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更新于：2025-05-07

CAPN1

更新于：2025-05-07

基本信息

别名

Calcium-activated neutral proteinase 1、calpain 1、calpain 1, (mu/I) large subunit

+ [11]

简介

Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction (PubMed:19617626, PubMed:21531719, PubMed:2400579). Proteolytically cleaves CTBP1 at 'Asn-375', 'Gly-387' and 'His-409' (PubMed:23707407). Cleaves and activates caspase-7 (CASP7) (PubMed:19617626).

关联

项与 CAPN1 相关的药物

MASH(Repair)

靶点

CAPN1

作用机制

CAPN1抑制剂

在研机构

Repair Biotechnologies, Inc.

原研机构

Repair Biotechnologies, Inc.

在研适应症

非酒精性脂肪性肝炎

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1800-01-20

CAT-1001

靶点

CAPN1 x CAPN2

作用机制

CAPN1抑制剂 [+1]

在研机构

Calpain Therapeutics Pty Ltd

原研机构

Calpain Therapeutics Pty Ltd

在研适应症

青光眼

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1800-01-20

BLD-2736

靶点

CAPN1 x CAPN2 x CAPN9 x CTSK

作用机制

CAPN1抑制剂 [+3]

在研机构

Macquarie University [+1]

原研机构

Blade Therapeutics, Inc.

在研适应症

马查多-约瑟夫病

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1800-01-20

项与 CAPN1 相关的临床试验

NCT02573740

/ Terminated临床1期

A Study to Evaluate the Safety, Tolerability and the Effects on Cerebrospinal Fluid Spectrin Breakdown Product-145 Levels of Multiple Doses of ABT-957 in Subjects With Mild Alzheimer's Disease and Mild Cognitive Impairment Due to Alzheimer's Disease

This is a Phase 1, multicenter, randomized, double-blind, placebo-controlled, multiple dose study of ABT-957 in participants with mild Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) due to AD.

开始日期2015-12-01

申办/合作机构

AbbVie, Inc.

NCT02220738

/ Terminated临床1期

A Multiple-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ABT-957 in Subjects With Mild-to-Moderate Alzheimer's Disease on Stable Doses of Acetylcholinesterase Inhibitors

This study is designed to evaluate the safety, tolerability and pharmacokinetics of multiple doses of ABT-957 in subjects with mild to moderate Alzheimer's disease.

开始日期2014-09-01

申办/合作机构

AbbVie, Inc.

EUCTR2005-003783-27-AT

/ Not yet recruitingN/A

TOLERABILITY OF ENECADIN (INN) IN ACUTE ISCHEMIC STROKE TRIAL - TEST- PHASE IIA : A multicentre, double-blind, randomised, placebo-controlled, dose-escalating parallel- group study to investigate the tolerability of enecadin (INN) in acute ischemic stroke - TEST

开始日期2007-04-20

申办/合作机构

Paion Deutschland GmbH

100 项与 CAPN1 相关的临床结果

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100 项与 CAPN1 相关的转化医学

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0 项与 CAPN1 相关的专利（医药）

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7,474

项与 CAPN1 相关的文献（医药）

2025-12-31·Renal Failure

Piezo1 aggravates ischemia/reperfusion-induced acute kidney injury by Ca ²⁺ -dependent calpain/HIF-1α/Notch signaling

Article

作者: Liu, Silin ; Tan, Qiaorui ; He, Bin ; Xu, Honglin ; Chen, Xiaoting ; Li, Jing ; Chen, Xin ; Jiang, Jintao ; Pan, Xianmei ; Wan, Rentao ; Yao, Youfen ; Luo, Shangfei

Macrophages play a vital role in the inflammation and repair processes of ischemia/reperfusion-induced acute kidney injury (IR-AKI). The mechanosensitive ion channel Piezo1 is significant in these inflammatory processes. However, the exact role of macrophage Piezo1 in IR-AKI is unknown. The main purpose of this study was to determine the role of macrophage Piezo1 in the injury and repair process in IR-AKI. Genetically modified mice with targeted knockout of Piezo1 in myeloid cells were established, and acute kidney injury was induced by bilateral renal vascular clamping surgery. Additionally, hypoxia treatment was performed on bone marrow-derived macrophages in vitro. Our data indicate that Piezo1 is upregulated in renal macrophages in mice with IR-AKI. Myeloid Piezo1 knockout provided protective effects in mice with IR-AKI. Mechanistically, the regulatory effects of Piezo1 on macrophages are at least partially linked to calpain signaling. Piezo1 activates Ca²⁺-dependent calpain signaling, which critically upregulates HIF-1α signaling. This key pathway subsequently influences the Notch and CCL2/CCR2 pathways, driving the polarization of M1 macrophages. In conclusion, our findings elucidate the biological functions of Piezo1 in renal macrophages, underscoring its role as a crucial mediator of acute kidney injury. Consequently, the genetic or pharmacological inhibition of Piezo1 presents a promising strategy for treating IR-AKI.

2025-12-31·OncoImmunology

Calpain 2 regulates IL-1α secretion and inhibits tumor development via modulating calpain 1 expression in the tumor microenvironment

Article

作者: Teo, Huey Yee ; Chiu, Jing Wen ; Liu, Haiyan ; Lu, Jinhua ; Binte Hanafi, Zuhairah ; Mei, Yu ; Zhu, Ying ; Yong Lionel, Chew Chin

Tumor-promoting inflammation significantly impacts cancer progression, and targeting inflammatory cytokines has emerged as a promising therapeutic approach in clinical trials. Interleukin (IL)-1α, a member of the IL-1 cytokine family, plays a crucial role in both inflammation and carcinogenesis. How IL-1α is secreted in the tumor microenvironment has been poorly understood, and we previously showed that calpain 1 cleaves pro-IL-1α for mature IL-1α secretion, which exacerbates hepatocellular carcinoma by recruiting myeloid-derived suppressor cells. In this study, we report that calpain 2 also modulates IL-1α secretion. Notably, a deficiency in calpain 2 resulted in enhanced hepatocellular carcinoma development within an IL-1α-enriched tumor microenvironment. Further investigations revealed that calpain 2 deficiency increased calpain 1 expression, implying a compensatory mechanism between the two calpains. Mechanistically, calpain 2 deficiency led to increased expression of FoxO3, which is a forkhead transcription factor that promotes calpain 1 expression. Collectively, these results suggest that calpain 2 modulates calpain 1 expression, and therefore IL-1α secretion through the induction of FoxO3, offering novel potential therapeutic targets for cancer treatment.

2025-07-01·Neurobiology of Aging

Calpain and caspase regulate Aβ peptide production via cleavage of KINDLIN2 encoded by the AD-associated gene FERMT2

Article

作者: Buiche, Valérie ; Demiautte, Florie ; Lambert, Erwan ; Eysert, Fanny ; Coulon, Audrey ; Kilinc, Devrim ; Siedlecki-Wullich, Dolores ; Amouyel, Philippe ; Walle, Pauline ; Najdek, Chloé ; Lambert, Jean-Charles ; Gelle, Carla ; Flaig, Amandine ; Dumont, Julie ; Ayral, Anne-Marie ; Chapuis, Julien

The adapter protein KINDLIN2, encoded by the Alzheimer's disease (AD) genetic risk factor FERMT2, was identified as a modulator of APP processing. KINDLIN2 directly interacts with APP to modulate its metabolism, and KINDLIN2 underexpression impairs long-term potentiation in an APP-dependent manner. Altogether, these data suggest that loss of KINDLIN2 could have a detrimental effect on synaptic function and promote AD pathophysiological process. In this study, we identified KINDLIN2 as a novel substrate of caspases and calpain I, two well-characterized cysteine proteases involved in the regulation of synaptic plasticity. These cleavages resulted in the dissociation of the F0 and F1 domains of KINDLIN2 that are necessary for it to function as an adapter protein. Furthermore, we demonstrate that these cleavages lead to a decrease in KINDLIN2's ability to control APP processing. Overall, these KINDLIN2 cleavages appear as potential new mechanisms in the regulation of KINDLIN2 functions at the synapse and could be of interest for the pathophysiology of AD.