PF 6409577
PF-06409577
CAS: 1467057-23-3
Molecular Formula: C19H16ClNO3
PF 6409577 - Names and Identifiers
PF 6409577 - Physico-chemical Properties
| Molecular Formula | C19H16ClNO3 |
| Molar Mass | 341.79 |
| Density | 1.468±0.06 g/cm3(Predicted) |
| Boling Point | 610.9±55.0 °C(Predicted) |
| Solubility | Soluble in DMSO |
| Appearance | powder |
| Color | white to beige |
| pKa | 3.60±0.30(Predicted) |
| Storage Condition | room temp |
| Use | PF-06409577 is a potent and selective activator of 5′ adenosine monophosphate-activated protein kinase (AMPK) for the Potential Treatment of diabetic nephropathy. PF-06409577 has AMPK α1β1γ1 Kd=9.0 nM. AMPK α1β1γ1 EC50 = 7.0 nM; AMPK α1β2γ1 EC50 > 40000 nM. PF-06409577 showed efficacy in a preclinical model of diabetic nephropathy. Upon the basis of its potent and selective AMPK activation, low metabolic turnover in human hepatocytes, clean off-target profile, and favorable preclinical in vivo efficacy results, PF-06409577 was profiled in regulatory toxicology studies and was subsequently advanced to clinical trials to assess human pharmacokinetics and safety/ tolerability. |
| Target | AMPK α1β1γ1 |
| In vitro study | PF-06409577 can activate the subtype of AMPK Alpha 1 beta 1 Gamma 1 and Alpha 2 Beta 1 Gamma 1,EC50 were 7 nM and 6.8 nM. The activity of Alpha 1 beta 2 Gamma 1/Alpha 2 Beta 2 Gamma 1/Alpha 2 Beta 2 Gamma 3 subtype is very weak, EC50 greater than 4000 nM. |
| In vivo study | In rats, dogs, monkeys and humans, the binding rate of PF-06409577 to plasma protein was high. After intravenous injection, PF-06409577 had moderate plasma clearance (CLp) in rats, dogs and monkeys, which were 22.6/min/kg, 12.9/min/kg, 8.57/min/kg, stable distribution volume (0.846-3.15 L/kg). After oral administration of PF-06409577 (suspended in 0.5% methylcellose), it was rapidly absorbed in rats, dogs and monkeys, with oral bioavailability of 15%, 100% and 59%, respectively. In rats, PF-06409577 had a higher degree of aldose acidification than in other pre-clinical species and humans in the first pass of metabolism in the gut. |
PF 6409577 - Reference
| Reference Show more | 1. Cameron KO, et al. Discovery and Preclinical Characterization of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic Acid (PF-06409577), a Direct Activator of Adenosine Monophosphate-activated Protein Kinase (AMPK), for the Potential Treatment of Diabetic Nephropathy. J Med Chem. 2016 Sep 8;59(17):8068-81.2. Salatto CT, et al. Selective Activation of AMPK β1-Containing Isoforms Improves Kidney Function in a Rat Model of Diabetic Nephropathy. J Pharmacol Exp Ther. 2017 May;361(2):303-311. |
PF 6409577 - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.926 ml | 14.629 ml | 29.258 ml |
| 5 mM | 0.585 ml | 2.926 ml | 5.852 ml |
| 10 mM | 0.293 ml | 1.463 ml | 2.926 ml |
| 5 mM | 0.059 ml | 0.293 ml | 0.585 ml |
Last Update：2024-01-02 23:10:35
PF 6409577 - Reference Information
| Biological activity | PF-06409577 is an AMPK activator with oral activity. In TR-FRET experiments, the EC50 for AMPK α1β1γ1 is 7 nM. In patchBclamp experiments, 100 μM PF-06409577 had no appreciable inhibitory effect on hERG and no inhibitory activity on microsomal activity of the major human cytochrome P450 subtype (IC50 > 100 μM). |
| target | TargetValue AMPK α2β1γ1 () 6.8 nM(EC50) AMPK α1β1γ1 () 7 nM(EC50) |
| Target | Value |
| AMPK α2β1γ1 () | 6.8 nM(EC50) |
| AMPK α1β1γ1 () | 7 nM(EC50) |
| In vitro study | PF-06409577 can activate AMPK subtypes α1β1γ1 and α2β1γ1,EC50 are 7 nM and 6.8 nM respectively. Its activity against the α1β2γ1/α2β2γ1/α2β2γ3 subtype is very weak, with EC50 greater than 4000 nM. |
| In vivo studies | In rats, dogs, monkeys, and humans, PF-06409577 and plasma protein binding rate is high. After intravenous injection, PF-06409577 had moderate plasma clearance rates (CLp) of 22.6 mL/min/kg, 12.9 mL/min/kg and 8.57 mL/min/kg respectively in rats, dogs and monkeys, with stable distribution volume (0.846-3.15 L/kg). After oral PF-06409577 (suspended in 0.5% methylcellulose), it is rapidly absorbed in rats, dogs and monkeys, and its oral bioavailability is 15%, 100% and 59% respectively. In rats, the degree of aldose acidification response in the intestinal metabolism of the PF-06409577 was higher than in other preclinical species and humans. |
Last Update：2024-04-10 22:29:15
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Spot supply
Product Name: PF-06409577 Visit Supplier Webpage Request for quotationCAS: 1467057-23-3
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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