更新于：2024-11-01

MCT2 x MCT1

更新于：2024-11-01

基本信息

关联

项与 MCT2 x MCT1 相关的药物

AR-C155858

靶点

MCT1 x MCT2

作用机制

MCT1抑制剂 [+1]

在研机构-

原研机构

AstraZeneca PLC

在研适应症-

非在研适应症

乳腺癌

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 MCT2 x MCT1 相关的临床结果

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100 项与 MCT2 x MCT1 相关的转化医学

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0 项与 MCT2 x MCT1 相关的专利（医药）

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242

项与 MCT2 x MCT1 相关的文献（医药）

2024-10-01·Neuroscience Bulletin

Inhibition of YIPF2 Improves the Vulnerability of Oligodendrocytes to Human Islet Amyloid Polypeptide

Article

作者: Zhang, Yaxin ; Xing, Yuan ; Zhang, Nan ; Guo, Xin ; Ma, Xiaoying ; Zhang, Danshen ; Ma, Xiaowei ; Tian, Shujuan ; He, Xinyu ; Guo, Xiaosu ; Shen, Zhiyuan

Excessive secretion of human islet amyloid polypeptide (hIAPP) is an important pathological basis of diabetic encephalopathy (DE). In this study, we aimed to investigate the potential implications of hIAPP in DE pathogenesis. Brain magnetic resonance imaging and cognitive scales were applied to evaluate white matter damage and cognitive function. We found that the concentration of serum hIAPP was positively correlated with white matter damage but negatively correlated with cognitive scores in patients with type 2 diabetes mellitus. In vitro assays revealed that oligodendrocytes, compared with neurons, were more prone to acidosis under exogenous hIAPP stimulation. Moreover, western blotting and co-immunoprecipitation indicated that hIAPP interfered with the binding process of monocarboxylate transporter (MCT)1 to its accessory protein CD147 but had no effect on the binding of MCT2 to its accessory protein gp70. Proteomic differential analysis of proteins co-immunoprecipitated with CD147 in oligodendrocytes revealed Yeast Rab GTPase-Interacting protein 2 (YIPF2, which modulates the transfer of CD147 to the cell membrane) as a significant target. Furthermore, YIPF2 inhibition significantly improved hIAPP-induced acidosis in oligodendrocytes and alleviated cognitive dysfunction in DE model mice. These findings suggest that increased CD147 translocation by inhibition of YIPF2 optimizes MCT1 and CD147 binding, potentially ameliorating hIAPP-induced acidosis and the consequent DE-related demyelination.

2024-08-01·Veterinary Microbiology

Gene expression in heart, kidney, and liver identifies possible mechanisms underpinning fetal resistance and susceptibility to in utero PRRSV infection

Article

作者: Lunney, J K ; Walker, K E ; Mulligan, M K ; Harding, J C S ; Jones, A ; Van Goor, A ; Pasternak, J A

Porcine reproductive and respiratory syndrome (PRRS) is one of the costliest diseases to pork producers worldwide. We tested samples from the pregnant gilt model (PGM) to better understand the fetal response to in-utero PRRS virus (PRRSV) infection. Our goal was to identify critical tissues and genes associated with fetal resilience or susceptibility. Pregnant gilts (N=22) were infected with PRRSV on day 86 of gestation. At 21 days post maternal infection, the gilts and fetuses were euthanized, and fetal tissues collected. Fetuses were characterized for PRRS viral load in fetal serum and thymus, and preservation status (viable or meconium stained: VIA or MEC). Fetuses (N=10 per group) were compared: uninfected (UNIF; <1 log/µL PRRSV RNA), resilient (HV_VIA, >5 log virus/µL but viable), and susceptible (HV_MEC, >5 log virus/µL with MEC). Gene expression in fetal heart, kidney, and liver was investigated using NanoString transcriptomics. Gene categories investigated were hypothesized to be involved in fetal response to PRRSV infection: renin- angiotensin-aldosterone, inflammatory, transporter and metabolic systems. Following PRRSV infection, CCL5 increased expression in heart and kidney, and ACE2 decreased expression in kidney, each associated with fetal PRRS susceptibility. Liver revealed the most significant differential gene expression: CXCL10 decreased and IL10 increased indicative of immune suppression. Increased liver gene expression indicated potential associations with fetal PRRS susceptibility on several systems including blood pressure regulation (AGTR1), energy metabolism (SLC16A1 and SLC16A7), tissue specific responses (KL) and growth modulation (TGFB1). Overall, analyses of non-lymphoid tissues provided clues to mechanisms of fetal compromise following maternal PRRSV infection.

2024-07-02·Journal of Biomolecular Structure and Dynamics

Copper transporter protein (MctB) as a therapeutic target to elicit antimycobacterial activity against tuberculosis

Article

作者: Devi, Sreevidya S ; Dwivedi, Manish ; Jose, Sandra ; Raj, Ritu ; Gupta, Megha ; Kumar, Dinesh

Tuberculosis (TB) is a prehistoric infection and major etiologic agent of TB, Mycobacterium tuberculosis, which is considered to have advanced from an early progenitor species found in Eastern Africa. By the 1800s, there were approximately 800 to 1000 fatality case reports per 100,000 people in Europe and North America. This research suggests an In-silico study to identify potential inhibitory compounds for the target Mycobacterial copper transport protein (Mctb). ADME-based virtual screening, molecular docking, and molecular dynamics simulations were conducted to find promising compounds to modulate the function of the target protein. Four chemical compounds, namely Anti-MCT1, Anti-MCT2, Anti-MCT3 and Anti-MCT4 out of 1500 small molecules from the Diverse-lib of MTiOpenScreen were observed to completely satisfy Lipinski rule of five and Veber's rule. Further, significantly steady interactions with the MctB target protein were observed. Docking experiments have presented 9 compounds with less than -9.0 kcal/mol free binding energies and further MD simulation eventually gave 4 compounds having potential interactions and affinity with target protein and favorable binding energy ranging from -9.2 to -9.3 kcal/mol. We may propose these compounds as an effective candidate to reduce the growth of M. tuberculosis and may also assist present a novel therapeutic approach for Tuberculosis. In vivo and In vitro validation would be needed to proceed further in this direction.Communicated by Ramaswamy H. Sarma.