PF-06409577

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

PF-06409577(PF06409577, PF 6409577) 是一种有效的、选择性的含 AMPK β1 亚型激活剂，对于 α1β1γ1 和 α2β1γ1 的 TR-FRET EC50 分别为 7.0 和 6.8 nM。

PF-06409577(PF06409577, PF 6409577)?is a potent, selective AMPK β1-containing isoforms activator with TR-FRET EC50 of 7.0 and 6.8 nM for α1β1γ1 and α2β1γ1, respectively; displays no activity for α1β2γ1/α2β2γ1/α2β2γ3 with EC50 >40 uM; elevates the phosphorylation of AMPK in the kidney, without impacting blood glucose levels, and reduces the progression of proteinuria in rat model of diabetic nephropathy.Diabetes Phase 1 Discontinued(In Vitro):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.(In Vivo):PF-06409577 demonstrates 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.

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PF 06409577 | PF06409577 | PF 6409577

Membrane Transporter/Ion Channel

AMPK

AMPKα1β1γ1

Metabolic Disease

Diabetes

1467057-23-3

341.79

C19H16ClNO3

>98% (HPLC)

DMSO: 34.2 mg/mL (100 mM); Ethanol: 6.8 mg/mL (20 mM) （ < 1 mg/ml refers to the product slightly soluble or insoluble )

O=C(C1=CNC2=C1C=C(C3=CC=C(C4(O)CCC4)C=C3)C(Cl)=C2)O

6-Chloro-5-[4-(1- hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic acid

(-20℃)

With Ice Pack

≥ 2 years