srt2104 capsules  (Abbott Laboratories)

Journal: Scientific Reports

Article Title: Emerging roles of SIRT1 activator, SRT2104, in disease treatment

doi: 10.1038/s41598-024-55923-8

Figure Lengend Snippet: Interaction of SRT2104 with SIRT1. ( A ) Detailed binding profile of SRT2104 to SIRT1. ( B ) Illustrative representation of the molecular interaction between SRT2104 and SIRT1. Molecular docking simulations were conducted utilizing AutoDock software to model the interaction. A grid box measuring 126 Å in each dimension was established, with a grid point spacing of 0.375 Å. During the simulations, the ligands were allowed to flex, whereas the protein's amino acid residues were held fixed. The calculated binding energy served as a measure of affinity. Visualization of the interaction was enhanced using PyMol and Discover Studio, revealing that SRT2104 occupies the hydrophobic pocket of SIRT1. The amine group of SRT2104 forms hydrogen bonds with Gly269, Gln320, and Glu512 in the SIRT1 structure. Additionally, an oxygen atom of SRT2104 engages in a hydrogen bond with ARG282, contributing to the stability of the interaction. Hydrophobic contacts are further augmented by interactions between SRT2104 and SIRT1's Pro271, Arg282, Phe312, Lys314, and Phe321, including Pi-Pi stacking and alkyl interactions. Van der Waals forces involving Ile270, Ile279, Leu283, Ile316, Phe388, Ile510, and Thr511 also play a vital role in sustaining the interaction's stability.

Article Snippet: NCT00964340 , I , 24 , Healthy Elderly Subjects between 60 and 80 years of age , A Clinical Study to Assess the Safety, Tolerability and Pharmacokinetics of Oral SRT2104 Capsules Administered to Healthy Elderly Subjects for 28 Days , 2009-10-01 to 2010-04-27 , GlaxoSmithKline , United Kingdom.

Techniques: Binding Assay, Software

Journal: Scientific Reports

Article Title: Emerging roles of SIRT1 activator, SRT2104, in disease treatment

doi: 10.1038/s41598-024-55923-8

Figure Lengend Snippet: Clinical trials involving SRT2104.

Article Snippet: NCT00964340 , I , 24 , Healthy Elderly Subjects between 60 and 80 years of age , A Clinical Study to Assess the Safety, Tolerability and Pharmacokinetics of Oral SRT2104 Capsules Administered to Healthy Elderly Subjects for 28 Days , 2009-10-01 to 2010-04-27 , GlaxoSmithKline , United Kingdom.

Techniques: Clinical Proteomics, Activity Assay, Capsules, Drug discovery, Suspension, Formulation

Journal: Scientific Reports

Article Title: Emerging roles of SIRT1 activator, SRT2104, in disease treatment

doi: 10.1038/s41598-024-55923-8

Figure Lengend Snippet: Schematic representation of the molecular mechanisms mediated by SRT2104. SRT2104, through the activation of SIRT1, orchestrates a network of molecular pathways, including P53, STAT3, ZKSCANS, AMPK, GR, GSK3β/PTEN, NF-κB, β-catenin/Runx2, MAPK, Smad7, FOXO, and TORC1. These interactions collectively contribute to the amelioration of conditions such as lung injury, diabetic vascular complications, diabetic nephropathy, cognitive impairments associated with diabetes, musculoskeletal disorders, brain ischemia–reperfusion injury, Parkinson's disease (PD) neurodegeneration, and optic nerve damage. Key: "→" denotes activation or promotion, "⊥" indicates inhibition, "red arrow up" signifies upregulation, "green arrow down" signifies downregulation, and "Ac" refers to deacetylation.

Article Snippet: NCT00964340 , I , 24 , Healthy Elderly Subjects between 60 and 80 years of age , A Clinical Study to Assess the Safety, Tolerability and Pharmacokinetics of Oral SRT2104 Capsules Administered to Healthy Elderly Subjects for 28 Days , 2009-10-01 to 2010-04-27 , GlaxoSmithKline , United Kingdom.

Techniques: Activation Assay, Inhibition

Journal: Scientific Reports

Article Title: Emerging roles of SIRT1 activator, SRT2104, in disease treatment

doi: 10.1038/s41598-024-55923-8

Figure Lengend Snippet: Overview of the potential effects of SRT2104 on various organ systems. The diagram illustrates the compound's impact on key physiological processes across different tissues. “↓”denotes a decrease or impairment, while “↑” signifies an increase or enhancement. This figure summarizes the multifaceted pharmacological actions of SRT2104, suggesting its potential therapeutic applications.

Article Snippet: NCT00964340 , I , 24 , Healthy Elderly Subjects between 60 and 80 years of age , A Clinical Study to Assess the Safety, Tolerability and Pharmacokinetics of Oral SRT2104 Capsules Administered to Healthy Elderly Subjects for 28 Days , 2009-10-01 to 2010-04-27 , GlaxoSmithKline , United Kingdom.

Techniques:

Journal: Scientific Reports

Article Title: Emerging roles of SIRT1 activator, SRT2104, in disease treatment

doi: 10.1038/s41598-024-55923-8

Figure Lengend Snippet: Interaction of SRT2104 with SIRT1. ( A ) Detailed binding profile of SRT2104 to SIRT1. ( B ) Illustrative representation of the molecular interaction between SRT2104 and SIRT1. Molecular docking simulations were conducted utilizing AutoDock software to model the interaction. A grid box measuring 126 Å in each dimension was established, with a grid point spacing of 0.375 Å. During the simulations, the ligands were allowed to flex, whereas the protein's amino acid residues were held fixed. The calculated binding energy served as a measure of affinity. Visualization of the interaction was enhanced using PyMol and Discover Studio, revealing that SRT2104 occupies the hydrophobic pocket of SIRT1. The amine group of SRT2104 forms hydrogen bonds with Gly269, Gln320, and Glu512 in the SIRT1 structure. Additionally, an oxygen atom of SRT2104 engages in a hydrogen bond with ARG282, contributing to the stability of the interaction. Hydrophobic contacts are further augmented by interactions between SRT2104 and SIRT1's Pro271, Arg282, Phe312, Lys314, and Phe321, including Pi-Pi stacking and alkyl interactions. Van der Waals forces involving Ile270, Ile279, Leu283, Ile316, Phe388, Ile510, and Thr511 also play a vital role in sustaining the interaction's stability.

Article Snippet: NCT00938275 , I , 20 , Normal Healthy Volunteers between 18 and 55 years of age , A Clinical Study to Assess the Effect of Food and Gender on the Pharmacokinetics of SRT2104 Administered as an Oral Suspension or Capsule Formulation to Normal Healthy Volunteers , 2009-01-20 to 2009-03-27 , Sirtris, a GSK Company , United Kingdom.

Techniques: Binding Assay, Software

Journal: Scientific Reports

Article Title: Emerging roles of SIRT1 activator, SRT2104, in disease treatment

doi: 10.1038/s41598-024-55923-8

Figure Lengend Snippet: Clinical trials involving SRT2104.

Article Snippet: NCT00938275 , I , 20 , Normal Healthy Volunteers between 18 and 55 years of age , A Clinical Study to Assess the Effect of Food and Gender on the Pharmacokinetics of SRT2104 Administered as an Oral Suspension or Capsule Formulation to Normal Healthy Volunteers , 2009-01-20 to 2009-03-27 , Sirtris, a GSK Company , United Kingdom.

Techniques: Clinical Proteomics, Activity Assay, Capsules, Drug discovery, Suspension, Formulation

Journal: Scientific Reports

Article Title: Emerging roles of SIRT1 activator, SRT2104, in disease treatment

doi: 10.1038/s41598-024-55923-8

Figure Lengend Snippet: Schematic representation of the molecular mechanisms mediated by SRT2104. SRT2104, through the activation of SIRT1, orchestrates a network of molecular pathways, including P53, STAT3, ZKSCANS, AMPK, GR, GSK3β/PTEN, NF-κB, β-catenin/Runx2, MAPK, Smad7, FOXO, and TORC1. These interactions collectively contribute to the amelioration of conditions such as lung injury, diabetic vascular complications, diabetic nephropathy, cognitive impairments associated with diabetes, musculoskeletal disorders, brain ischemia–reperfusion injury, Parkinson's disease (PD) neurodegeneration, and optic nerve damage. Key: "→" denotes activation or promotion, "⊥" indicates inhibition, "red arrow up" signifies upregulation, "green arrow down" signifies downregulation, and "Ac" refers to deacetylation.

Article Snippet: NCT00938275 , I , 20 , Normal Healthy Volunteers between 18 and 55 years of age , A Clinical Study to Assess the Effect of Food and Gender on the Pharmacokinetics of SRT2104 Administered as an Oral Suspension or Capsule Formulation to Normal Healthy Volunteers , 2009-01-20 to 2009-03-27 , Sirtris, a GSK Company , United Kingdom.

Techniques: Activation Assay, Inhibition

Journal: Scientific Reports

Article Title: Emerging roles of SIRT1 activator, SRT2104, in disease treatment

doi: 10.1038/s41598-024-55923-8

Figure Lengend Snippet: Overview of the potential effects of SRT2104 on various organ systems. The diagram illustrates the compound's impact on key physiological processes across different tissues. “↓”denotes a decrease or impairment, while “↑” signifies an increase or enhancement. This figure summarizes the multifaceted pharmacological actions of SRT2104, suggesting its potential therapeutic applications.

Article Snippet: NCT00938275 , I , 20 , Normal Healthy Volunteers between 18 and 55 years of age , A Clinical Study to Assess the Effect of Food and Gender on the Pharmacokinetics of SRT2104 Administered as an Oral Suspension or Capsule Formulation to Normal Healthy Volunteers , 2009-01-20 to 2009-03-27 , Sirtris, a GSK Company , United Kingdom.

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: A phase II, randomized, placebo-controlled, double-blind, multi-dose study of SRT2104, a SIRT1 activator, in subjects with type 2 diabetes

doi: 10.1111/bcp.12327

Figure Lengend Snippet: Table 3

Article Snippet: Eight SRT2104 or matching placebo capsules were to be taken every morning approximately 15 min following consumption of a standardized meal (Ensure Plus, 237 ml bottle, Abbott Nutrition), as a food effect resulting in enhanced drug absorption had been previously demonstrated for this compound [ 13 ].

Techniques: