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Last update 08 May 2025

cruzain

Last update 08 May 2025

Basic Info

Synonyms-

Introduction-

Drugs associated with cruzain

K-777

Target

cruzain

Mechanism

cruzain inhibitors

Active Org.

Cornell University

Originator Org.

UCSF Medical Center [+1]

Active Indication

Chagas Disease

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

WRR-483

Target

cruzain

Mechanism

cruzain inhibitors

Active Org.-

Originator Org.

The Scripps Research Institute

Active Indication-

Inactive Indication

Chagas Disease

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with cruzain

100 Translational Medicine associated with cruzain

0 Patents (Medical) associated with cruzain

178

Literatures (Medical) associated with cruzain

25 Mar 2025·Current Medicinal Chemistry

Target Selectivity of Cysteine Protease Inhibitors: A Strategy to Address Neglected Tropical Diseases

Article

Author: de Jesus Marinho, Washley Phyama ; Nascimento, Igor José dos Santos ; de Oliveira Rios, Éric ; de Moura, Ricardo Olimpio

Abstract:Neglected tropical diseases (NTDs) are a group of infectious diseases that mainly affect the population living in poverty and without basic sanitation, causing severe damage to countries' economies. Among them, Leishmaniasis, Chagas disease, sleeping sickness, and related diseases such as Malaria stand out, which, despite being well known, have limited treatments based on old drugs and have high rates of parasite resistance. In addition, current drugs have an uncertain mechanism of action, and there is a need to identify new mechanisms to overcome problems related to side effects and resistance. In a sense, exploring cysteine proteases (CPs) may be a promising alternative that can lead to discovering innovative drugs that may be useful against these diseases. However, exploring CPs in drug discovery should be a cautious and rational process since parasitic CPs show a high degree of homology with human CPs, raising the need to identify increasingly specific patterns of target selectivity to identify safer drugs with fewer side effects. Finally, in this review, we present the main aspects related to the design of CP inhibitor drugs, highlighting structural features of ligands and targets that can be used in the design of new compounds against Leishmaniasis (LmCPB), Chagas disease (Cruzain), sleeping sickness (rhodesain) and malaria (falcipain). We hope our findings can guide researchers in searching for an innovative drug that can be used against these diseases that threaten the world population's health.

01 Feb 2025·European Journal of Medicinal Chemistry

Nanomolar activity of coumarin-3-thiosemicarbazones targeting Trypanosoma cruzi cruzain and the T. brucei cathepsin L-like protease

Article

Author: Cardoso, Sílvia Helena ; Padilha, Emanuelly Karla Araújo ; Ferreira, Luiz Alberto Santos ; Nunes, Jéssica Alves ; Santos-Júnior, Paulo Fernando da Silva ; Gomes, Midiane Correa ; Giardini, Miriam A ; Freitas, Johnnatan Duarte de ; Silva, Elany Barbosa da ; Zhan, Peng ; Kaur, Yashpreet ; Costa, Clara Andrezza Crisóstomo Bezerra ; Teixeira, Thaiz Rodrigues ; Mendonça-Junior, Francisco Jaime Bezerra ; Siqueira-Neto, Jair L ; Stanger, Emily J ; Silva-Júnior, Edeildo Ferreira da ; Araújo-Júnior, João Xavier de ; Caffrey, Conor R

Trypanosoma cruzi (T. cruzi) and Trypanosoma brucei (T. brucei) urgently demand innovative drug development due to their impact on public health worldwide. Their cysteine proteases, Cruzain (CRZ) and the T. brucei Cathepsin L-like protease (TbrCATL) are established drug targets for these parasites. In this study, our coumarin-3-thiosemicarbazones demonstrated nanomolar IC₅₀ values (22-698 nM) toward these proteases. Against T. cruzi amastigotes and T. brucei trypomastigotes, LASF-01 displayed a promising result. Herein, MCG-02, the most potent TbrCATL inhibitor, underwent comprehensive analyses, including cytotoxicity assessments and in vitro tests. Molecular dynamics (MD) simulations and a multiscale Quantum Mechanics/Quantum Mechanics (QM/QM) approach were used to generate insights into their binding modes. These suggested that MCG-02 could be a reversible, competitive covalent inhibitor. Further, confirmatory assays were experimentally performed changing different parameters to prove its efficacy. Additionally, the predicted pharmacokinetic profile showed that there is no violation of the Lipinski rule of five. Notably, coumarin-3-thiosemicarbazone hybrids emerged as promising candidates for designing highly active inhibitors against CRZ and TbrCATL. Overall, the integration of in silico and experimental approaches enhanced our understanding regarding the binding modes of MCG-02, which were experimentally corroborated, providing valuable insights for future drug development.

01 Dec 2024·Combinatorial Chemistry & High Throughput Screening

Molecular Dynamics of a N-Cyclohexyl-1,2,4-Oxadiazole Derivative as a Reversible Cruzain Inhibitor in Trypanosoma cruzi

Article

Author: Pinheiro, Cristian Vicson Gomes ; Marinho, Marcia Machado ; de Moura, Gabriel Acácio ; de Oliveira, Ronaldo Nascimento ; Nicolete, Roberto ; Rodrigues, João Pedro Viana ; Rocha, Yasmim Mendes

Background:Chagas disease kills around 10,000 people yearly, primarily in Latin America, where it is prevalent. Current treatment has limited chronic effectiveness, is unsafe, and has substantial side effects. As a result, the use of oxadiazole derivatives and similar heterocyclic compounds as bioisosteres are well known, and they are prospective candidates in the hunt for novel anti-Trypanosoma cruzi chemicals. Recent research has revealed that the cysteine protease cruzain from T. cruzi is a validated target for disease treatment.Objective:Thus, using a molecular dynamics simulation, the current study attempted to determine if a significant interaction occurred between the enzyme cruzain and its ligand.Results:Interactions with the catalytic site and other critical locations were observed. Also, the RMSD values suggested that the molecule under research had stable interactions with its target.Conclusion:Finally, the findings indicate that the investigated molecule 2b can interfere enzymatic activity of cruzain, indicating that it might be a promising antichagasic drug.

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cruzain

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