Logo

List of Chronobiotics



Name SMILES FDA Status Effects Targets Mechanisms Articles
CN1[C@@H]2CC(C[C@H]1[C@H]3[C@H]2O3)OC(=O)[C@H](CO)C4=CC=CC=C4 Approved can disrupt circadian rhythms, can influence various aspects of sleep and wakefulness, including sleep onset, delta sleep, an Muscarinic acetilcholine receptror M1 Affects melatonin synthesis, Muscarinic receptor binding Abdel-Rahman, M., Abdel-Kader, S., El-Masry, H. and El-Hennamy, R.E., 2020. Light exposure during late night attenuates the risk of scopolamine-induced Alzheimer disease in aged rats. Egyptian journal of basic and applied sciences, 7(1), pp.126-140.
COC1=C(C=CC(=C1)C(=O)O)O Not approved Increases amplitude of circadian rhtyhms, Decreases phase MTOR (Human) , AMPK , JAC (Janus kinase) mTOR signaling inhibition, Serine/threonine-protein kinase mTOR, AMPK-PP2A axis suppresses mTOR, advancing circadian phase in muscle., Adenosine Monophosphate-Activated Protein Kinase (AMPK), Nuclear Factor Kappa B (NF- κB), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), Nod-like receptor family protein (NLRP), Toll-like receptors (TLRs), Mitogen-Activated Signaling Proteins (MAPK), Mammalian Target of Rapamycin (mTOR) signaling pathway Huang, J.Q., Lu, M. and Ho, C.T., 2021. Health benefits of dietary chronobiotics: beyond resynchronizing internal clocks. Food & Function, 12(14), pp.6136-6156. , Bhavani, P., Subramanian, P. and Shanmugapriya, S., 2016. Modulating effects of vanillic acid on circadian pattern of indices of redox homeostasis in N-Methly-N′-Nitro-N-Nitrosoguanidine induced endometrial carcinoma in rats. Biological Rhythm Research, 47(4), pp.609-619. , Kiessig, R.S., Herz, J.M. and Sweeney, B.M., 1979. Shifting the phase of the circadian rhythm in bioluminescence in Gonyaulax with vanillic acid. Plant Physiology, 63(2), pp.324-327. , Lashgari, N.A., Roudsari, N.M., Momtaz, S., Abdolghaffari, A.H., Atkin, S.L. and Sahebkar, A., 2023. Regulatory mechanisms of vanillic acid in cardiovascular diseases: a review. Current Medicinal Chemistry, 30(22), pp.2562-2576.
C1 =CC(=CC=C1C(=O)NC2=CC=C(C=C2)C(C(F)(F)F)(C(F)(F)F)O)C(F)(F)F none enhancing the expression of the core clock component BMAL1 BMAL1 expression (induction) BMAL1 expression modulation, p53 stabilization and apoptosis induction Rahman S, Wittine K, Sedic M, Markova-Car EP (2020) Small molecules Targeting Biological clock; a novel prospective for anti-cancer drugs. Molecules. ;25(21); doi: ARTN 493710.3390/molecules25214937.
COC1=C(C=C(C(=C1)/C=N\N2C(=NN=C2SC)C3=CC=CC=C3)Br)O not approved disrupts the circadian clock specifically in cancer cells CK2 alpha CK2 inhibition Oshima, T., Niwa, Y., Kuwata, K., Srivastava, A., Hyoda, T., Tsuchiya, Y., Kumagai, M., Tsuyuguchi, M., Tamaru, T., Sugiyama, A. and Ono, N., 2019. Cell-based screen identifies a new potent and highly selective CK2 inhibitor for modulation of circadian rhythms and cancer cell growth. Science advances, 5(1), p.eaau9060.
C[C@H]1C[C@@H]([C@@H]([C@H](/C=C(/[C@@H]([C@H](/C=C\C=C(\C(=O)NC2=CC(=O)C(=C(C1)C2=O)NCCN(C)C)/C)OC)OC(=O)N)\C)C)O)OC none via HSP90 affects the stability of BMAL1 and circadian gene expression. HSP90 HSP90 Binding, HSP90-mediated BMAL1 modulation Lee, Y., Fong, S.Y., Shon, J., Zhang, S.L., Brooks, R., Lahens, N.F., Chen, D., Dang, C.V., Field, J.M. and Sehgal, A., 2021. Time-of-day specificity of anticancer drugs may be mediated by circadian regulation of the cell cycle. Science advances, 7(7), p.eabd2645. , Schneider, R., Linka, R.M. and Reinke, H., 2014. HSP90 affects the stability of BMAL1 and circadian gene expression. Journal of Biological Rhythms, 29(2), pp.87-96.
C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)OC[C@@H]2[C@H]([C@@H]([C@H]([C@@H](O2)OC3=CC(=C4C(=O)C[C@H](OC4=C3)C5=CC(=C(C=C5)OC)O)O)O)O)O)O)O)O none Increases amplitude of circadian rhtyhms, reverses phase delay Per2 expression protect, PER gene exspression modulation, caspase, Bax, TNF-α, and NF-MB, Antioxidant Manjula, A., Subashini, R., Punitha, R. and Subramanian, P., 2017. Modulating effects of hesperidin on circadian pattern indices of rotenone induced redox homeostasis in clock mutant (cry b) of Drosophila melanogaster. Biological Rhythm Research, 48(6), pp.897-906. , Tayal, R., Munjal, K., Gauttam, V.K., Popli, P., Khurana, L. and Choudhary, N., 2023. Potential role of hesperidin in lifestyle disorders: A scoping review. South African Journal of Botany, 161, pp.542-554. , Jayapalan, J.J., Subramanian, P., Kani, A., Hiji, J., Najjar, S.G., Abdul‐Rahman, P.S. and Hashim, O.H., 2020. Hesperidin modulates the rhythmic proteomic profiling in Drosophila melanogaster under oxidative stress. Archives of Insect Biochemistry and Physiology, 105(3), p.e21738.
C1=CC(=CC=C1C2=COC3=C(C2=O)C=CC(=C3[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)CO)O)O)O)O)O none restores normal circadian rhythms, increased the expression levels of REV-ERBα target genes Bhmt, Cbs and Cth REV-ERBα Agonist REV-ERB alpha Chen, M., Zhou, C., Xu, H., Zhang, T. and Wu, B., 2020. Chronopharmacological targeting of Rev-erbα by puerarin alleviates hyperhomocysteinemia in mice. Biomedicine & pharmacotherapy, 125, p.109936. , Liu, J., Xu, H., Zhang, L., Wang, S., Lu, D., Chen, M. and Wu, B., 2021. Chronoeffects of the herbal medicines Puerariae radix and Coptidis rhizoma in mice: A potential role of REV-ERBα. Frontiers in Pharmacology, 12, p.707844.
CC1=CC2=C(C(=C1)O)C(=O)C3=C(C2=O)C=C(C=C3O)OC Not approved restores normal circadian rhythms, upregulate core circadian genes and reverse circadian misalignment caused by ethanol in liver cells. CLOCK-BMAL1 Bmal1, BMAL1 expression modulation, Interferes with CLOCK–BMAL1 Yao, Y., Zuo, A., Deng, Q., Liu, S., Zhan, T., Wang, M., Xu, H., Ma, J. and Zhao, Y., 2020. Physcion protects against ethanol-induced liver injury by reprogramming of circadian clock. Frontiers in Pharmacology, 11, p.573074. , Huang, J.Q., Lu, M. and Ho, C.T., 2021. Health benefits of dietary chronobiotics: beyond resynchronizing internal clocks. Food & Function, 12(14), pp.6136-6156.
C1=C(C=C(C(=C1O)O)O)C2=C(C(=O)C3=C(C=C(C=C3O2)O)O)O none Night alertness, Melatonin level reduction Serotonin N-acetyltransferase inhibition of serotonin N-acetyltransferase Shin, J.C., Jung, H.Y., Harikishore, A., Kwon, O.D., Yoon, H.S., Kim, K.T. and Choi, B.H., 2013. The flavonoid myricetin reduces nocturnal melatonin levels in the blood through the inhibition of serotonin N-acetyltransferase. Biochemical and biophysical research communications, 440(2), pp.312-316.
COC1=C(C=CC(=C1)/C=C/C(=O)CC(=O)/C=C/C2=CC(=C(C=C2)O)OC)O none Phase-dependent cell death modulation Per2 expression Per2 expression induction Sarma, A., Sharma, V.P., Sarkar, A.B., Sekar, M.C., Samuel, K. and Geusz, M.E., 2016. The circadian clock modulates anti-cancer properties of curcumin. BMC cancer, 16, pp.1-13.
C1=CC=C(C=C1)C2=CC(=O)C3=C(O2)C=C(C(=C3O)O)O none BMAL1 amplitude enhancement via RORα-dependent pathway. RORA , RORα ROR Sulaimani, N., Houghton, M.J., Bonham, M.P. and Williamson, G., 2024. Effects of (Poly) Phenols on Circadian Clock Gene–Mediated Metabolic Homeostasis in Cultured Mammalian Cells: A Scoping Review. Advances in Nutrition, 15(6), p.100232. , Paul, A., Das, P., Gogoi, M., Islam, M.A., Das, S. and Zaman, M.K., 2024. Baicalein: multiple pharmacological activities, pharmacokinetics, and clinical trials. Revista Brasileira de Farmacognosia, pp.1-15.
C1=CC(=C(C=C1C2=C(C(=O)C3=C(O2)C=C(C=C3)O)O)O)O none restores normal circadian rhythms, increased protein expression of the core clocks BMAL1 and CLOCK CLOCK-BMAL1 , BMAL1 , CLOCK-BMAL1 COMPLEX Bmal1, Interferes with CLOCK–BMAL1 Sulaimani, N., Houghton, M.J., Bonham, M.P. and Williamson, G., 2024. Effects of (Poly) Phenols on Circadian Clock Gene–Mediated Metabolic Homeostasis in Cultured Mammalian Cells: A Scoping Review. Advances in Nutrition, 15(6), p.100232. , Zhang, R., Liu, M., Lu, J., Lu, S., Wang, Y. and Guan, S., 2024. Fisetin Ameliorates Hepatocyte Lipid Droplet Accumulation via Targeting the Rhythmic Protein BMAL1 to Regulate Cell Death-Inducing DNA Fragmentation Factor-α-like Effector C-Mediated Lipid Droplet Fusion. Journal of Agricultural and Food Chemistry, 72(48), pp.26884-26897.
CC12CCC(=O)C=C1C3CC3C4C2CCC5(C4C6CC6C57CCC(=O)O7)C Approved CLOCK-BMAL1 , Arntl (gene) , BMAL1 expression (induction) Bmal1, de-repressing BMAL1, BMAL1 expression modulation, BMAL1 expression modulation, Mineral corticoid receptor binding Tamai, T.K., Nakane, Y., Ota, W., Kobayashi, A., Ishiguro, M., Kadofusa, N., Ikegami, K., Yagita, K., Shigeyoshi, Y., Sudo, M. and Nishiwaki‐Ohkawa, T., 2018. Identification of circadian clock modulators from existing drugs. EMBO molecular medicine, 10(5), p.e8724.
C1=CC(=CC=C1C2=COC3=CC(=CC(=C3C2=O)O)O)O none phase advance GSK-3α/β Highly selective, ATP-competitive inhibition of GSK-3 (both α and β isoforms), GSK‑3 Inhibition, Selective GSK-3β Inhibition:, inhibits glycogen synthase kinase-3β (GSK-3β) Sulaimani, N., Houghton, M.J., Bonham, M.P. and Williamson, G., 2024. Effects of (Poly) Phenols on Circadian Clock Gene–Mediated Metabolic Homeostasis in Cultured Mammalian Cells: A Scoping Review. Advances in Nutrition, 15(6), p.100232. , Zhou, L., Xiao, X., Zhang, Q., Zheng, J., Li, M., Yu, M., Wang, X., Deng, M., Zhai, X., Li, R. and Liu, J., 2019. Dietary genistein could modulate hypothalamic circadian entrainment, reduce body weight, and improve glucose and lipid metabolism in female mice. International Journal of Endocrinology, 2019(1), p.2163838.