What is chemical genomics?
Chemical genetics is is broadly defined as the study of biological processes using small-molecule intervention rather than genetic intervention. Chemical genomics is the extension of this study to the whole genome. This process combines genetics, chemistry, and biology to aid in understanding of how small molecules can be used to modulate protein function, gene expression, and cellular processes [1].
Chemical screens can be performed to test small molecules to treat cells in well plates. This can be done with one of two types of chemical libraries: diversity-based or target-focused. Diversity-based libraries are predominantly designed for targets with few known active chemotypes, whereas target-focused libraries are intended for well-studied targets [2].
Chemical screens can be performed to test small molecules to treat cells in well plates. This can be done with one of two types of chemical libraries: diversity-based or target-focused. Diversity-based libraries are predominantly designed for targets with few known active chemotypes, whereas target-focused libraries are intended for well-studied targets [2].
Compound for SCN1A
No compounds aside from siRNAs are found on PubChem when you search for SCN1A [3].
Further research into FHM3 shows promising pharmacological treatment in the form of late sodium current blocker GS967 [4].
Further research into FHM3 shows promising pharmacological treatment in the form of late sodium current blocker GS967 [4].
This compound is known to bind to Nav1.5, which is encoded by SCN5A. This study looked at the effects of GS967 on persistent current cause by SCN1A gain-of-function mutations in Xenopus. The promising results confirmed that GS967 binds directly to and interacts with the Nav1.1 protein, which is encoded by SCN1A [4].
Discussion
GS967 has been shown to bind to Nav1.1. There are currently calcium channel blockers that are used to prevent other types of FHM, but these do not work with FHM3 due to sodium influx being the issue [5]. A drug that can inhibit this influx of sodium into neurons may reduce occurrences of CSD, which could lead to reduced episodes of hemiplegia and migraine. Using this information, designing a target-focused library around GS967 to study rescue of symptoms is worth consideration.
References
[1] MacBeath, G. (2001). Chemical genomics: what will it take and who gets to play? Genome Biology, 2(6). https://doi.org/10.1186/gb-2001-2-6-comment2005
[2] Golub, A. (2020, January 28). Diversity-based Screening of Compound Libraries in Drug Discovery. Life Chemicals. https://lifechemicals.com/blog/computational-chemistry/diversity-based-screening-of-compound-libraries-in-drug-discovery
[3] U.S. National Library of Medicine. (n.d.). SCN1A search results. National Center for Biotechnology Information. PubChem Compound Database. https://pubchem.ncbi.nlm.nih.gov/#query=Scn1a&tab=substance
[4] Barbieri, R., Bertelli, S., Pusch, M., & Gavazzo, P. (2019). Late sodium current blocker GS967 inhibits persistent currents induced by familial hemiplegic migraine type 3 mutations of the SCN1A gene. The Journal of Headache and Pain, 20(1). https://doi.org/10.1186/s10194-019-1056-2
[5] Kuruvilla, D. (2023, August 25). What to Know About Familial Hemiplegic Migraine. Healthline. https://www.healthline.com/health/migraine/familial-hemiplegic-migraine#outlook
[2] Golub, A. (2020, January 28). Diversity-based Screening of Compound Libraries in Drug Discovery. Life Chemicals. https://lifechemicals.com/blog/computational-chemistry/diversity-based-screening-of-compound-libraries-in-drug-discovery
[3] U.S. National Library of Medicine. (n.d.). SCN1A search results. National Center for Biotechnology Information. PubChem Compound Database. https://pubchem.ncbi.nlm.nih.gov/#query=Scn1a&tab=substance
[4] Barbieri, R., Bertelli, S., Pusch, M., & Gavazzo, P. (2019). Late sodium current blocker GS967 inhibits persistent currents induced by familial hemiplegic migraine type 3 mutations of the SCN1A gene. The Journal of Headache and Pain, 20(1). https://doi.org/10.1186/s10194-019-1056-2
[5] Kuruvilla, D. (2023, August 25). What to Know About Familial Hemiplegic Migraine. Healthline. https://www.healthline.com/health/migraine/familial-hemiplegic-migraine#outlook
About the website
This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison
Joely Swanson
Last updated April 9th, 2024
Genetics 564 Website
Joely Swanson
Last updated April 9th, 2024
Genetics 564 Website