Delving into the Latest Updates on Pactimibe with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Acyl coenzyme A:cholesterol acyltransferase

Action

inhibitors

Mechanism

Acyl coenzyme A:cholesterol acyltransferase inhibitors

Therapeutic Areas

Cardiovascular DiseasesEndocrinology and Metabolic DiseaseNervous System Diseases+ [1]

Active Indication-

Inactive Indication

AtherosclerosisCarotid Artery DiseasesCoronary Artery Disease+ [3]

Originator Organization

Kyoto Pharmaceutical Industries Ltd.

Active Organization-

Inactive Organization

Daiichi Sankyo Co., Ltd.

Daiichi Sankyo, Inc.

Kyoto Pharmaceutical Industries Ltd.

+ [1]

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC25H40N2O3

InChIKeyTXIIZHHIOHVWJD-UHFFFAOYSA-N

CAS Registry189198-30-9

A Randomized, Double-blind, Stratified, Placebo-controlled, Parallel-group Study of the Efficacy and Safety of the ACAT Inhibitor CS-505 for Reducing the Progression of Atherosclerosis in Subjects With Heterozygous Familial Hypercholesterolemia and Carotid Atherosclerosis Using Carotid Ultrasound (CUS)

The effects of pactimibe versus placebo on the progression of atherosclerosis in the carotid arteries will be assessed using standard ultrasound techniques.

Start Date01 Feb 2004

Sponsor / Collaborator

Daiichi Sankyo, Inc.

NCT00185042

/ CompletedPhase 2

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Efficacy and Safety of the ACAT Inhibitor CS-505 for Reducing the Progression of Atherosclerosis in Subjects With Coronary Artery Disease Using Intravascular Ultrasound (IVUS)

The purpose of this study is to learn if CS-505 is safe and effective for slowing down or possibly reversing the buildup of tissue, cells and fatty deposits (plaque) in the blood vessels of the heart (coronary artery atherosclerosis).

Start Date01 Nov 2002

Sponsor / Collaborator

Daiichi Sankyo, Inc.

NCT00185146

/ CompletedPhase 2

Effect of Pactimibe on the Progression of Atherosclerosis as Measured by 2-D and 3-D Carotid Ultrasound

The effect of pactimibe on the reduction of atherosclerosis in the carotid artery will be assessed using carotid ultrasound

Start Date01 Sep 2002

Sponsor / Collaborator

Sankyo Pharma GmbH

100 Clinical Results associated with Pactimibe

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100 Translational Medicine associated with Pactimibe

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100 Patents (Medical) associated with Pactimibe

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26

Literatures (Medical) associated with Pactimibe

01 Nov 2024·Journal of Computational Biophysics and Chemistry

Molecular Docking, Quantum Mechanics and Molecular Dynamics Simulation of Anti-CAD Drugs Against High-Risk Xanthine Dehydrogenase Variants Associated with Oxidative Stress Pathways

Author: Ahmed, Shiek S. S. J. ; Ahmad, Sheikh F. ; Emran, Talha Bin ; Janakiraman, V. ; Attia, Sabry M. ; Sudhan, M.

Xanthine dehydrogenase (XDH) contributes significantly to generating reactive oxygen species in coronary artery disease (CAD). XDH has been proposed as a therapeutic target, but its genetic variants could affect protein structure and drug response. We aimed to assess protein structure modification occur due to genetic variants and to screen 215 CAD drugs for their utility in personalized CAD treatment against the XDH variants. A series of computational methods were implemented to identify pathogenic variants that cause XDH structure instability localized at the con served regions contributing to functional significance. Then, the XDH structures with the pathogenic variants were modeled using two different approaches to select the best models for docking with the CAD drugs. Finally, the stability of the docked complexes and their ability to transfer electrons were evaluated using molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculation. Among 751 variants examined; R149C and Q919R showed high pathogenicity, localized in conserved regions could alter protein structure and function. Further, docking of CAD drugs against XDH (native, R149C and Q919R) showed vericiguat with higher affinity, ranging from −7.95 kcal/mol to −10.41 kcal/mol, than the well-known XDH inhibitor (febuxostat, −5.73 kcal/mol to −8.35 kcal/mol). This indicates that vericiguat will be effective in CAD treatment, regardless of the XDH variants. Additionally, MD simulation and QM/MM confirmed vericiguat stability and electron transfer ability to form hydrogen bonds with the XDH protein. In conclusion, vericiguat will be beneficial for the personalized treatment of CAD by inhibiting XDH variants. Additional clinical studies are necessary to confirm our findings.

01 Feb 2019·Harmful AlgaeQ2 · BIOLOGY

Differential expression of phosphorus acquisition genes in response to phosphorus stress in two Raphidiopsis raciborskii strains

Q2 · BIOLOGY

Article

Author: Willis, Anusuya ; Chuang, Ann W ; Burford, Michele A ; Dyhrman, Sonya

The cyanobacterium Raphidiopsis raciborskii is a nuisance in freshwater ecosystems. Strains vary in their physiological responses to environmental drivers, thus a greater understanding of the magnitude of strain variation is required to characterize the species. In this study, two strains of R. raciborskii isolated from a tropical Australian water reservoir were grown with and without phosphorus (P) to determine any relative response to P stress. The strains had the same growth rates and under P free conditions, cells grew at the same rate as P replete conditions until day 9 when cell growth ceased. There was no difference in the alkaline phosphatase activity per cell for the P replete and P free conditions, but the level of activity per cell was greater in CS-505 than CS-506. P acquisition genes were identified from the sequenced genomes; both strains contained the same genes, but with differences in copy number of phoA (7 and 6), phnK (3 and 1) and phnH (2 and 1) between CS-505 and CS-506 (respectively). The expression of P acquisition genes under P stress was measured throughout the experiment and shown to vary in magnitude and timing across strains, and in P replete versus P free cultures. In strain CS-505, upregulation of the pstS1 and phoA genes occurred late in the growth phase and into senescence. These genes are involved in phosphate uptake and use of various forms of organic P. For strain CS-506, there was upregulation of the phosphate uptake gene, pit, and organic P utilization genes, phoA, phoU, phnD and phnK, commencing late in the growth phase. Our study shows that despite the fact that these two strains were isolated from the same waterbody, they differed markedly in their gene expression response to P free conditions. This capacity of R. raciborskii to vary in strain responses to P conditions gives the organism flexibility in responding to environmental change, particularly P stress conditions.

14 Jul 2018·European Heart JournalQ1 · MEDICINE

Visit-to-visit cholesterol variability correlates with coronary atheroma progression and clinical outcomes

Q1 · MEDICINE

Article

Author: Nissen, Steven E ; St. John, Julie ; Clark, Donald ; Tuzcu, E Murat ; Nicholls, Stephen J ; Kapadia, Samir R ; Puri, Rishi ; Elshazly, Mohamed B

AimsUtilizing serial intravascular ultrasonography (IVUS), we aimed to exam the association of intra-individual lipid variability, coronary atheroma progression, and clinical outcomes.Methods and resultsWe performed a post hoc patient-level analysis of nine clinical trials involving 4976 patients with coronary artery disease who underwent serial coronary IVUS in the setting of a range of medical therapies. We assessed the associations between progression in percent atheroma volume (ΔPAV), clinical outcomes, and visit-to-visit lipid variability including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC)/HDL-C, and apolipoprotein B (ApoB). Variability of lipid parameters was measured using intra-individual standard deviation over 3, 6, 12, 18, and 24 months. Atherogenic lipoprotein variability significantly associated with ΔPAV [odds ratio (95% confidence interval; P-value), LDL-C: 1.09 (1.02, 1.17, P = 0.01); non-HDL-C: 1.10 (1.02, 1.18, P = 0.01); TC/HDL-C: 1.14 (1.06, 1.24, P = 0.001); ApoB: 1.13 (1.03, 1.24, P = 0.01)]. Survival curves revealed significant stepwise relationships between cumulative major adverse cardiovascular events and increasing quartiles of atherogenic lipoprotein variability at 24-months follow-up (log-rank P < 0.01 for all lipoproteins except HDL-C). Stronger associations were noted between achieved lipoprotein levels and ΔPAV [LDL-C: 1.27 (1.17, 1.39; P < 0.001); non-HDL-C: 1.32 (1.21, 1.45; P < 0.001); TC/HDL-C: 1.31 (1.19, 1.45; P < 0.001); ApoB: 1.20 (1.07, 1.35; P = 0.003)].ConclusionGreater visit-to-visit variability in atherogenic lipoprotein levels significantly associates with coronary atheroma progression and clinical outcomes, although the association between achieved atherogenic lipoproteins and atheroma progression appears stronger. These data highlight the importance of achieving low and consistent atherogenic lipoprotein levels to promote plaque regression and improve clinical outcomes.

100 Deals associated with Pactimibe

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hyperlipoproteinemia Type II	Phase 3	Sweden	Daiichi Sankyo, Inc.	01 Feb 2004
Hyperlipoproteinemia Type II	Phase 3	Netherlands	Daiichi Sankyo, Inc.	01 Feb 2004
Hyperlipoproteinemia Type II	Phase 3	South Africa	Daiichi Sankyo, Inc.	01 Feb 2004
Hyperlipoproteinemia Type II	Phase 3	Israel	Daiichi Sankyo, Inc.	01 Feb 2004
Hyperlipoproteinemia Type II	Phase 3	United States	Daiichi Sankyo, Inc.	01 Feb 2004
Hyperlipoproteinemia Type II	Phase 3	Norway	Daiichi Sankyo, Inc.	01 Feb 2004
Hyperlipoproteinemia Type II	Phase 3	Spain	Daiichi Sankyo, Inc.	01 Feb 2004
Hyperlipoproteinemia Type II	Phase 3	United Kingdom	Daiichi Sankyo, Inc.	01 Feb 2004
Hyperlipoproteinemia Type II	Phase 3	Canada	Daiichi Sankyo, Inc.	01 Feb 2004
Hyperlipidemias	Phase 3	-	Kyoto Pharmaceutical Industries Ltd.	-