Tricyclic chemical modulators of FOXO transcription factor proteins are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and acne. The compounds are of the following phenothiazine, dibenzoazepine and annulene and similar genera: ##STR00001##

Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are triphenyl methane analogs. The compounds and compositions can be used to treat and/or prevent a wide variety of cancers, including drug resistant cancers, inflammatory, degenerative and vascular diseases, including various ocular diseases, and parasitic infections. Representative triphenyl methane analogs include triphenyl methane analogues of various dyes, hormones, sugars, peptides, oligonucleotides, amino acids, nucleotides, nucleosides, and polyols. The compounds are believed to function by inhibiting tNOX expression, the effects of ROS, and/or the production of HIF2. Thus, the compounds are novel therapeutic agents for a variety of cancers and other diseases.

The present disclosure belongs to the field of biomedicine, and specifically relates to a method for preventing or treating neurodegenerative diseases or alleviating symptoms of neurodegenerative diseases. Said method comprises administering an effective amount of a thiamine pyrophosphokinase (TPK) agonist to an individual in need of said agonist.

The present disclosure belongs to the field of biomedicine, and specifically relates to a method for preventing or treating neurodegenerative diseases or alleviating symptoms of neurodegenerative diseases. Said method comprises administering an effective amount of a thiamine pyrophosphokinase (TPK) agonist to an individual in need of said agonist.

The present disclosure provides compounds of Formula I, a free base form thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical compositions comprising the same, and methods of treating medical disorders using the same.

The present disclosure provides compounds of Formula I, a free base form thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical compositions comprising the same, and methods of treating medical disorders using the same.