1454903-06-0Relevant articles and documents
Synthesis and Pharmacological Evaluation of Selective Histone Deacetylase 6 Inhibitors in Melanoma Models
Tavares, Maurício T.,Shen, Sida,Knox, Tessa,Hadley, Melissa,Kutil, Zsófia,Ba?inka, Cyril,Villagra, Alejandro,Kozikowski, Alan P.
, p. 1031 - 1036 (2017)
Only a handful of therapies offer significant improvement in the overall survival in cases of melanoma, a cancer whose incidence has continued to rise in the past 30 years. In our effort to identify potent and isoform-selective histone deacetylase (HDAC) inhibitors as a therapeutic approach to melanoma, a series of new HDAC6 inhibitors based on the nexturastat A scaffold were prepared. The new analogues 4d, 4e, and 7b bearing added hydrophilic substituents, so as to establish additional hydrogen bonding on the rim of the HDAC6 catalytic pocket, exhibit improved potency against HDAC6 and retain selectivity over HDAC1. Compound 4d exhibits antiproliferative effects on several types of melanoma and lymphoma cells. Further studies indicates that 4d selectively increases acetylated tubulin levels in vitro and elicits an immune response through down-regulating cytokine IL-10. A preliminary in vivo efficacy study indicates that 4d possesses improved capability to inhibit melanoma tumor growth and that this effect is based on the regulation of inflammatory and immune responses.
SELECTIVE HISTONE DEACTYLASE 6 INHIBITORS
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Page/Page column 50, (2015/02/25)
Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula I. Specifically, the disclosed subject matter relates to compounds having activity as selective HDAC6 inhibitors, methods of making and using the compounds, and compositions comprising the compounds. In still further aspects, the disclosed subject matter relates to methods for treating oncological disorders in a patient. Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed.
