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Repurposing Vorinostat for the Treatment of Disorders Affecting Brain.
Athira, K V; Sadanandan, Prashant; Chakravarty, Sumana.
Afiliação
  • Athira KV; Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Amrita Institute of Medical Sciences Health Sciences Campus, Kochi, 682 041, Kerala, India. athirakv@aims.amrita.edu.
  • Sadanandan P; Department of Pharmaceutical Chemistry & Analysis, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Amrita Institute of Medical Sciences Health Sciences Campus, Kochi, 682 041, Kerala, India.
  • Chakravarty S; Applied Biology Division, CSIR- Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad, 500007, Telangana, India. sumanachak@iict.res.in.
Neuromolecular Med ; 23(4): 449-465, 2021 12.
Article em En | MEDLINE | ID: mdl-33948878
ABSTRACT
Based on the findings in recent years, we summarize the therapeutic potential of vorinostat (VOR), the first approved histone deacetylase (HDAC) inhibitor, in disorders of brain, and strategies to improve drug efficacy and reduce side effects. Scientific evidences provide a strong case for the therapeutic utility of VOR in various disorders affecting brain, including stroke, Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, X-linked adrenoleukodystrophy, epilepsy, Niemann-Pick type C disease, and neuropsychiatric disorders. Further elucidation of the neuroprotective and neurorestorative properties of VOR using proper clinical study designs could provide momentum towards its clinical application. To improve the therapeutic prospect, concerns on systemic toxicity and off-target actions need to be addressed along with the improvement in formulation and delivery aspects, especially with respect to solubility, permeability, and pharmacokinetic properties. Newer approaches in this regard include poly(ethylene glycol)-b-poly(DL-lactic acid) micelles, VOR-pluronic F127 micelles, encapsulation of iron complexes of VOR into PEGylated liposomes, human serum albumin bound VOR nanomedicine, magnetically guided layer-by-layer assembled nanocarriers, as well as convection-enhanced delivery. Even though targeting specific class or isoform of HDAC is projected as advantageous over pan-HDAC inhibitor like VOR, in terms of adverse effects and efficacy, till clinical validation, the idea is debated. As the VOR treatment-related adverse changes are mostly found reversible, further optimization of the therapeutic strategies with respect to dose, dosage regimen, and formulations of VOR could propel its clinical prospects.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Reposicionamento de Medicamentos / Ácidos Hidroxâmicos Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Reposicionamento de Medicamentos / Ácidos Hidroxâmicos Idioma: En Ano de publicação: 2021 Tipo de documento: Article