AX-024(AX-024) - 药物靶点：CD3ε x NCK_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

CD3ε x NCK

作用机制

CD3ε抑制剂(CD3e molecule inhibitors)、NCK抑制剂(Nck衔接蛋白-1抑制剂)

治疗领域

免疫系统疾病

在研适应症-

非在研适应症

自身免疫性疾病

原研机构

Artax Biopharma, Inc.

在研机构-

非在研机构

Artax Biopharma, Inc.

最高研发阶段无进展临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C21H22FNO2

InChIKeyVMMKGVRPILDZML-UHFFFAOYSA-N

CAS号1370544-73-2

关联

2

项与 AX-024 相关的临床试验

NCT02546635 / Completed临床1期

A Safety, Tolerability, and Pharmacokinetic Clinical Trial of AX-024.HCl to Evaluate A) Potential Food Effect and B) Multi-dosing in Healthy Male Subjects

Part A: Food effect (a single oral dose of 500 mg AX-024.HCl under fasted and fed states) Eight (8) healthy male volunteers will receive a single dose of 500 mg AX-024.HCl in the fasted state (10 h overnight fast), and will return 2 weeks later to receive the same dose of AX-024.HCl following a meal.
Part B: Multiple doses (a once daily dose of AX-024.HCl or Placebo for 10 days).
Part B is a double-blind, dose escalating, placebo controlled, randomised, multiple dose study to assess the tolerability, safety and pharmacokinetics in 24 healthy male subjects. Subjects will be allocated to one of 2 dosing cohorts. Each cohort will have 12 subjects with 9 subjects randomised to receive AX-024.HCl and 3 subjects randomised to receive placebo.
There will be a data review following each dose level. Dose administration in the subsequent cohorts will only proceed after satisfactory data review on the blinded safety data and plasma PK data in the previous cohort.

开始日期2015-08-01

申办/合作机构

Artax Biopharma, Inc.

[+1]

NCT02243683 / Completed临床1期

A Randomized, Placebo Controlled, Double Blind, Dose Escalating, Crossover, Safety and Pharmacokinetic Study of AX-024.HCl in Healthy Male Subjects

The purpose of this study is to determine the toxicity, tolerability and safety of single ascending doses of AX-024.HCl in healthy male subjects.

开始日期2014-09-01

申办/合作机构

Artax Biopharma, Inc.

[+3]

100 项与 AX-024 相关的临床结果

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100 项与 AX-024 相关的转化医学

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100 项与 AX-024 相关的专利（医药）

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6

项与 AX-024 相关的文献（医药）

2022-12-01·BMC Molecular and Cell Biology

Lack of Nck1 protein and Nck-CD3 interaction caused the increment of lipid content in Jurkat T cells

Article

作者: Rattanasri, Araya ; Ngoenkam, Jutaporn ; Wangteeraprasert, Apirath ; Nuiyen, Aussanee ; Pongcharoen, Sutatip ; Roytrakul, Sittiruk ; Wipa, Piyamaporn

AbstractBackgroundThe non-catalytic region of tyrosine kinase (Nck) is an adaptor protein, which is ubiquitously expressed in many types of cells. In T cells, the Nck1 isoform promotes T cell receptor signalling as well as actin polymerisation. However, the role of Nck1 in the lipid metabolism in T cells is unknown. In the present study, we investigated the effect of the Nck1 protein and Nck–CD3 interaction on lipid metabolism and on the physical and biological properties of Jurkat T cells, using a newly developed holotomographic microscope.ResultsHolotomographic microscopy showed that Nck1-knocked-out cells had membrane blebs and were irregular in shape compared to the rounded control cells. The cell size and volume of Nck1-deficient cells were comparable to those of the control cells. Nck1-knocked-out Jurkat T cells had a greater lipid content, lipid mass/cell mass ratio, and lipid metabolite levels than the control cells. Interestingly, treatment with a small molecule, AX-024, which inhibited Nck–CD3 interaction, also caused an increase in the lipid content in wild-type Jurkat T cells, as found in Nck1-deficient cells.ConclusionsKnockout of Nck1 protein and hindrance of the Nck–CD3 interaction cause the elevation of lipid content in Jurkat T cells.

2020-07-01·Journal of Biological Chemistry

Small molecule AX-024 targets T cell receptor signaling by disrupting CD3ε-Nck interaction

Letter

作者: Borroto, Aldo ; Alarcon, Balbino

2020-07-01·Journal of Biological Chemistry2区 · 生物学

Reply to Alarcon and Borroto: Small molecule AX-024 reduces T cell proliferation independently of CD3ε-Nck1 interaction at SH3.1

2区 · 生物学

Letter

作者: Muller, Magali ; Burger, Dominique ; Richter, Kirsten ; Huber, Sylwia ; Grossenbacher, Tabea ; Stoll, Theodor ; Casagrande, Fabio ; Rudolph, Markus G ; Rufer, Arne C ; Koldewey, Philipp ; Schlatter, Daniel ; Hug, Melanie N ; D'Osualdo, Andrea

100 项与 AX-024 相关的药物交易

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