Intro:
Crebinostat is a novel HDAC inhibitor, capable of upregulating gene transcription within the brain via selective inhibition of various class I and II HDACs (see study 1). This indirectly increases gene transcription/expression within the brain, potentially yielding positive effects on overall cognition via an improvement on memory and neuroplasticity.
What even is an HDAC? (How HDACs work and the benefits of their inhibition):
HDACs (histone deacetylases) are enzymes primarily responsible for reducing gene expression/transcription indirectly. This process involves the removal of an acetyl group (deacetylation) from histones (basic proteins) which are bound to the DNA. This removal of the acetyl group allows the histones to bind more tightly to the DNA, physically blocking other proteins, namely transcription factors and RNA polymerase, from binding to said DNA and carrying out transcription. Basically, HDACS cause regulatory proteins (histones) to become more tightly bound to DNA, preventing other proteins (transcription factors) from binding to said DNA and carrying out gene transcription. By inhibiting HDACs, you're able to do the inverse; increase gene transcription and thus expression (study 2).
Potential Use of Crebinostat:
This drug has shown particular efficacy with increasing transcription activity attributed to the CREB transcription factor (study 1), which is linked with increased neuroplasticity, neural development, cell differentiation, and cell longevity (study 3). This aligns with the primary effects seen in vitro and in mice (study 1). However, this drug remains experimental, with virtually 0 human testing and no known practical dosage. It's safe to assume that, like most neurotrophic agents, this compound would primarily affect neuro and synaptogenesis within the hippocampus, mainly facilitating memory formation and emotional regulation.
2. https://pubmed.ncbi.nlm.nih.gov/23294310/
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC3691692/
birthdefect, I personally think NSI-189 mogs simply because of the human testing and more abundant literature surrounding it. However, NSI and Crebinostat work through different mechanisms, with NSI increasing the secretion of growth factors, while Crebinostat functions to make growth factors more effective via HDAC inhibition (there's a lot more nuance here). From my understanding, I theorize that they might even have synergy, with one making transcription easier (via HDAC inhibition), while the other increases secretion of relevant growth factors.
Crebinostat is a novel HDAC inhibitor, capable of upregulating gene transcription within the brain via selective inhibition of various class I and II HDACs (see study 1). This indirectly increases gene transcription/expression within the brain, potentially yielding positive effects on overall cognition via an improvement on memory and neuroplasticity.
What even is an HDAC? (How HDACs work and the benefits of their inhibition):
HDACs (histone deacetylases) are enzymes primarily responsible for reducing gene expression/transcription indirectly. This process involves the removal of an acetyl group (deacetylation) from histones (basic proteins) which are bound to the DNA. This removal of the acetyl group allows the histones to bind more tightly to the DNA, physically blocking other proteins, namely transcription factors and RNA polymerase, from binding to said DNA and carrying out transcription. Basically, HDACS cause regulatory proteins (histones) to become more tightly bound to DNA, preventing other proteins (transcription factors) from binding to said DNA and carrying out gene transcription. By inhibiting HDACs, you're able to do the inverse; increase gene transcription and thus expression (study 2).
Potential Use of Crebinostat:
This drug has shown particular efficacy with increasing transcription activity attributed to the CREB transcription factor (study 1), which is linked with increased neuroplasticity, neural development, cell differentiation, and cell longevity (study 3). This aligns with the primary effects seen in vitro and in mice (study 1). However, this drug remains experimental, with virtually 0 human testing and no known practical dosage. It's safe to assume that, like most neurotrophic agents, this compound would primarily affect neuro and synaptogenesis within the hippocampus, mainly facilitating memory formation and emotional regulation.
Papers used:
1. https://pubmed.ncbi.nlm.nih.gov/22771460/2. https://pubmed.ncbi.nlm.nih.gov/23294310/
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC3691692/
Closing statements:
Thanks for reading, I hope you found this topic as interesting as I did. This drug is still highly experimental, so it may not be as practical as other compounds out there. Additionally, I'm no doctor so please do your own research!! Lastly, to answer your question,
birthdefect, I personally think NSI-189 mogs simply because of the human testing and more abundant literature surrounding it. However, NSI and Crebinostat work through different mechanisms, with NSI increasing the secretion of growth factors, while Crebinostat functions to make growth factors more effective via HDAC inhibition (there's a lot more nuance here). From my understanding, I theorize that they might even have synergy, with one making transcription easier (via HDAC inhibition), while the other increases secretion of relevant growth factors. 
