| Size | Price | |
|---|---|---|
| 10mg |
Purity: ≥98%
PF-00446687 is a novel, potent, highly selective, brain penetrant small-molecule MC4R (melanocortin-4 receptor) agonist with EC50 of 12 ± 1 nM. The role of the MC4 receptor subtype has received particular scrutiny, but the sufficiency of its selective activation in potentiating sexual response has remained uncertain owing to conflicting data from studies in preclinical species. We describe here the discovery of a novel series of small-molecule MC4 receptor agonists derived from library hit 2. The addition of methyl substituents at C3 and C5 of the 4-phenylpiperidin-4-ol ring was found to be markedly potency-enhancing, enabling the combination of low nanomolar potencies with full rule-of-five compliance. In general, the series shows only micromolar activity at other melanocortin receptors.
| ln Vitro |
PF-00446687 has a Ki of 27±4 nM when binding MC4 receptors. PF-00446687 exhibits comparatively low activity on MC1, MC3, and MC5 receptors, as evidenced by its respective EC50 values of 1.02±0.30 μM, 1.16±0.35 μM, and 1.98±0.20 μM. The CEREP Bioprint Broad Ligand Screening Panel was used to assess the broad off-target profile of PF-00446687. The results showed that the compound had the strongest binding activity at sodium channels (Ki=690 nM), muscarinic M2 receptors (Ki=730 nM), and sigma receptors (Ki=330 nM)[1].
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| ln Vivo |
Pf-446687 is stable in vivo, brain-penetrating, and very selective for MC4R. In prairie voles, peripheral treatment of the highly selective small molecule MC4R agonist Pf-446687 and the brain-penetrating MC3/4R receptor peptide agonist Melanotan II (MTII) promotes partner preference development, but not in non-monogamous meadow voles. It does not contain a [2].
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| References |
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| Molecular Formula |
C28H36N2O2F2.HCL
|
|---|---|
| Molecular Weight |
507.05538
|
| Exact Mass |
506.251
|
| CAS # |
862282-10-8
|
| Related CAS # |
862281-92-3
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| PubChem CID |
49861348
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| Appearance |
White to off-white solid powder
|
| LogP |
5.458
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
35
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| Complexity |
708
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| Defined Atom Stereocenter Count |
4
|
| SMILES |
C[C@@H]1CN(C[C@@H](C1(C2=CC=CC=C2)O)C)C(=O)[C@@H]3CN(C[C@H]3C4=C(C=C(C=C4)F)F)C(C)(C)C.Cl
|
| InChi Key |
WWCBDWDDPAPGHX-UZEFPFOTSA-N
|
| InChi Code |
InChI=1S/C28H36F2N2O2.ClH/c1-18-14-31(15-19(2)28(18,34)20-9-7-6-8-10-20)26(33)24-17-32(27(3,4)5)16-23(24)22-12-11-21(29)13-25(22)30;/h6-13,18-19,23-24,34H,14-17H2,1-5H3;1H/t18-,19+,23-,24+,28-;/m0./s1
|
| Chemical Name |
((3S,4R)-1-(tert-Butyl)-4-(2,4-difluorophenyl)pyrrolidin-3-yl)((3R,4R,5S)-4-hydroxy-3,5-dimethyl-4-phenylpiperidin-1-yl)methanone Hydrochloride
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| Synonyms |
PF-00446687 HCl; PF 446687 hydrochloride; PF446687; PF-446687
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9722 mL | 9.8608 mL | 19.7215 mL | |
| 5 mM | 0.3944 mL | 1.9722 mL | 3.9443 mL | |
| 10 mM | 0.1972 mL | 0.9861 mL | 1.9722 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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