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| Targets |
The primary molecular target of SNT-207858 free base is the melanocortin-4 receptor (MC-4 receptor; MC4R), a G protein-coupled receptor predominantly expressed in the central nervous system. MC4R plays a critical role in the regulation of food intake, energy expenditure, and body weight. SNT-207858 acts as a potent antagonist at this receptor, blocking the binding of endogenous melanocortin peptides such as alpha-melanocyte-stimulating hormone (alpha-MSH). It exhibits high selectivity for MC4R over other melanocortin receptor subtypes, with a 170-fold selectivity versus MC-3 receptor and a 40-fold selectivity versus MC-5 receptor.
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| ln Vitro |
SNT207858 has a 22 nM affinity for the MC-4 receptor and a selectivity that is 170 times greater than that of MC-3 and 40 times greater than that of MC-5 [1].
In vitro studies demonstrate that SNT-207858 binds to the MC-4 receptor with high affinity, exhibiting an IC50 of 22 nM in binding assays. Functional assays further confirm its potent antagonistic activity, with an IC50 of 11 nM for inhibition of MC-4 receptor-mediated function. The compound shows significant selectivity for MC4R, being 170-fold more selective for MC4R compared to MC-3 receptor and 40-fold more selective compared to MC-5 receptor. These in vitro characteristics establish SNT-207858 as a highly potent and selective tool compound for studying MC4R biology in cellular systems. |
| ln Vivo |
Tumor-induced weight loss in mice is considerably lessened by SNT207858 (30 mg/kg; oral; once daily; 15 days) [1].
In vivo, SNT-207858 free base demonstrates oral bioavailability and blood-brain barrier penetration, enabling central nervous system target engagement. In a mouse model of C26 adenocarcinoma-induced cachexia, oral administration of SNT-207858 at 30 mg/kg once daily for 15 days significantly reduced tumor-induced weight loss. Additionally, at a dose of 20 mg/kg, the compound increases light phase food intake in mice. In the same cachexia model, treatment with 30 mg/kg per day prevented decreases in body weight, lean mass, and fat mass, demonstrating its potential to counteract cancer-associated wasting. |
| Enzyme Assay |
The in vitro binding affinity of SNT-207858 for the MC-4 receptor is typically assessed using radioligand competition binding assays. Membrane preparations from cells expressing recombinant human MC4R are incubated with a radiolabeled MC4R ligand (e.g., [125I]-NDP-alpha-MSH) in the presence of varying concentrations of SNT-207858. After incubation at room temperature for a specified period, the reaction mixture is filtered through glass fiber filters to separate bound from free radioligand. Filter-bound radioactivity is measured by scintillation counting, and IC50 values are calculated by nonlinear regression analysis of competition curves. Non-specific binding is determined in the presence of an excess of unlabeled ligand.
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| Cell Assay |
In vitro cellular functional assays typically employ cell lines engineered to stably express the human MC-4 receptor along with a cAMP-responsive reporter system. Cells are seeded in multi-well plates and pre-incubated with culture medium. Following serum starvation, cells are treated with serial dilutions of SNT-207858 in the presence of an MC4R agonist (such as NDP-alpha-MSH) that stimulates cAMP production. After incubation at 37degC in a CO2 incubator, intracellular cAMP levels are measured using a homogeneous time-resolved fluorescence (HTRF) or luminescence-based cAMP detection kit. The IC50 for antagonism is determined by fitting the inhibition curves using a four-parameter logistic model.
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| Animal Protocol |
Animal/Disease Models: C26 adenocarcinoma cachexia model mouse [1]
Doses: 30 mg/kg Route of Administration: po (po (oral gavage)) one time/day; 15 days Experimental Results: Dramatically diminished tumor-induced weight loss. In vivo efficacy studies are conducted using established animal models. A commonly used model is the C26 murine colon carcinoma-induced cachexia model, where immunocompetent mice are inoculated subcutaneously with C26 adenocarcinoma cells. After tumor establishment (typically 7-10 days post-inoculation), mice are randomized into treatment groups. SNT-207858 is administered orally at doses ranging from 10 to 30 mg/kg, once daily for up to 15 days. Body weight, food intake, lean mass, and fat mass are monitored throughout the study. At study termination, tumors are excised and weighed, and plasma/tissue samples are collected for pharmacokinetic and biomarker analysis. Efficacy is evaluated by comparing body weight changes and cachexia parameters between treated and vehicle-control groups. |
| ADME/Pharmacokinetics |
SNT-207858 free base is orally bioavailable and capable of penetrating the blood-brain barrier, properties essential for its central MC4R-targeting activity. As a small molecule with a molecular weight of 616.62 g/mol, it is formulated for oral administration in vivo using vehicles such as 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline. The compound is soluble in DMSO at concentrations up to 125 mg/mL (202.72 mM). While specific pharmacokinetic parameters such as half-life, Cmax, AUC, and bioavailability have not been extensively detailed in publicly available sources, its oral activity and CNS penetration are well-established through functional in vivo efficacy studies.
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| Toxicity/Toxicokinetics |
Available toxicological information for SNT-207858 free base is limited to standard laboratory safety handling guidelines. The compound is classified for research use only and is not intended for human therapeutic or diagnostic applications. Under fire conditions, the compound may decompose and emit toxic fumes. Standard laboratory precautions should be observed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated fume hood. Runoff from fire control or dilution water may cause environmental pollution, and release into the environment should be avoided. The compound is not classified as a hazardous material for transportation purposes. Long-term storage is recommended in a cool, dry place at -20degC.
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| References | |
| Additional Infomation |
SNT-207858 free base (CAS#: 1104662-66-9) is a research compound supplied for laboratory use only, not for therapeutic or diagnostic applications. It is a non-peptide, small-molecule antagonist of the melanocortin-4 receptor with oral activity and blood-brain barrier penetration. The molecular formula is C32H43Cl2N5O3 with a molecular weight of 616.62. The compound is available with purity ≥95% to ≥99%. The mechanism of action involves competitive antagonism at the MC4R, blocking the anorexigenic signaling mediated by endogenous melanocortin peptides. This pharmacological profile positions SNT-207858 as a valuable tool for investigating MC4R biology, appetite regulation, and cachexia. As of the current date, SNT-207858 remains a preclinical research compound and has not been approved for clinical use or received regulatory approval for any therapeutic indication.
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| Molecular Formula |
C32H43CL2N5O3
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| Molecular Weight |
616.6215
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| Exact Mass |
615.274
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| CAS # |
1104662-66-9
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| Related CAS # |
SNT-207858;1104080-42-3
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| PubChem CID |
42630200
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| Appearance |
White to off-white solid powder
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| LogP |
5.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
42
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| Complexity |
863
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1C([H])=C(C([H])=C([H])C=1C([H])([H])[C@]([H])(C(N1C([H])([H])C([H])([H])C([H])(C2=C(C([H])=C([H])C([H])=N2)OC([H])([H])[C@@]([H])(C([H])([H])C([H])([H])[H])N2C([H])([H])C([H])([H])C([H])([H])C2([H])[H])C([H])([H])C1([H])[H])=O)N([H])C(N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H])=O)Cl
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| InChi Key |
GNSVFEJLUPMLCZ-IXCJQBJRSA-N
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| InChi Code |
InChI=1S/C32H43Cl2N5O3/c1-2-26(37-14-3-4-15-37)22-42-29-8-7-13-35-30(29)23-11-18-38(19-12-23)31(40)28(36-32(41)39-16-5-6-17-39)20-24-9-10-25(33)21-27(24)34/h7-10,13,21,23,26,28H,2-6,11-12,14-20,22H2,1H3,(H,36,41)/t26-,28-/m1/s1
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| Chemical Name |
N-[(2R)-3-(2,4-dichlorophenyl)-1-oxo-1-[4-[3-[(2R)-2-pyrrolidin-1-ylbutoxy]pyridin-2-yl]piperidin-1-yl]propan-2-yl]pyrrolidine-1-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 : ~100 mg/mL (~162.17 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.37 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 (3.37 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 | 1.6217 mL | 8.1087 mL | 16.2174 mL | |
| 5 mM | 0.3243 mL | 1.6217 mL | 3.2435 mL | |
| 10 mM | 0.1622 mL | 0.8109 mL | 1.6217 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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