Tianeptinaline is a histone deacetylase (HDAC) inhibitor which was derived via structural modification of the tricyclic antidepressant (TCA) tianeptine.
Pharmacology + Activities Enzyme (nM) HDAC1 240 HDAC2 120 HDAC3 155 HDAC4 HDAC5 >80,000 HDAC6 >80,000 HDAC7 HDAC8 HDAC9 HDAC10 HDAC11 Refs:
Tianeptinaline potently inhibits the class I HDAC1, HDAC2, and HDAC3 with values of 240nM, 120nM, and 155nM, whereas it did not inhibit the class II HDAC5 or HDAC6 ( = >80,000nM). Potential actions against other HDACs, such as HDAC4, HDAC7, HDAC8, and HDAC9, were not described. The drug has been found to enhance CREB-mediated transcription, penetrate into the brain, and enhance contextual fear conditioning, a behavioral measure of hippocampus-dependent memory, in rodents.
Chemistry The chemical synthesis of tianeptinaline has been described. Another analogue of tianeptinaline, known as tianeptinostat, is also a potent HDAC inhibitor. However, whereas tianeptinaline did not inhibit HDAC6, tianeptinostat was a highly potent inhibitor of HDAC6 in addition to the class I HDACs.
History Tianeptinaline and tianeptinostat were first described in the scientific literature by 2018. They were derived from tianeptine after it was noted that tianeptine has a similar chemical structure to that of the potent clinically used HDAC inhibitor vorinostat (SAHA) and that tianeptine itself is a weak HDAC inhibitor ( = 25,000nM, 82,000nM, and >2mM at HDAC1, HDAC2, and HDAC3, respectively).
See also Histone deacetylase inhibitor Tianeptine Tacedinaline Estianeptine
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