|
|
CC1=C(C=CC2=C1N=C(N2)[C@@]3(CCCN3C(=O)C4=C(C=CC(=C4)OC)N5N=CC=N5)C)Cl |
Approved |
|
Orexin Receptors OX1R and OX2R
|
Orexin Receptor Antagonism
|
Amodeo, L.R., Wills, D.N., Benedict, J. and Ehlers, C.L., 2025. Effects of daridorexant on rest/wake activity patterns and drinking in adult rats exposed to chronic ethanol vapor in adolescence. Alcohol, 124, pp.35-46.
|
|
|
C[C@]1(C2=C(CC(CC2=O)(C)C)NC3=NNC(=C31)C(F)(F)F)C4=CC=CC=C4 |
Not approved |
Period shortening in mammalian cells
|
GSK-3α/β
|
Selective GSK-3β Inhibition:,
Circadian Clock Impact
|
Wagner, F.F., Bishop, J.A., Gale, J.P., Shi, X., Walk, M., Ketterman, J., Patnaik, D., Barker, D., Walpita, D., Campbell, A.J. and Nguyen, S., 2016. Inhibitors of glycogen synthase kinase 3 with exquisite kinome-wide selectivity and their functional effects. ACS Chemical Biology, 11(7), pp.1952-1963.
|
|
|
C1C(=S)N(C2=C(C=C(C=C2)Cl)C(=N1)C3=CC=CC=C3F)CC(F)(F)F |
Approved |
|
GABAA receptors
|
GABAergic system influence
|
Hilbert, J.M., Chung, M., Maier, G., Gural, R., Symchowicz, S. and Zampaglione, N., 1984. Effect of sleep on quazepam kinetics. Clinical Pharmacology & Therapeutics, 36(1), pp.99-104.
|
|
|
C(C(Cl)(Cl)Cl)(O)O |
Not approved |
|
GABAA receptors
|
GABAergic system influence
|
Ashrafi, M.R., Mohammadi, M., Tafarroji, J., Shabanian, R., Salamati, P. and Zamani, G.R., 2010. Melatonin versus chloral hydrate for recording sleep EEG. european journal of paediatric neurology, 14(3), pp.235-238.
|
|
|
C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)CO)O)O)N |
Not approved |
|
ADORA2B
|
A2B receptor agonist.
|
Hinz, S., Lacher, S.K., Seibt, B.F. and Müller, C.E., 2014. BAY60-6583 acts as a partial agonist at adenosine A2B receptors. The Journal of pharmacology and experimental therapeutics, 349(3), pp.427-436.
|
|
|
CN1CCN(CC1)C(=O)OC2C3=NC=CN=C3C(=O)N2C4=NC=C(C=C4) Cl |
Approved |
|
GABAA receptors
|
GABA A receptor binding,
GABAergic system influence
|
Masse, M., Henry, H., Cuvelier, E., Pinçon, C., Pavy, M., Beeuwsaert, A., Barthélémy, C., Cuny, D., Gautier, S., Kambia, N. and Lefebvre, J.M., 2022, January. Sleep medication in older adults: identifying the need for support by a community pharmacist. In Healthcare (Vol. 10, No. 1, p. 147). MDPI.
|
|
|
CN(C)CCC=C1C2=CC=CC=C2COC3=CC=CC=C31.Cl |
Approved |
|
GABAA receptors
|
GABA A receptor binding,
GABAergic system influence
|
Yeung, W.F., Chung, K.F., Yung, K.P. and Ng, T.H.Y., 2015. Doxepin for insomnia: a systematic review of randomized placebo-controlled trials. Sleep medicine reviews, 19, pp.75-83.
|
|
|
CCCC(C)C1(C(=O)NC(=O)NC1=O)CC=C |
None |
|
GABAA receptors
|
GABA A receptor binding,
GABAergic system influence
|
Brunet, R., Caza, N. and Cyr, A., 1996. Food intake and circadian rhythms of activity of red-winged blackbirds (Agelaius phoeniceus). A time-course study on the effects of alpha-chloralose and secobarbital. Biological Rhythm Research, 27(2), pp.227-240.
|
|
|
CC1=NN=C2N1C3=C(C=C(C=C3)Cl)C(=NC2)C4=CC=CC=C4Cl |
Approved |
|
GABAA receptors
|
GABA A receptor binding,
GABAergic system influence
|
Seidel, W.F., Cohen, S.A., Bliwise, N.G., Roth, T. and Dement, W.C., 1986. Dose‐related effects of triazolam and flurazepam on a circadian rhythm insomnia. Clinical Pharmacology & Therapeutics, 40(3), pp.314-320.
,
Turek, F.W. and Losee-Olson, S.H., 1987. Dose response curve for the phase-shifting effect of triazolam on the mammalian circadian clock. Life sciences, 40(11), pp.1033-1038.
|
|
|
CCN(CC)CCN1C(=O)CN=C(C2=C1C=CC(=C2)Cl)C3=CC=CC=C3F |
Approved |
|
GABAA receptors
|
GABAergic system influence
|
Seidel, W.F., Cohen, S.A., Bliwise, N.G., Roth, T. and Dement, W.C., 1986. Dose‐related effects of triazolam and flurazepam on a circadian rhythm insomnia. Clinical Pharmacology & Therapeutics, 40(3), pp.314-320.
,
Crowley, T.J. and Hydinger-Macdonald, M., 1979. Bedtime flurazepam and the human circadian rhythm of spontaneous motility. Psychopharmacology, 62, pp.157-161.
|
|
|
CC1=C(C2=CC3=NC(=CC4=NC(=CC5=C(C(=C(N5)C=C1N2)C=C)C)C(=C4CCC(=O)O)C)C(=C3C)CCC(=O)O)C=C |
None |
|
CLOCK-BMAL1
|
Core clock modulation,
BMAL1 expression modulation
|
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.
|
|
|
COC1=C(C2=C[N+]3=C(C=C2C=C1)C4=CC5=C(C=C4CC3)OCO5)OC.[Cl-] |
Not approved |
|
CLOCK-BMAL1
,
REV-ERBα
,
Rev-erb expression
,
NLRP3 inflammasome
|
BMAL1 expression modulation,
Rev-erb expression modulation,
NLRP3 inflammasome 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.
,
Zhou, Z., Lin, Y., Gao, L., Yang, Z., Wang, S. and Wu, B., 2020. Circadian pharmacological effects of berberine on chronic colitis in mice: role of the clock component Rev-erbα. Biochemical pharmacology, 172, p.113773.
,
Ye, C., Zhang, Y., Lin, S., Chen, Y., Wang, Z., Feng, H., Fang, G. and Quan, S., 2023. Berberine ameliorates metabolic-associated fatty liver disease mediated metabolism disorder and redox homeostasis by upregulating clock genes: Clock and Bmal1 expressions. Molecules, 28(4), p.1874.
|
|
|
CN1CCN(CC1)/C=C\2/C(=O)N3C(=N2)CN=C(C4=C3C=CC(=C4)[N+](=O)[O-])C5=CC=CC=C5Cl |
Not approved |
|
GABAA receptors
|
GABA A receptor binding,
GABAergic system influence
|
De Crescenzo, F., D'Alò, G.L., Ostinelli, E.G., Ciabattini, M., Di Franco, V., Watanabe, N., Kurtulmus, A., Tomlinson, A., Mitrova, Z., Foti, F. and Del Giovane, C., 2022. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis. The Lancet, 400(10347), pp.170-184.
|
|
|
C1C(=O)NC2=C(C=C(C=C2)[N+](=O)[O-])C(=N1)C3=CC=CC=C3 |
Not approved |
|
GABAA receptors
|
GABA A receptor binding,
GABAergic system influence
|
Turek, F.W. and Van Reeth, O., 1989. Use of benzodiazepines to manipulate the circadian clock regulating behavioral and endocrine rhythms. Hormone Research in Paediatrics, 31(1-2), pp.59-65.
|
|
|
CN1C2=C(C=C(C=C2)Cl)C(=NC(C1=O)O)C3=CC=CC=C3Cl |
Not approved |
|
GABAA receptors
|
GABA A receptor binding,
GABAergic system influence
|
https://pubmed.ncbi.nlm.nih.gov/35052310/
|
|
|
C1=CC2=C(C=CC(=C2N=C1)O)[N+](=O)[O-] |
Approved |
|
BMAL1 expression (induction)
|
BMAL1 expression modulation
|
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.
|
|
|
CN(CCCOC1=C(C=C(C=C1)Cl)Cl)CC#C.Cl |
Approved |
|
CLOCK-BMAL1
,
Arntl (gene)
,
BMAL1 expression (induction)
,
Monoamine oxidase A
|
Bmal1,
de-repressing BMAL1,
BMAL1 expression modulation,
BMAL1 expression modulation,
Monoamine oxidase A 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.
|
|
|
CN1CC(CC2C1CC3=CN(C4=CC=CC2=C34)C)CNC(=O)OCC5=CC=CC=C5 |
Approved |
|
CLOCK-BMAL1
,
Arntl (gene)
,
BMAL1 expression (induction)
|
de-repressing BMAL1,
BMAL1 expression modulation,
BMAL1 expression modulation
|
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.
|
|
|
CC1CCC2=C3N1C=C(C(=O)C3=CC(=C2N4CCC(CC4)O)F)C(=O)O |
Approved |
|
CLOCK-BMAL1
|
Bmal1,
de-repressing BMAL1,
BMAL1 expression modulation,
BMAL1 expression modulation
|
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.
,
Jacob, H., Curtis, A.M. and Kearney, C.J., 2020. Therapeutics on the clock: circadian medicine in the treatment of chronic inflammatory diseases. Biochemical pharmacology, 182, p.114254.
|
|
|
C1=CC2=C(C(=C1)Cl)SC=C2COC(CN3C=CN=C3)C4=C(C=C(C=C4)Cl)Cl |
Approved |
|
CLOCK-BMAL1
,
Arntl (gene)
,
BMAL1 expression (induction)
|
BMAL1 expression modulation,
Myosin-9 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.
|
|
|
CC(=O)[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C)O |
Approved |
|
CLOCK-BMAL1
,
BMAL1 expression (induction)
,
Glyceraldehyde-3-phosphate dehydrogenase
|
Glyceraldehyde-3-phosphate dehydrogenase
|
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.
|
|
|
C[C@@H]1CC[C@H]2[C@H]([C@H](O[C@H]3[C@@]24[C@H]1CC[C@](O3)(OO4)C)O)C |
Approved |
|
BMAL1 expression (induction)
|
BMAL1 expression modulation,
"Peptidyl-prolyl cis-trans isomerase A Peroxiredoxin-1 60S ribosomal protein L10, L14, L18, L23a, L35, L4 40S ribosomal prote
|
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.
|
|
|
CC1C(C(CC(O1)OC2CC(CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=O)C)O)N)O.Cl |
Approved |
|
CLOCK-BMAL1
,
Arntl (gene)
,
BMAL1 expression (induction)
|
Bmal1,
de-repressing BMAL1,
BMAL1 expression modulation,
BMAL1 expression modulation,
DNA DNA topoisomerase 2-alpha, beta binding
|
|
|
|
CC1=CC(=C(C(=C1/C=C/C(=C/C=C/C(=C/C(=O)O)/C)/C)C)C)OC |
Approved |
|
CLOCK-BMAL1
,
Arntl (gene)
,
BMAL1 expression (induction)
|
Bmal1,
BMAL1 expression modulation,
BMAL1 expression modulation
|
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.
|
|
|
CC(C)CC1C(=O)N2CCCC2C3(N1C(=O)C(O3)(C(C)C)NC(=O)C4CN(C5CC6=C(NC7=CC=CC(=C67)C5=C4)Br)C)O |
Approved |
|
CLOCK-BMAL1
,
D2R (dopamine receptor)
,
BMAL1 expression (induction)
|
Dopamine receptor binding,
Bmal1,
de-repressing BMAL1,
Dopamine receptor binding,
Dopamine receptor agonist,
BMAL1 expression modulation,
BMAL1 expression modulation
|
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.
|