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| 5mg |
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| Targets |
THIQ primarily targets the melanocortin-4 receptor (MC4R), a G protein-coupled receptor involved in the regulation of energy homeostasis, feeding behavior, and sexual function. It acts as a selective agonist with high affinity and potency for hMC4R (IC50 = 1.2 nM, EC50 = 2.1 nM) and rMC4R (IC50 = 0.6 nM, EC50 = 2.9 nM). THIQ maintains low potency at MC1R (IC50 = 2067 nM), MC3R (IC50 = 761 nM), and MC5R (IC50 = 326 nM), demonstrating selectivity for MC4R.
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| 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].
In vitro, THIQ functions as a selective MC4R agonist with high affinity and potency for hMC4R (IC50 = 1.2 nM, EC50 = 2.1 nM) and rMC4R (IC50 = 0.6 nM, EC50 = 2.9 nM). It maintains low potency at MC1R, MC3R, and MC5R. THIQ acts as a pharmacoperone of the MC4R, rescuing the cell surface expression and signaling of some intracellularly retained MC4R mutants. In HEK293 cells, 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). |
| 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].
In vivo, THIQ plays a role in eliciting erectile activity in rodents. In sexually mature male Sprague Dawley rats, THIQ (0.3-10 mg/kg; intravenous) dose-dependently induces erections with an ED50 of 0.87 mg/kg. At 5 mg/kg, there was the greatest rise in erections (60%). THIQ (20 mg/kg; oral) also considerably improves erectile response with an average rise of 31±4%. When given at 1 mg/kg IV and 10 mg/kg PO, THIQ treatment in Sprague-Dawley rats resulted in a t1/2 of 0.6 hours. |
| Enzyme Assay |
The cell-free assay for THIQ involves evaluating its binding affinity to MC4R. Radioligand binding assays are performed using membrane preparations from cells expressing recombinant human or rat MC4R. THIQ is incubated with membranes and a radiolabeled MC4R ligand. Competition binding experiments determine IC50 values (1.2 nM for hMC4R, 0.6 nM for rMC4R). Selectivity is assessed by testing against MC1R, MC3R, and MC5R.
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| Cell Assay |
For in vitro cellular assays, THIQ is typically dissolved in DMSO and diluted in cell culture medium. HEK293 cells expressing MC4R or other melanocortin receptors are treated with various concentrations of THIQ. Functional assays such as cAMP accumulation are used to measure receptor activation. EC50 values (2.1 nM for hMC4R, 2.9 nM for rMC4R) are determined from dose-response curves. The compound's ability to rescue mutant MC4R expression and signaling is assessed in cells expressing MC4R mutants.
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| Animal Protocol |
In vivo animal studies for THIQ are conducted in sexually mature male Sprague Dawley rats. The compound is administered via intravenous injection (0.3-10 mg/kg) or oral gavage (20 mg/kg). Erectile responses are measured and quantified. Pharmacokinetic parameters are determined from plasma samples collected at various time points. Efficacy is evaluated by comparing erectile responses between treatment and control groups. The compound's effects on feeding behavior and energy homeostasis can also be assessed.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of THIQ include a molecular weight of 589.17 g/mol and molecular formula C33H41ClN6O2. The compound has a purity of ≥98%. When given at 1 mg/kg IV and 10 mg/kg PO in Sprague-Dawley rats, THIQ resulted in a t1/2 of 0.6 hours. The compound is typically stored at appropriate conditions as a research reagent. Detailed ADME parameters such as Cmax and AUC are not extensively reported in the available literature.
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| Toxicity/Toxicokinetics |
The toxicity profile of THIQ has not been extensively characterized in published literature. As an MC4R agonist, potential toxicities may include effects on energy homeostasis and cardiovascular function. Standard toxicology studies would include acute and sub-chronic toxicity assessments in rodent models. The compound is intended for research use only and not for therapeutic applications in humans. Standard safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
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). It is the first selective MC4R agonist and maintains low potency at MC1R, MC3R, and MC5R. THIQ acts as a pharmacoperone rescuing MC4R mutants and elicits erectile activity in rodents. THIQ is a research tool for studying MC4R function and has not entered clinical trials.
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| Molecular Formula |
C33H41CLN6O2
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| Molecular Weight |
589.1706
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| Exact Mass |
588.298
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| CAS # |
312637-48-2
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| PubChem CID |
9938402
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| Appearance |
White to off-white solid powder
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| LogP |
5.22
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
42
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| Complexity |
899
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| Defined Atom Stereocenter Count |
2
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| 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
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| InChi Key |
HLCHESOMJVGDSJ-LOYHVIPDSA-N
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| 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
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| 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
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~424.33 mM)
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| 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 |
*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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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