Table 3.

Experimental and clinical drugs acting on circadian pathway.

Drug	Mechanism of Action	Status	Ref.
Tasimelteon (Hetlioz)	Melatonin receptor agonist (MT1 and MT2); entrains the circadian clock in totally blind individuals with non-24-h sleep-wake disorder.	FDA-approved for non-24-h sleep-wake disorder.	Tsuey Tse (2014)
Melatonin	Agonist for melatonin receptors (MT1 and MT2); synchronizes circadian rhythms and regulates sleep-wake cycles.	Widely available; used off-label for circadian rhythm disorders.	(Tsuey Tse, 2014), (Ruan et al., 2021), (Tsuey Tse, 2014)
Modafinil/Armodafinil	Promotes wakefulness by modulating dopamine transporters; used for shift work sleep disorder.	FDA-approved for shift work disorder.	Servid (2021)
Nobiletin	ROR agonist; enhances circadian clock amplitude and metabolic protection in preclinical studies.	Under investigation in preclinical studies.	Ruan et al. (2021)
KL001	Stabilizes CRY; lengthens the circadian period and reduces amplitude.	Experimental; preclinical development.	Ruan et al. (2021)
CK1 Inhibitors	Stabilize PER proteins by inhibiting casein kinase 1 (CK1); modulate circadian period length.	Experimental; preclinical development.	Ruan et al. (2021)
REV-ERB Agonists	Target nuclear receptor REV-ERB to regulate circadian transcription and metabolism.	Under investigation in preclinical studies.	Sulli et al. (2018)
Ramelteon	Produces significant phase advance of human melatonin rhythm, facilitates resynchronization; melatonin agonist, decreases fibrosis severity	Under investigation in clinical studies.	(Richardson et al., 2008), (Aydin et al., 2023)
Agomelatine	Acts via non-selective MT1/MT2 melatonin receptor agonist, prevents oxidative stress, induces anti-inflammatory effects	Under investigation in clinical studies.	Promsan et al. (2022)
Tasimelteon	Melatonin receptor agonist with higher affinity for MT2 receptors, retrains circadian clock	FDA-approved treatment	Pavkovic and Kothare (2022)