The primary objective of the study is to assess whether human subjects can be made tolerant to intravenously administered Crotoxin and achieve higher and more therapeutically effective doses levels without the previously reported adverse effects associated with bolus i.m. administration.

开始日期2024-08-01

申办/合作机构

Celtic Biotech Ltd.

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100 项与 Crotoxin 相关的临床结果

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100 项与 Crotoxin 相关的转化医学

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100 项与 Crotoxin 相关的专利（医药）

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293

项与 Crotoxin 相关的文献（医药）

2024-03-01·Biochimie

Structural studies with crotoxin B from Crotalus durissus collilineatus venom suggest a heterodimeric assembly formed by two new isoforms

Article

作者: Fontes, Marcos R M ; Borges, Rafael J ; Fernandes, Carlos A H ; Salvador, Guilherme H M ; Soares, Andreimar M

In accidents involving Crotalus snakes, the crotoxin complex (CTX) plays lethal action due to its neurotoxic activity. On the other hand, CTX have potential biotechnological application due to its anti-tumoral, anti-inflammatory, antimicrobial, analgesic and immunomodulatory properties. CTX is a heterodimer composed of Crotoxin A (CA or crotapotin), the acidic nontoxic and non-enzymatic component and; Crotoxin B (CB), a basic, toxic and catalytic PLA₂. Currently, there are two classes of CTX isoforms, whose differences in their biological activities have been attributed to features presented in CB isoforms. Here, we present the crystal structure of CB isolated from the Crotalus durissus collilineatus venom. It amino acid sequence was assigned using the SEQUENCE SLIDER software, which revealed that the crystal structure is a heterodimer composed of two new CB isoforms (colCB-A and colCB-B). Bioinformatic and biophysical analyses showed that the toxin forms a tetrameric assembly in solution similar to CB from Crotalus durissus terrificus venom, despite some differences observed at the dimeric interface. By the previously proposed classification, the colCB-B presents features of the class I isoforms while colCB-A cannot be classified into classes I and II based on its amino acid sequence. Due to similar features observed for other CB isoforms found in the NCBI database and the results obtained for colCB-A, we suggest that there are more than two classes of CTX and CB isoforms in crotalic venoms.

2023-07-01·International journal of biological macromolecules

Cytotoxic effect of crotoxin on cancer cells and its antitumoral effects correlated to tumor microenvironment: A review.

Review

作者: Lopes, Flávia Souza Ribeiro ; Picolo, Gisele ; Almeida, Tamires Cunha ; Boaventura de Oliveira, Ana Maria ; Sant'Anna, Morena Brazil ; Ribeiro Silva, Lorena de Morais

Cancer is the second leading cause of death worldwide, and despite the effort of standard treatments, the search for new tools against this disease is necessary. Importantly, it is known that the tumor microenvironment plays a crucial role in tumor initiation, progression, and response to therapies. Therefore, studies of potential drugs that act on these components are as critical as studies regarding antiproliferative substances. Through the years, studies of several natural products, including animal toxins, have been conducted to guide the development of medical compounds. In this review, we present the remarkable antitumor activities of crotoxin, a toxin from the rattlesnake Crotalus durissus terrificus, highlighting its effects on cancer cells and in the modulation of relevant elements in the tumor microenvironment as well as the clinical trials conducted with this compound. In summary, crotoxin acts through several mechanisms of action, such as activation of apoptosis, induction of cell cycle arrest, inhibition of metastasis, and decrease of tumor growth, in different tumor types. Crotoxin also modulates tumor-associated fibroblasts, endothelial cells, and immune cells, which contribute to its antitumoral effects. In addition, preliminary clinical studies confirm the promising results of crotoxin and support its potential future use as an anticancer drug.

2023-03-01·International Journal of Biological Macromolecules

Hemodynamic impairment induced by Crotoxin using in vivo and ex vivo approach in a rat model

Article

作者: Monteiro, Wuelton M ; Nogueira, Renato C ; Neto-Neves, Evandro M ; Cavalcante, Tavila T A ; Sousa, Lucas O ; Sampaio, Suely V ; Sartim, Marco A ; Cintra, Adélia C O

Crotalus durissus snakebite represent 10 % of snakebite cases in Brazil, which cardiovascular disorders are associated with severe cases. Considering crotoxin (CTX) as the major venom component, the present study aimed to evaluate the hemodynamic alterations induced by CTX using in vivo and ex vivo approaches in a rat model. In vivo cardiac function parameters were analyzed from anesthetized rats treated with CTX or saline only (Sham), along with serum creatine kinase MB (CK-MB) and lung myeloperoxidase. From the same animals, hearts were isolated and functional parameters evaluated in Langendorff method ex vivo. CTX binding to myoblast cell line in vitro were evaluated using confocal microscopy and flow cytometry. CTX was capable of reducing arterial and diastolic blood pressure, heart rate, along with left ventricle pressure development or decay during systole (LVdP/dt_max and LVdP/dt_min) in vivo, however no differences were found in the ex vivo approach, showing that intrinsic heart function was preserved. In vitro, CTX binding to myoblast cell line was mitigated by hexamethonium, a nicotinic acetylcholine receptor antagonist. The present study has shown that CTX induce hemodynamic failure in rats, which can help improve the clinical management of cardiovascular alterations during Crotalus durissus snakebite.

100 项与 Crotoxin 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
肿瘤	临床2期	-	Spotlight Innovation, Inc.	-
肿瘤	临床2期	-	Ventech Research Inc.	-
晚期癌症	临床1期	法国	Celtic Biotech Ltd.	2024-08-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


AACR2018	N/A	晚期癌症	6	Crotoxin	(餘顧鑰顧選鑰衊鹹觸鹹) = Patient was hospitalised for observation and the event was classified as a possible study drug-related SAE as well as related to the digestive syndrome and tubulopathy resulting from previous chemotherapy (nivolumab and platinum salts) 壓夢鹽獵鬱壓積製糧醖 (選餘遞餘積醖鏇艱襯網 )	-	2018-07-01