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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Other Sizes |
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Purity: ≥98%
PF-06747711 (PF06747711) is a novel, potent, selective, and orally bioactive retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) inverse agonist with anti-skin inflammatory activity. It activates RORγt with an IC50 of 4.1 nM. It was identified from a high-throughput screening and displayed promising binding affinity for RORC2, inhibition of IL-17 production in Th17 cells, and selectivity against the related RORA and RORB receptor isoforms. Lead optimization to improve the potency and metabolic stability of this hit focused on two key design strategies, namely, iterative optimization driven by increasing lipophilic efficiency and structure-guided conformational restriction to achieve optimal ground state energetics and maximize receptor residence time. This approach successfully identified PF-06747711 as a potent and selective RORC2 inverse agonist, demonstrating good metabolic stability, oral bioavailability, and the ability to reduce IL-17 levels and skin inflammation in a preclinical in vivo animal model upon oral administration. Anti-skin inflammatory activity. The nuclear hormone receptor retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) is a promising target for the treatment of autoimmune diseases. A small molecule, inverse agonist of the receptor is anticipated to reduce production of IL-17, a key proinflammatory cytokine.
ln Vitro |
Compound 66, or PF-06747711, has an IC50 of 9.5 nM, which inhibits human Th17 cells' production of IL-17[1].
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ln Vivo |
In a dose-dependent way, PF-06747711 (10, 30, and 100 mg/kg, po, daily for 5 days) reduces ear edema in mice[1].
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Animal Protocol |
Animal/Disease Models: 8−10 week old female balb/c (Bagg ALBino) mouse[1]
Doses: 10, 30, and 100 mg/kg Route of Administration: PO daily over 5 days Experimental Results: Inhibited ear swelling, and caused a maximum inhibition of 46% at 100 mg/kg. |
References |
[1]. Schnute ME, et al. Discovery of 3-Cyano- N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1 H-pyrrolo[2,3- b]pyridin-5-yl)benzamide: A Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agoni
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Molecular Formula |
C26H26F3N5O2
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Molecular Weight |
497.512156009674
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CAS # |
1892576-58-7
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Related CAS # |
1892576-58-7;
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SMILES |
O=C(NC1=CN=C(N(C)C=C2C3CCN(C(C(C)C)=O)CC3)C2=C1C(F)(F)F)C4=CC=CC(C#N)=C4
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InChi Key |
BIHPJIJLDNUDGH-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C26H26F3N5O2/c1-15(2)25(36)34-9-7-17(8-10-34)19-14-33(3)23-21(19)22(26(27,28)29)20(13-31-23)32-24(35)18-6-4-5-16(11-18)12-30/h4-6,11,13-15,17H,7-10H2,1-3H3,(H,32,35)
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Chemical Name |
3-Cyano-N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide
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Synonyms |
PF06747711; PF 06747711; PF-06747711
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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 : ~41.67 mg/mL (~83.76 mM)
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0100 mL | 10.0500 mL | 20.1001 mL | |
5 mM | 0.4020 mL | 2.0100 mL | 4.0200 mL | |
10 mM | 0.2010 mL | 1.0050 mL | 2.0100 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.