Delving into the Latest Updates on HARTIS Pharma SA with Synapse

概览

疾病领域	数量

血液及淋巴系统疾病	1

排名前五的药物类型	数量

小分子化药	1

排名前五的靶点	数量

BCAM	1

关联

2

项与 HARTIS Pharma SA 相关的药物

HRT-003

靶点

BCAM

作用机制

BCAM inhibitors

在研机构

HARTIS Pharma SA初创企业

原研机构

HARTIS Pharma SA初创企业

在研适应症

镰状细胞血症

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

HRT-001

靶点-

作用机制-

在研机构-

原研机构

HARTIS Pharma SA初创企业

在研适应症-

非在研适应症

镰状细胞血症

最高研发阶段无进展

首次获批国家/地区-

首次获批日期-

100 项与 HARTIS Pharma SA 相关的临床结果

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0 项与 HARTIS Pharma SA 相关的专利（医药）

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2

项与 HARTIS Pharma SA 相关的文献（医药）

2021-04-01·Circulation: Genomic and Precision Medicine2区 · 医学

Clinical Paradigm and Molecular Mechanisms in Precision Cardiovascular Medicine

2区 · 医学

Article

作者: Waters, David D. ; Wright, R. Scott ; Jukema, J. Wouter ; Tardif, Jean-Claude ; Brodeur, Mathieu R. ; Rhainds, David ; Sacks, Frank M. ; Pfeffer, Marc A. ; Laghrissi-Thode, Fouzia ; Heinonen, Therese ; Dubé, Marie-Pierre ; Packard, Chris J. ; Niesor, Eric J. ; Black, Donald M.

Following the neutral results of the dal-OUTCOMES trial, a genome-wide study identified the rs1967309 variant in the adenylate cyclase type 9 ( ADCY9 ) gene on chromosome 16 as being associated with the risk of future cardiovascular events only in subjects taking dalcetrapib, a CETP (cholesterol ester transfer protein) modulator. Homozygotes for the minor A allele (AA) were protected from recurrent cardiovascular events when treated with dalcetrapib, while homozygotes for the major G allele (GG) had increased risk. Here, we present the current state of knowledge regarding the impact of rs1967309 in ADCY9 on clinical observations and biomarkers in dalcetrapib trials and the effects of mouse ADCY9 gene inactivation on cardiovascular physiology. Finally, we present our current model of the interaction between dalcetrapib and ADCY9 gene variants in the arterial wall macrophage, based on the intracellular role of CETP in the transfer of complex lipids from endoplasmic reticulum membranes to lipid droplets. Briefly, the concept is that dalcetrapib would inhibit CETP-mediated transfer of cholesteryl esters, resulting in a progressive inhibition of cholesteryl ester synthesis and free cholesterol accumulation in the endoplasmic reticulum. Reduced ADCY9 activity, by paradoxically leading to higher cyclic AMP levels and in turn increased cellular cholesterol efflux, could impart cardiovascular protection in rs1967309 AA patients. The ongoing dal-GenE trial recruited 6145 patients with the protective AA genotype and will provide a definitive answer to whether dalcetrapib will be protective in this population.

Biomedicines

HDL as Bidirectional Lipid Vectors: Time for New Paradigms

Review

作者: Pérez-Méndez, Óscar ; Niesor, Eric ; Luna-Luna, María

The anti-atherogenic properties of high-density lipoproteins (HDL) have been explained mainly by reverse cholesterol transport (RCT) from peripheral tissues to the liver. The RCT seems to agree with most of the negative epidemiological correlations between HDL cholesterol levels and coronary artery disease. However, therapies designed to increase HDL cholesterol failed to reduce cardiovascular risk, despite their capacity to improve cholesterol efflux, the first stage of RCT. Therefore, the cardioprotective role of HDL may not be explained by RCT, and it is time for new paradigms about the physiological function of these lipoproteins. It should be considered that the main HDL apolipoprotein, apo AI, has been highly conserved throughout evolution. Consequently, these lipoproteins play an essential physiological role beyond their capacity to protect against atherosclerosis. We propose HDL as bidirectional lipid vectors carrying lipids from and to tissues according to their local context. Lipid influx mediated by HDL appears to be particularly important for tissue repair right on site where the damage occurs, including arteries during the first stages of atherosclerosis. In contrast, the HDL-lipid efflux is relevant for secretory cells where the fusion of intracellular vesicles drastically enlarges the cytoplasmic membrane with the potential consequence of impairment of cell function. In such circumstances, HDL could deliver some functional lipids and pick up not only cholesterol but an integral part of the membrane in excess, restoring the viability of the secretory cells. This hypothesis is congruent with the beneficial effects of HDL against atherosclerosis as well as with their capacity to induce insulin secretion and merits experimental exploration.

100 项与 HARTIS Pharma SA 相关的药物交易

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100 项与 HARTIS Pharma SA 相关的转化医学

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