Author: Manssour Fraga, Carlos Alberto ; Diniz, Luan Pereira ; Gomes, Flávia Carvalho Alcantara ; Sagrillo, Fernanda Savacini ; da Silva Antônio, Leticia Maria ; Morgado, Juliana ; Mota‐Araujo, Hannah Paola ; Figueiredo, Cláudia Pinto ; Bergamo Araujo, Ana Paula ; de Sena Murteira Pinheiro, Pedro ; Ferreira, Sérgio T. ; Cesar, Gabriele Vargas

Background and PurposeInhibitors of histone deacetylases (iHDACs) are promising drugs for neurodegenerative diseases. We have evaluated the therapeutic potential of the new iHDAC LASSBio‐1911 in Aβ oligomer (AβO) toxicity models and astrocytes, key players in neuroinflammation and Alzheimer's disease (AD).Experimental ApproachAstrocyte phenotype and synapse density were evaluated by flow cytometry, Western blotting, immunofluorescence and qPCR, in vitro and in mice. Cognitive function was evaluated by behavioural assays using a mouse model of intracerebroventricular infusion of AβO.Key ResultsLASSBio‐1911 modulates reactivity and synaptogenic potential of cultured astrocytes and improves synaptic markers in cultured neurons and in mice. It prevents AβO‐triggered astrocytic reactivity in mice and enhances the neuroprotective potential of astrocytes. LASSBio‐1911 improves behavioural performance and rescues synaptic and memory function in AβO‐infused mice.Conclusion and ImplicationsThese results contribute to unveiling the mechanisms underlying astrocyte role in AD and provide the rationale for using astrocytes as targets to new drugs for AD.

01 Aug 2024·Toxicology in Vitro

Selective inhibition of HDAC6 by N-acylhydrazone derivative reduces the proliferation and induces senescence in carcinoma hepatocellular cells

Article

Author: Ionta, Marisa ; Miyazawa, Marta ; Rodrigues, Daniel Alencar ; Pressete, Carolina Girotto ; Aissa, Alexandre Ferro ; Fraga, Carlos Alberto Manssour ; Ferreira-Silva, Guilherme Álvaro ; Hanemann, João Adolfo Costa ; Gamero, Angel Mauricio Castro ; Caixeta, Ester Siqueira

Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths globally. Systemic therapy is the only treatment option for HCC at an advanced stage, with limited therapeutic response. In this study, we evaluated the antitumor potential of four N-acylhydrazone (NAH) derivatives, namely LASSBio-1909, 1911, 1935, and 1936, on HCC cell lines. We have previously demonstrated that the aforementioned NAH derivatives selectively inhibit histone deacetylase 6 (HDAC6) in lung cancer cells, but their effects on HCC cells have not been explored. Thus, the present study aimed to evaluate the effects of NAH derivatives on the proliferative behavior of HCC cells. LASSBio-1911 was the most cytotoxic compound against HCC cells, however its effects were minimal on normal cells. Our results showed that LASSBio-1911 inhibited HDAC6 in HCC cells leading to cell cycle arrest and decreased cell proliferation. There was also an increase in the frequency of cells in mitosis onset, which was associated with disturbing mitotic spindle formation. These events were accompanied by elevated levels of CDKN1A mRNA, accumulation of CCNB1 protein, and sustained ERK1 phosphorylation. Furthermore, LASSBio-1911 induced DNA damage, resulting in senescence and/or apoptosis. Our findings indicate that selective inhibition of HDAC6 may provide an effective therapeutic strategy for the treatment of advanced HCC, including tumor subtypes with integrated viral genome. Further, in vivo studies are required to validate the antitumor effect of LASSBio-1911 on liver cancer.

100 Deals associated with LASSBio-1911

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Prostatic Cancer	Preclinical	BR	Federal University of Rio de Janeiro	21 Apr 2021

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

LASSBio-1911

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation