Biology:Martinostat
Martinostat is a histone deacetylase (HDAC) inhibitor which is used in scientific research.[1][2]
| Enzyme | IC50 (nM) |
|---|---|
| HDAC1 | 0.3 |
| HDAC2 | 0.8–2.0 |
| HDAC3 | 0.6 |
| HDAC4 | 1,970 |
| HDAC5 | 352 |
| HDAC6 | 4.1 |
| HDAC7 | >20,000 |
| HDAC8 | >15,000 |
| HDAC9 | >15,000 |
| HDAC10 | ND |
| HDAC11 | ND |
| Refs: [1][2] | |
It is potent against recombinant class I HDACs (HDAC1, HDAC2, HDAC3) and class IIb HDAC (HDAC6) with low nanomolar affinities.[2] In tissue CETSA assays,[3] martinostat exhibits selectivity for class I HDACs.[4]
Unlike many other HDAC inhibitors, like vorinostat and givinostat, which show poor brain penetrance and only subtle brain HDAC inhibition, martinostat is highly lipophilic due to its adamantyl group and shows robust brain uptake.[1][2] When tagged with the radioisotope carbon-11, martinostat can be used to quantify HDAC in the brain and peripheral organs using positron emission tomography (PET) imaging.
Martinostat was first described in the scientific literature by 2014.[1][2] It was given a name that adopted the style of other HDAC inhibitors, such as vorinostat, entinostat, and crebinostat, that recognized the academic center in which it was developed, the Martinos Center for Biomedical Imaging.
See also
References
- ↑ 1.0 1.1 1.2 1.3 "PET imaging demonstrates histone deacetylase target engagement and clarifies brain penetrance of known and novel small molecule inhibitors in rat". ACS Chem Neurosci 5 (10): 1055–1062. October 2014. doi:10.1021/cn500162j. PMID 25188794. "Quantification of dynamic imaging data revealed that the hydroxamates SAHA and givinostat both resulted in only subtle blockade of radiotracer binding in whole brain (Figure 3A), consistent with recent reports demonstrating poor brain penetrance of the prototypical hydroxamic acid HDAC inhibitor, SAHA.14,15 Poor brain penetrance was overcome in the development of martinostat by the addition of an adamantyl group, a chemical moiety frequently used developing in CNS-penetrant compounds.10".
- ↑ 2.0 2.1 2.2 2.3 2.4 "In vivo imaging of histone deacetylases (HDACs) in the central nervous system and major peripheral organs" (in EN). Journal of Medicinal Chemistry 57 (19): 7999–8009. October 2014. doi:10.1021/jm500872p. PMID 25203558.
- ↑ "The cellular thermal shift assay for evaluating drug target interactions in cells". Nature Protocols 9 (9): 2100–22. September 2014. doi:10.1038/nprot.2014.138. PMID 25101824.
- ↑ "Insights into neuroepigenetics through human histone deacetylase PET imaging". Science Translational Medicine 8 (351): 351ra106. August 2016. doi:10.1126/scitranslmed.aaf7551. PMID 27510902.
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