Delving into the Latest Updates on Pactimibe with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Acyl coenzyme A:cholesterol acyltransferase

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

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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18

Literatures (Medical) associated with Pactimibe

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 ; Burford, Michele A ; Chuang, Ann W ; 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.

01 Dec 2014·BMC GenomicsQ2 · BIOLOGY

Comparative genomics of Cylindrospermopsis raciborskii strains with differential toxicities

Q2 · BIOLOGY

ArticleOA

Author: Rati Sinha ; Timothy Walter Davis ; Julia Muenchhoff ; Ryanbi Pratama ; Michele Astrid Burford ; Brett A Neilan ; Aaron Jex ; Leanne A Pearson

BACKGROUNDCylindrospermopsis raciborskii is an invasive filamentous freshwater cyanobacterium, some strains of which produce toxins. Sporadic toxicity may be the result of gene deletion events, the horizontal transfer of toxin biosynthesis gene clusters, or other genomic variables, yet the evolutionary drivers for cyanotoxin production remain a mystery. Through examining the genomes of toxic and non-toxic strains of C. raciborskii, we hoped to gain a better understanding of the degree of similarity between these strains of common geographical origin, and what the primary differences between these strains might be. Additionally, we hoped to ascertain why some cyanobacteria possess the cylindrospermopsin biosynthesis (cyr) gene cluster and produce toxin, while others do not. It has been hypothesised that toxicity or lack thereof might confer a selective advantage to cyanobacteria under certain environmental conditions.RESULTSIn order to examine the fundamental differences between toxic and non-toxic C. raciborskii strains, we sequenced the genomes of two closely related isolates, CS-506 (CYN+) and CS-509 (CYN-) sourced from different lakes in tropical Queensland, Australia. These genomes were then compared to a third (reference) genome from C. raciborskii CS-505 (CYN+). Genome sizes were similar across all three strains and their G + C contents were almost identical. At least 2,767 genes were shared among all three strains, including the taxonomically important rpoc1, ssuRNA, lsuRNA, cpcA, cpcB, nifB and nifH, which exhibited 99.8-100% nucleotide identity. Strains CS-506 and CS-509 contained at least 176 and 101 strain-specific (or non-homologous) genes, respectively, most of which were associated with DNA repair and modification, nutrient uptake and transport, or adaptive measures such as osmoregulation. However, the only significant genetic difference observed between the two strains was the presence or absence of the cylindrospermopsin biosynthesis gene cluster. Interestingly, we also identified a cryptic secondary metabolite gene cluster in strain CS-509 (CYN-) and a second cryptic cluster common to CS-509 and the reference strain, CS-505 (CYN+).CONCLUSIONSOur results confirm that the most important factor contributing to toxicity in C. raciborskii is the presence or absence of the cyr gene cluster. We did not identify any other distally encoded genes or gene clusters that correlate with CYN production. The fact that the additional genomic differences between toxic and non-toxic strains were primarily associated with stress and adaptation genes suggests that CYN production may be linked to these physiological processes.

01 Nov 2010·AtherosclerosisQ2 · MEDICINE

A selective ACAT-1 inhibitor, K-604, stimulates collagen production in cultured smooth muscle cells and alters plaque phenotype in apolipoprotein E-knockout mice

Q2 · MEDICINE

Article

Author: Sohei Tanabe ; Haruki Shibata ; Yasunobu Yoshinaka ; Takuya Watanabe ; Akira Miyazaki ; Hideyuki Kobayashi ; Kimiyuki Shibuya ; Hiroki Kuriyama

Acyl-coenzyme A:cholesterol O-acyltransferase-1 (ACAT-1) plays an essential role in macrophage foam cell formation and progression of atherosclerosis. We developed a potent and selective ACAT-1 inhibitor, K-604, and tested its effects in apoE-knockout mice. Administration of K-604 to 8-week-old apoE-knockout mice for 12 weeks at a dose of 60 mg/kg/day significantly reduced macrophage-positive area and increased collagen-positive area in atherosclerotic plaques in the aorta without affecting plasma cholesterol levels or lesion areas, indicating direct plaque-modulating effects of K-604 on vascular walls independent of plasma cholesterol levels. Pactimibe, a nonselective inhibitor of ACAT-1 and ACAT-2, reduced plasma cholesterol levels but did not affect macrophage- or collagen-positive areas. The size of macrophages and cholesteryl ester contents in the aorta were reduced by K-604. Exposure of cultured human aortic smooth muscle cells to K-604 resulted in increased procollagen type 1 contents in the culture supernatant and increased procollagen type 1 mRNA levels. Procollagen production was unaffected by pactimibe even at a concentration that inhibited cholesterol esterification to the basal level. Thus, the plaque-modulating effects of K-604 can be explained by stimulation of procollagen production independent of ACAT inhibition in addition to potent inhibition of macrophage ACAT-1.

100 Deals associated with Pactimibe

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External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Heterozygous familial hypercholesterolemia	Phase 3	CA	Daiichi Sankyo Co., Ltd.	01 Feb 2004
Heterozygous familial hypercholesterolemia	Phase 3	NO	Daiichi Sankyo Co., Ltd.	01 Feb 2004
Heterozygous familial hypercholesterolemia	Phase 3	GB	Daiichi Sankyo Co., Ltd.	01 Feb 2004
Heterozygous familial hypercholesterolemia	Phase 3	ES	Daiichi Sankyo Co., Ltd.	01 Feb 2004
Heterozygous familial hypercholesterolemia	Phase 3	US	Daiichi Sankyo Co., Ltd.	01 Feb 2004
Heterozygous familial hypercholesterolemia	Phase 3	IL	Daiichi Sankyo Co., Ltd.	01 Feb 2004
Heterozygous familial hypercholesterolemia	Phase 3	ZA	Daiichi Sankyo Co., Ltd.	01 Feb 2004
Heterozygous familial hypercholesterolemia	Phase 3	SE	Daiichi Sankyo Co., Ltd.	01 Feb 2004
Heterozygous familial hypercholesterolemia	Phase 3	NL	Daiichi Sankyo Co., Ltd.	01 Feb 2004
Hyperlipidemias	Phase 3	-	Kyoto Pharmaceutical Industries Ltd.	-