The discovery of 6-amino nicotinamides as potent and selective histone deacetylase inhibitors

Hamblett, Christopher L.; Methot, Joey L.; Mampreian, Dawn M.; Sloman, David L.; Stanton, Matthew; Kral, Astrid M.; Fleming, James E.; Cruz, Jonathan C.; Chénard, Mélissa; Ozerova, Nicole; Hitz, A.; Wang, Hongmei; Deshmukh, Sujal V.; Nazef, Naim; Harsch, Andreas; Hughes, Bethany; Dahlberg, William K.; Szewczak, Alex A.; Middleton, Richard E.; Mosley, Ralph T.; Secrist, J. Paul; Miller, Thomas A.

doi:10.1016/j.bmcl.2007.08.023

Cited by 44 publications

(30 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…And the exploration of nicotinamide core within benzamide HDAC inhibitors led to class I selective HDAC inhibitors. These had also been shown to demonstrate in vivo efficacy in a HCT116 xenograft model [214]. In addition to aforementioned, screening could be executed with targeted compound libraries.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…For instance, the study of 14A internal cavity adjacent to the enzyme catalytic site led to the discovery of a unique bis(aryl)-type pharmacophore. Using structural activity relationships (SARs), this lead was further optimized to produce hydroxamic acids that target HDAC 1 and 2 only [213,214]. And the exploration of nicotinamide core within benzamide HDAC inhibitors led to class I selective HDAC inhibitors.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…Investigations may be carried out on the HDAC enzyme itself, with the intent of structure based drug design (SBDD) [213,214]. For instance, the study of 14A internal cavity adjacent to the enzyme catalytic site led to the discovery of a unique bis(aryl)-type pharmacophore.…”

Section: Future Perspectivesmentioning

confidence: 99%

See 2 more Smart Citations

Histone Deacetylase Inhibitors: New Hope for Rheumatoid Arthritis?

Choo¹,

Ho²,

Lin

2008

CPD

View full text Add to dashboard Cite

Histone deacetylase (HDAC) inhibitors are a new family of anti-cancer agents currently undergoing clinical investigations for various oncology indications. Their anti-inflammatory activities had been well documented and they appear to be potential therapeutic strategies for various inflammatory diseases. In this review, the anti-inflammatory activities of HDAC inhibitors with emphasis on their potential applications in rheumatoid arthritis (RA) will be summarized. The possible anti-rheumatic mechanisms, including growth arrest in rheumatoid arthritis synovial fibroblasts (RASFs), suppression of pro-inflammatory cytokines or chemokines, anti-angiogenesis as well as protective effects on bone and cartilage destruction will also be discussed. Current literatures strongly imply HDAC inhibitors as innovative anti-rheumatic drug candidates. However, long-term safety is a major concern. Future investigations should focus on identification of molecular anti-rheumatic mechanisms, development of new classes of HDAC inhibitors with better safety and selectivity profiles, combination of HDAC inhibitors with disease modifying anti-rheumatic drugs (DMARDs) and establishment of topical or intra-articular formulations.

show abstract

Section: Future Perspectivesmentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

See 1 more Smart Citation

Histone Deacetylase Inhibitors: New Hope for Rheumatoid Arthritis?

Choo¹,

Ho²,

Lin

2008

CPD

View full text Add to dashboard Cite

show abstract

“…Interestingly, also SIRT inhibitors (SIRTi), the inhibitors of Sirtuins, class III HDACs Table 5 [216][217][218][219][220][221][222][223], whose relevance to cancer has been more recently US20090069301 [217] US20090099170 [218] US20090105246 [219] US20090105264 [220] US20090137681 [221] US20090143376 [222] US20090163476 [223] suggested [224] are starting to be proposed as tools to inhibit cancer growth, thus indicating that we are only at the initial phases of epigenetic-modulating therapy.…”

Section: Recent Patenting Of Hdacis Against Cancermentioning

confidence: 99%

Histone Deacetylase Inhibitors: Recent Insights from Basic to Clinical Knowledge & Patenting of Anti-Cancer Actions

Carafa

Nebbioso²,

Altucci³

2011

PRA

View full text Add to dashboard Cite

Epigenetic modiﬁcations have been causally linked to cancer development and progression, and are potentially reversible by drug treatments. The N-terminal tails of histones contain amino acid residues modiﬁable by post-translational modifications such as acetylation. Given that HDAC inhibitors induce cancer cell differentiation and death, an increasing number of these compounds has been synthesized in the last ten years. Many HDAC inhibitors are in clinical trials for the treatment of cancer. Two of them, the hydroxamic acid (SAHA) and Romidepsin (FK 228), are approved in the second line treatment of refractory, persistent or relapsed Cutaneous T Cell Lymphoma (CTCL). The growing evidence of the potential benefits of an anti-cancer treatment based on the use of HDAC inhibitors have led to a large number of patent applications all over the world. The aim of this review is to give an overview of the basic current knowledge and molecular mechanisms of HDAC inhibitors and their clinical trials as well as to focus on the recent patent applications existing in the field of HDAC inhibitors and cancer treatment between 2008 and 2010 in USA.

show abstract

“…The former group evolved their series of compounds from N-(2-aminophenyl) nicotinamide, a 12.4 mM screening hit [59]. The group rationalized that the 6-position of the pyridine could easily be functionalized and set about a rapid SAR exploration.…”

Section: Histone Deacetylase Inhibitors J201mentioning

confidence: 99%

Histone Deacetylase Inhibitors

Jones

2009

Epigenetic Targets in Drug Discovery

View full text Add to dashboard Cite

The discovery of 6-amino nicotinamides as potent and selective histone deacetylase inhibitors

Cited by 44 publications

References 36 publications

Histone Deacetylase Inhibitors: New Hope for Rheumatoid Arthritis?

Histone Deacetylase Inhibitors: New Hope for Rheumatoid Arthritis?

Histone Deacetylase Inhibitors: Recent Insights from Basic to Clinical Knowledge & Patenting of Anti-Cancer Actions

Histone Deacetylase Inhibitors

Contact Info

Product

Resources

About