CAS NO: | 1467057-23-3 |
规格: | ≥98% |
包装 | 价格(元) |
5mg | 电议 |
10mg | 电议 |
25mg | 电议 |
50mg | 电议 |
100mg | 电议 |
250mg | 电议 |
500mg | 电议 |
Molecular Weight (MW) | 341.79 |
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Formula | C19H16ClNO3 |
CAS No. | 1467057-23-3 |
Storage | -20℃ for 3 years in powder form |
-80℃ for 2 years in solvent | |
Solubility (In vitro) | DMSO: ~68 mg/mL (199 mM) |
Water: <1 mg/mL | |
Ethanol: ~68 mg/mL (199 mM) | |
Other info | Chemical Name: 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic acid InChi Key: FHQXLWCFSUSXBF-UHFFFAOYSA-N InChi Code: InChI=1S/C19H16ClNO3/c20-16-9-17-14(15(10-21-17)18(22)23)8-13(16)11-2-4-12(5-3-11)19(24)6-1-7-19/h2-5,8-10,21,24H,1,6-7H2,(H,22,23) |
Synonyms | PF-06409577; PF-6409577; PF 06409577; PF6409577; PF06409577; PF 6409577 |
SMILES Code | O=C(C1=CNC2=C1C=C(C3=CC=C(C4(O)CCC4)C=C3)C(Cl)=C2)O |
In Vitro | In vitro activity: PF-06409577 activates AMPK α1β1γ1 and α2β1γ1 isoforms with EC50 of 7.0 nM and 6.8 nM but was much less active against α1β2γ1/α2β2γ1/α2β2γ3 AMPK isoforms with EC50 greater 4000 nM Kinase Assay: PF-06409577 is prepared in DMSO. PF-06409577 is incubated with fully phosphorylated AMPK in assay buffer at room temperature for 15 min followed by addition of PP2a and another incubation for 60 min at room temperature. The phosphatase treatment is quenched and the kinase assay initiated with the addition of okadaic acid (50 nM final), 50 nM Cy-5 SAMS peptide and ATP equal to Km for each isoform. Reactions are incubated for an additional 60 min and the kinase reaction is quenched with the addition of 10 mM EDTA and 2 nM Eu-pACC antibody in detection Buffer. Kinase activity is monitored by excitation at 320 nM and measuring emission at 665 and 615 nM, respectively. Cell Assay: PF-06409577 possesses similar potency toward the human and rat α1β1γ1 isoforms. In broad panel screening against other receptors, channels, PDEs and kinases, PF-06409577 exhibits minimal off-target pharmacology. PF-06409577 shows no detectable inhibition of hERG in a patch-clamp assay (100 μM) and is not an inhibitor (IC50>100 μM) of the microsomal activities of major human cytochrome P450 isoforms. |
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In Vivo | PF-06409577 has moderate plasma clearance in rats, dogs, and monkeys, and is well distributed with steady state distribution volume. Following oral administration of crystalline PF-06409577 in 0.5% methylcellulose suspension, PF-06409577 is rapidly absorbed in rats, dogs, and monkeys. The corresponding oral bioavailability values in rats, dogs, and monkeys, are 15%, 100%, and 59%, respectively. Dose responsive increases in pAMPK relative to total AMPK (tAMPK) in whole kidney tissue are observed with a maximal 3.8-fold response at 300 mg/kg PF-06409577 treatment. Oral administration of PF-06409577 (10, 30, and 100 mg/kg QD) results in dose-dependent reductions in proteinuria in the obese ZSF1 animals, with greater than 2-fold reduction in 24-hour urinary albumin loss compared to vehicle control after 60 days of treatment. |
Animal model | ZSF-1 rats |
Formulation & Dosage | 5% Vitamin E TPGS in water |
References | J Med Chem. 2016 Sep 8;59(17):8068-81; J Pharmacol Exp Ther. 2017 May;361(2):303-311. |