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- | PF-06409577 / Pfizer
Journal: AMPK activators have compound and concentration-specific effects on brain metabolism. (Pubmed Central) - May 18, 2024
Specific direct activation of ?1-containing AMPK isoforms with PF 06409577 resulted in increased Krebs cycle activity, restoring pyruvate metabolism while A769662 increased lactate and alanine production as well as labelling of citrate and glutamine. These results reveal a complex metabolic response to AMPK activators in brain beyond increased aerobic glycolysis and indicate that further research is warranted into their concentration and mechanism-dependent impact.
- | PF-06409577 / Pfizer
Journal: PF-06409577 inhibits renal cyst progression by concurrently inhibiting the mTOR pathway and CFTR channel activity. (Pubmed Central) - Oct 5, 2022
Our results demonstrated that PF-06409577 effectively down-regulated mammalian target of rapamycin (mTOR) pathway-mediated proliferation of cyst-lining epithelial cells and reduced cystic fibrosis transmembrane conductance regulator (CFTR)-regulated cystic fluid secretion. Overall, our data suggest that PF-06409577 holds therapeutic potential for ADPKD treatment.
- | PF-06409577 / Pfizer
Journal: Opposing effects on regulated insulin secretion of acute vs chronic stimulation of AMP-activated protein kinase. (Pubmed Central) - May 12, 2022
AMPK activation exerts complex, time-dependent effects on insulin secretion. These observations should inform the design and future clinical use of AMPK modulators.
- PF-06409577 / Pfizer
AMPK Reprograms Gene Expression and Promotes Adaptation/Survival in Response to Metabolic Stress through Binding to a Chromatin-Associated Transcription Complex in Acute Lymphoblastic Leukemia (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4975;
Additional experiments were conducted using the allosteric AMPK activators compound 991 and PF-06409577...In conclusion, our data show that in response to metabolic stress, AMPK binds directly to a multi-protein complex on chromatin to reprogram gene expression to promote cellular adaptation/survival in ALL. Further elucidation of AMPK’s interactions with members of the putative AMPK/chromatin-associated transcription complex may lead to unique opportunities for epigenetic-based therapeutic interventions and combination strategies to exploit synthetic lethality in relapse/refractory ALL and other hematological malignancies.
- | PF-06409577 / Pfizer
Journal: PF-06409577 Activates AMPK Signaling and Inhibits Osteosarcoma Cell Growth. (Pubmed Central) - Aug 3, 2021
AMPK activation, mTORC1 inhibition, autophagy induction, as well as RTK degradation and apoptosis activation were detected in PF-06409577-treated xenografts. In conclusion, activation of AMPK by PF-06409577 inhibits OS cell growth.
- | PF-06409577 / Pfizer
Journal: The AMP-Activated Protein Kinase Modulates Hypothermia-Induced J Wave. (Pubmed Central) - Mar 24, 2021
In conclusion, activation of AMPK by PF-06409577 inhibits OS cell growth. AMPK inhibition reduces low-temperature-induced J waves and possible ventricular arrhythmogenesis by modulating I and I channels.
- Venclexta (venetoclax) / Roche, AbbVie, PF-06409577 / Pfizer
PKR-like Endoplasmic Reticulum Kinase Mediates Apoptosis Induced By Pharmacological AMP-Activated Protein Kinase Activation in Acute Myeloid Leukemia (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_3721;
Cell Rep . 2015;11(9):1446–1457.
- | PF-06409577 / Pfizer
Journal: Acyl Glucuronide Metabolites of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic Acid (PF-06409577) and Related Indole-3-carboxylic Acid Derivatives are Direct Activators of Adenosine Monophosphate-activated Protein Kinase (AMPK). (Pubmed Central) - Oct 16, 2019
Inhibition of de novo lipogenesis with representative parent carboxylic acids and their respective acyl glucuronide conjugates in human hepatocytes demonstrated their propensity to activate cellular AMPK. Co-crystallization of the AMPK α1β1γ1 isoform with 1-3 and M1-M3 provided molecular insights into the structural basis for AMPK activation by the glucuronide conjugates.
- | PF-06409577 / Pfizer
Journal: Direct Activation of Adenosine Monophosphate-Activated Protein Kinase (AMPK) by PF-06409577 Inhibits Flavivirus Infection through Modification of Host-Cell Lipid Metabolism. (Pubmed Central) - Sep 18, 2019
This antiviral effect was associated to an impairment of viral replication due to the modulation of host cell lipid metabolism exerted by the compound. These results support that the pharmacological activation of AMPK, which currently constitutes an important pharmacological target for human diseases, could also provide a feasible approach for broad-spectrum host-directed antiviral discovery.
- | PF-06409577 / Pfizer
Journal: 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic Acid (PF-06409577) is a Highly Selective Substrate for Glucuronidation by Uridine Diphosphoglucuronosyl Transferase (UGT) 1A1, Relative to b-Estradiol. (Pubmed Central) - May 29, 2019
RAF values from PF-06409577 and ES were generally comparable with the exception of intestinal microsomes where ES over-estimated the RAF of UGT1A1 due to glucuronidation by intestinal UGT1A8 and UGT1A10. Our results suggest a potential utility of PF-06409477 as a selective probe UGT1A1 substrate for UGT reaction phenotyping and inhibition studies in preclinical discovery/development.
- PF-06409577 / Pfizer
Enrollment change, Trial termination: A Single Oral Dose Study Of PF-06409577 In Healthy Adult Subjects (clinicaltrials.gov) - Jul 20, 2015
P1, N=39, Terminated, Sponsor: Pfizer
N=72 --> 39 | Recruiting --> Terminated; The trial was terminated prematurely on June 19, 2015 for business reasons. There were no safety concerns in the study which led to the decision.
- ||| PF-06409577 / Pfizer
Enrollment open: A Single Oral Dose Study Of PF-06409577 In Healthy Adult Subjects (clinicaltrials.gov) - May 28, 2015
P1, N=72, Recruiting, Sponsor: Pfizer
There were no safety concerns in the study which led to the decision. Suspended --> Recruiting
- | PF-06409577 / Pfizer
Trial suspension, Trial primary completion date: A Single Oral Dose Study Of PF-06409577 In Healthy Adult Subjects (clinicaltrials.gov) - Mar 14, 2015
P1, N=64, Suspended, Sponsor: Pfizer
Suspended --> Recruiting Recruiting --> Suspended | Trial primary completion date: Mar 2015 --> Sep 2015
- ||| PF-06409577 / Pfizer
Enrollment open: A Single Oral Dose Study Of PF-06409577 In Healthy Adult Subjects (clinicaltrials.gov) - Jan 9, 2015
P1, N=64, Recruiting, Sponsor: Pfizer
Recruiting --> Suspended | Trial primary completion date: Mar 2015 --> Sep 2015 Not yet recruiting --> Recruiting
- ||| PF-06409577 / Pfizer
New P1 trial: A Single Oral Dose Study Of PF-06409577 In Healthy Adult Subjects (clinicaltrials.gov) - Nov 10, 2014
P1, N=56, Not yet recruiting, Sponsor: Pfizer