Evidence map›Paper›PMID 26713267›Full record

ReviewActa pharmaceutica Sinica. B2015

Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors.

Marton Siklos, Manel BenAissa, Gregory R J Thatcher

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Acta pharmaceutica Sinica. B, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

111 citing papers in PubMed.

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  15. Neutrophil elastase activates macrophage calpain as a mechanism for phagocytic failure.American journal of physiology. Lung cellular and molecular physiology · 2025
    Article
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51 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Marton SiklosDepartment of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, IL 60612-7231, USA.
Manel BenAissaDepartment of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, IL 60612-7231, USA.
Gregory R J ThatcherDepartment of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, IL 60612-7231, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cysteine proteases continue to provide validated targets for treatment of human diseases. In neurodegenerative disorders, multiple cysteine proteases provide targets for enzyme inhibitors, notably caspases, calpains, and cathepsins. The reactive, active-site cysteine provides specificity for many inhibitor designs over other families of proteases, such as aspartate and serine; however, a) inhibitor strategies often use covalent enzyme modification, and b) obtaining selectivity within families of cysteine proteases and their isozymes is problematic. This review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders; the latter focus providing an interesting query for the contemporary assumptions that irreversible, covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.

Indexed as

AD, Alzheimer׳s diseaseAla, alanineALS, amyotrophic lateral sclerosisAlzheimer׳s diseaseAPP, amyloid precursor proteinAppLon, London familial amyloid precursor protein mutation, APP (V717I)APP/PS1, Aβ overexpressing mice APP (K670N/M671L) and PS1 (M146L) mutantsAppSwe, Swedish amyloid precursor protein mutation, APP (K670N/M671L)Arg, arginineAβ1-42, amyloid β, 42 amino acid proteinAβ, amyloid βBACE-1, β-amyloid cleaving enzymeBBB, blood–brain barrierCalpainCaMKII, Ca2+/calmodulin-dependent protein kinases IICANP, calcium-activated neutral proteaseCathepsinCdk5/p35, activator of cyclin-dependent kinase 5CNS, central nervous systemCREB, cyclic adenosine monophosphate response element binding proteinCysteine proteaseDTT, dithioerythritolEGFR, epidermal growth factor receptorEnzyme inhibitorsERK1/2, extracellular signal-regulated kinase 1/2Gln, glutamineGlu, glutamic acidGly, glutamineGSH, glutathioneHsp70.1, heat shock protein 70.1Ile, isoleucineisoAsp, isoaspartateKO, knockoutLeu, leucineLys, lysineMAP-2, microtubule-associated protein 2Met, methionineMMP-9, matrix metalloproteinase 9NeurodegenerationNFT, neurofibrilliary tanglesNle, norleucinePD, Parkinson׳s diseasepGlu, pyroglutamatePhe, phenylalaninePKC, protein kinase CPK, pharmacokineticPro, prolinePTP1B, protein-tyrosine phosphatase 1BpyroGluAβ, pyroglutamate-amyloid βSP, senile plaquesTBI, traumatic brain injuryThr, threonineTNF, tumor necrosis factorTyr, tyrosineVal, valineWRX, Trp-Arg containing epoxysuccinate cysteine protease inhibitorWT, wildtype

Identifiers

PMID26713267
PMCPMC4675809

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.