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MedKoo Cat#: 526836 | Name: PF-06409577
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Description:

WARNING: This product is for research use only, not for human or veterinary 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.

Chemical Structure

PF-06409577
PF-06409577
CAS#1467057-23-3

Theoretical Analysis

MedKoo Cat#: 526836

Name: PF-06409577

CAS#: 1467057-23-3

Chemical Formula: C19H16ClNO3

Exact Mass: 341.0819

Molecular Weight: 341.79

Elemental Analysis: C, 66.77; H, 4.72; Cl, 10.37; N, 4.10; O, 14.04

Price and Availability

Size Price Availability Quantity
5mg USD 280.00 2 Weeks
25mg USD 750.00 2 Weeks
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No Data
Synonym
PF-06409577; PF06409577; PF 06409577; PF-6409577; PF6409577; PF 6409577.
IUPAC/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)
SMILES Code
O=C(C1=CNC2=C1C=C(C3=CC=C(C4(O)CCC4)C=C3)C(Cl)=C2)O
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
PF-06409577 is a potent and selective allosteric activator of AMPK α1β1γ1 isoform with an EC50 of 7 nM.
In vitro activity:
PF-06409577 a novel, potent and direct AMP-activated protein kinase (AMPK) activator. In ARPE-19 cells and primary murine RPE cells, PF-06409577 significantly inhibited UVR-induced viability reduction, cell death and apoptosis. PF-06409577 activated AMPK signaling in RPE cells by increasing AMPKα1-acetyl-CoA carboxylase phosphorylation and AMPK activity. PF-06409577 enhanced nicotinamide adenine dinucleotide phosphate (NADPH) activity and expression levels of Nrf2-dependent genes in RPE cells. Reference: Biochem Biophys Res Commun. 2018 Jun 18;501(1):293-299. https://pubmed.ncbi.nlm.nih.gov/29733844/
In vivo activity:
The tumor growth curve results show that PF-06409577 oral administration significantly inhibited U2OS tumor growth in SCID mice (Figure 5A). When analyzing daily tumor growth, which was calculated by (tumor volume at Day-42 subtracting tumor volume at Day-0)/42, this study found that PF-06409577-treated U2OS tumors grew significantly slower than control tumors (Figure 5B). Thus, PF-06409577 oral administration potently inhibits U2OS xenograft tumor growth in SCID mice. Reference: Front Oncol. 2021 Jul 14;11:659181. https://pubmed.ncbi.nlm.nih.gov/34336655/
Solvent mg/mL mM comments
Solubility
DMSO 67.4 197.18
Ethanol 37.4 109.48
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 341.79 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Li XF, Liu XM, Huang DR, Cao HJ, Wang JY. PF-06409577 activates AMPK signaling to protect retinal pigment epithelium cells from UV radiation. Biochem Biophys Res Commun. 2018 Jun 18;501(1):293-299. doi: 10.1016/j.bbrc.2018.05.003. Epub 2018 May 8. PMID: 29733844. 2. Jiménez de Oya N, Blázquez AB, Casas J, Saiz JC, Martín-Acebes MA. Direct Activation of Adenosine Monophosphate-Activated Protein Kinase (AMPK) by PF-06409577 Inhibits Flavivirus Infection through Modification of Host Cell Lipid Metabolism. Antimicrob Agents Chemother. 2018 Jun 26;62(7):e00360-18. doi: 10.1128/AAC.00360-18. PMID: 29712653; PMCID: PMC6021616. 3. Su L, Yuan H, Zhang H, Wang R, Fu K, Yin L, Ren Y, Liu H, Fang Q, Wang J, Guo D. PF-06409577 inhibits renal cyst progression by concurrently inhibiting the mTOR pathway and CFTR channel activity. FEBS Open Bio. 2022 Oct;12(10):1761-1770. doi: 10.1002/2211-5463.13459. Epub 2022 Jul 4. PMID: 35748097; PMCID: PMC9527591. 4. Zhu YR, Zhang XY, Wu QP, Yu CJ, Liu YY, Zhang YQ. PF-06409577 Activates AMPK Signaling and Inhibits Osteosarcoma Cell Growth. Front Oncol. 2021 Jul 14;11:659181. doi: 10.3389/fonc.2021.659181. PMID: 34336655; PMCID: PMC8316637.
In vitro protocol:
1. Li XF, Liu XM, Huang DR, Cao HJ, Wang JY. PF-06409577 activates AMPK signaling to protect retinal pigment epithelium cells from UV radiation. Biochem Biophys Res Commun. 2018 Jun 18;501(1):293-299. doi: 10.1016/j.bbrc.2018.05.003. Epub 2018 May 8. PMID: 29733844. 2. Jiménez de Oya N, Blázquez AB, Casas J, Saiz JC, Martín-Acebes MA. Direct Activation of Adenosine Monophosphate-Activated Protein Kinase (AMPK) by PF-06409577 Inhibits Flavivirus Infection through Modification of Host Cell Lipid Metabolism. Antimicrob Agents Chemother. 2018 Jun 26;62(7):e00360-18. doi: 10.1128/AAC.00360-18. PMID: 29712653; PMCID: PMC6021616.
In vivo protocol:
1. Su L, Yuan H, Zhang H, Wang R, Fu K, Yin L, Ren Y, Liu H, Fang Q, Wang J, Guo D. PF-06409577 inhibits renal cyst progression by concurrently inhibiting the mTOR pathway and CFTR channel activity. FEBS Open Bio. 2022 Oct;12(10):1761-1770. doi: 10.1002/2211-5463.13459. Epub 2022 Jul 4. PMID: 35748097; PMCID: PMC9527591. 2. Zhu YR, Zhang XY, Wu QP, Yu CJ, Liu YY, Zhang YQ. PF-06409577 Activates AMPK Signaling and Inhibits Osteosarcoma Cell Growth. Front Oncol. 2021 Jul 14;11:659181. doi: 10.3389/fonc.2021.659181. PMID: 34336655; PMCID: PMC8316637.
1: Day EA, Townsend LK, Rehal S, Batchuluun B, Wang D, Morrow MR, Lu R, Lundenberg L, Lu JH, Desjardins EM, Smith TKT, Raphenya AR, McArthur AG, Fullerton MD, Steinberg GR. Macrophage AMPK β1 activation by PF-06409577 reduces the inflammatory response, cholesterol synthesis, and atherosclerosis in mice. iScience. 2023 Oct 20;26(11):108269. doi: 10.1016/j.isci.2023.108269. PMID: 38026185; PMCID: PMC10654588. 2: Achanta LB, Thomas DS, Housley GD, Rae CD. AMP-activated protein kinase activators have compound and concentration-specific effects on brain metabolism. J Neurochem. 2024 May;168(5):677-692. doi: 10.1111/jnc.15815. Epub 2023 Apr 6. PMID: 36977628. 3: Su L, Yuan H, Zhang H, Wang R, Fu K, Yin L, Ren Y, Liu H, Fang Q, Wang J, Guo D. PF-06409577 inhibits renal cyst progression by concurrently inhibiting the mTOR pathway and CFTR channel activity. FEBS Open Bio. 2022 Oct;12(10):1761-1770. doi: 10.1002/2211-5463.13459. Epub 2022 Jul 4. PMID: 35748097; PMCID: PMC9527591. 4: Nguyen-Tu MS, Harris J, Martinez-Sanchez A, Chabosseau P, Hu M, Georgiadou E, Pollard A, Otero P, Lopez-Noriega L, Leclerc I, Sakamoto K, Schmoll D, Smith DM, Carling D, Rutter GA. Opposing effects on regulated insulin secretion of acute vs chronic stimulation of AMP-activated protein kinase. Diabetologia. 2022 Jun;65(6):997-1011. doi: 10.1007/s00125-022-05673-x. Epub 2022 Mar 16. PMID: 35294578; PMCID: PMC9076735. 5: Zhu YR, Zhang XY, Wu QP, Yu CJ, Liu YY, Zhang YQ. PF-06409577 Activates AMPK Signaling and Inhibits Osteosarcoma Cell Growth. Front Oncol. 2021 Jul 14;11:659181. doi: 10.3389/fonc.2021.659181. PMID: 34336655; PMCID: PMC8316637. 6: Lapham K, Lin J, Novak J, Orozco C, Niosi M, Di L, Goosen TC, Ryu S, Riccardi K, Eng H, Cameron KO, Kalgutkar AS. 6-Chloro-5-[4-(1-Hydroxycyclobutyl)Phenyl]-1H-Indole-3-Carboxylic Acid is a Highly Selective Substrate for Glucuronidation by UGT1A1, Relative to β-Estradiol. Drug Metab Dispos. 2018 Dec;46(12):1836-1846. doi: 10.1124/dmd.118.083709. Epub 2018 Sep 7. PMID: 30194276. 7: Ryder TF, Calabrese MF, Walker GS, Cameron KO, Reyes AR, Borzilleri KA, Delmore J, Miller R, Kurumbail RG, Ward J, Kung DW, Brown JA, Edmonds DJ, Eng H, Wolford AC, Kalgutkar AS. Acyl Glucuronide Metabolites of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1 H-indole-3-carboxylic Acid (PF-06409577) and Related Indole-3-carboxylic Acid Derivatives are Direct Activators of Adenosine Monophosphate-Activated Protein Kinase (AMPK). J Med Chem. 2018 Aug 23;61(16):7273-7288. doi: 10.1021/acs.jmedchem.8b00807. Epub 2018 Aug 2. PMID: 30036059. 8: Foretz M, Viollet B. Activation of AMPK for a Break in Hepatic Lipid Accumulation and Circulating Cholesterol. EBioMedicine. 2018 May;31:15-16. doi: 10.1016/j.ebiom.2018.05.009. Epub 2018 May 10. PMID: 29754882; PMCID: PMC6014063. 9: Li XF, Liu XM, Huang DR, Cao HJ, Wang JY. PF-06409577 activates AMPK signaling to protect retinal pigment epithelium cells from UV radiation. Biochem Biophys Res Commun. 2018 Jun 18;501(1):293-299. doi: 10.1016/j.bbrc.2018.05.003. Epub 2018 May 8. PMID: 29733844. 10: Jiménez de Oya N, Blázquez AB, Casas J, Saiz JC, Martín-Acebes MA. Direct Activation of Adenosine Monophosphate-Activated Protein Kinase (AMPK) by PF-06409577 Inhibits Flavivirus Infection through Modification of Host Cell Lipid Metabolism. Antimicrob Agents Chemother. 2018 Jun 26;62(7):e00360-18. doi: 10.1128/AAC.00360-18. PMID: 29712653; PMCID: PMC6021616. 11: Esquejo RM, Salatto CT, Delmore J, Albuquerque B, Reyes A, Shi Y, Moccia R, Cokorinos E, Peloquin M, Monetti M, Barricklow J, Bollinger E, Smith BK, Day EA, Nguyen C, Geoghegan KF, Kreeger JM, Opsahl A, Ward J, Kalgutkar AS, Tess D, Butler L, Shirai N, Osborne TF, Steinberg GR, Birnbaum MJ, Cameron KO, Miller RA. Activation of Liver AMPK with PF-06409577 Corrects NAFLD and Lowers Cholesterol in Rodent and Primate Preclinical Models. EBioMedicine. 2018 May;31:122-132. doi: 10.1016/j.ebiom.2018.04.009. Epub 2018 Apr 8. PMID: 29673898; PMCID: PMC6014578. 12: Salatto CT, Miller RA, Cameron KO, Cokorinos E, Reyes A, Ward J, Calabrese MF, Kurumbail RG, Rajamohan F, Kalgutkar AS, Tess DA, Shavnya A, Genung NE, Edmonds DJ, Jatkar A, Maciejewski BS, Amaro M, Gandhok H, Monetti M, Cialdea K, Bollinger E, Kreeger JM, Coskran TM, Opsahl AC, Boucher GG, Birnbaum MJ, DaSilva-Jardine P, Rolph T. 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. doi: 10.1124/jpet.116.237925. Epub 2017 Mar 13. PMID: 28289077. 13: Cameron KO, Kung DW, Kalgutkar AS, Kurumbail RG, Miller R, Salatto CT, Ward J, Withka JM, Bhattacharya SK, Boehm M, Borzilleri KA, Brown JA, Calabrese M, Caspers NL, Cokorinos E, Conn EL, Dowling MS, Edmonds DJ, Eng H, Fernando DP, Frisbie R, Hepworth D, Landro J, Mao Y, Rajamohan F, Reyes AR, Rose CR, Ryder T, Shavnya A, Smith AC, Tu M, Wolford AC, Xiao J. 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. doi: 10.1021/acs.jmedchem.6b00866. Epub 2016 Aug 20. PMID: 27490827.