mL (~424.33 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.53 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 (3.53 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 | 1.6973 mL | 8.4865 mL | 16.9730 mL | |
| 5 mM | 0.3395 mL | 1.6973 mL | 3.3946 mL | |
| 10 mM | 0.1697 mL | 0.8487 mL | 1.6973 mL |