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10mg | ||
25mg | ||
50mg |
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 |
J Med Chem.2010 Apr 22;53(8):3183-97.
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Molecular Formula |
C28H36N2O2F2.HCL
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Molecular Weight |
507.05538
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CAS # |
862282-10-8
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Related CAS # |
862281-92-3
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SMILES |
O=C([C@@H]1CN(C(C)(C)C)C[C@H]1C2=CC=C(F)C=C2F)N3C[C@@H](C)[C@@](C4=CC=CC=C4)(O)[C@@H](C)C3.[H]Cl
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InChi Key |
WWCBDWDDPAPGHX-UZEFPFOTSA-N
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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
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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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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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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.