circadian

(E/Z)-GO289, which strongly lengthened circadian period, is a potent and selective inhibitor of CK2. (E/Z)-GO289 exhibited cell type-dependent inhibition of cancer cell growth that correlated with cellular clock function. The discovery of (E/Z)-GO289 provides a direct link between the circadian clock and cancer regulation and reveals unique design principles underlying kinase selectivity.

KL 001 is a Cryptochrome protein (CRY) stabilizer. KL001 prevented ubiquitin-dependent degradation of CRY, resulting in lengthening of the circadian period. KL001-mediated CRY stabilization inhibited glucagon-induced gluconeogenesis in primary hepatocytes. KL001 thus provides a tool to study the regulation of CRY-dependent physiology and aid development of clock-based therapeutics of diabetes.

Tasimelteon (BMS-214778) is a melatonin receptor agonist that is used for the treatment of non-24 hour sleep-wake disorder in blind individuals.

KL201, a circadian clock modulator, is an isoform-selective cryptochrome 1 (CRY1) stabilizer that lengthens the period of circadian rhythms in cells and tissues [1].

Prolylleucine (((Benzyloxy)carbonyl)-L-prolyl-D-leucine) is a dipeptide containing branched-chain amino acids.

Betaine chloride (Betaine hydrochloride) is an acidic form of betaine, a vitamin-like substance observed in grains and other foods; gains the amplification of DNA by decreasing the formation of secondary structure in GC-rich regions.

1A-116 is a specific inhibitor of Rac1 .

Hesperin (6-MSITC), a flavonoid isolated from orange peel, is a circadian decapping enzyme in plants, inhibiting lipid accumulation and production of reactive oxygen and nitrogen species in 3T3-L1 and RAW264.7 cells.

TIK-301 is a chlorinated melatonin derivative and a potent, high-affinity, and orally active melatonin MT1 and MT2 receptors agonist (Kis: 0.081 nM and 0.042 nM, respectively). TIK-301 is also a 5-HT2B/5-HT2C receptor antagonist with antidepressant action. TIK-301 has the potential for sleep disorders and other circadian rhythm disorders treatment.

E3 Ligase Ligand-linker Conjugate 163 is the E3 ligase ligand (E3 Ligase Ligand 58)-linker conjugate component of AH078, a PROTAC that selectively degrades CK1δ and CK1ε. It is utilized in research related to circadian rhythm disorders.

GR 196429, a melatonin receptor agonist, exhibits selectivity for the MT1 subtype. This compound not only promotes sleep and alters circadian rhythms but also stimulates melatonin release in mice.

LY2033298, a positive allosteric modulator of muscarine M4 receptor, enhances the inhibitory effect of oximoline on light-induced phase shift in circadian activity in hamsters and can be used in neurosystem-related diseases.

KL044 is a cryptochrome 1 (CRY1) activator that prolongs circadian rhythms and inhibits PER2 activity. KL044 inhibits melanogenesis by inhibiting the cAMP/PKA/CREB pathway.

Epitalon is a synthetic tetrapeptide with anti-aging properties.1,2,3,4 Dietary administration of epitalon (0.00001% w/w) reduces levels of lipid peroxidation products in aged D. melanogaster tissue homogenates.1 Epitalon (1 μg/animal) delays age-related estrous shutdown and decreases the frequency of bone marrow cell chromosomal aberrations in female mice.2 It decreases spontaneous mammary gland and ovarian tumor development and metastasis in aged female mice.3 Epitalon also stimulates melatonin synthesis and normalizes the circadian rhythm of cortisol secretion in senescent female M. mulatta monkeys.4References1. Khavinson, V.K., and Myl'nikov, S.V. Effect of epithalone on the age-specific changes in the time course of lipid peroxidation in Drosophila melanogaster. Bull. Exp. Biol. Med. 130(11), 1116-1119 (2000).2. Anisimov, V.N., Khavinson, V.K., Popovich, I.G., et al. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology 4(4), 193-202 (2003).3. Kossoy, G., Anisimov, V.N., Ben-Hur, H., et al. Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice. In Vivo 20(2), 253-257 (2006).4. Khavinson, V., Goncharova, N., and Lapin, B. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuro. Endocrinol. Lett. 22(4), 251-254 (2001). Epitalon is a synthetic tetrapeptide with anti-aging properties.1,2,3,4 Dietary administration of epitalon (0.00001% w/w) reduces levels of lipid peroxidation products in aged D. melanogaster tissue homogenates.1 Epitalon (1 μg/animal) delays age-related estrous shutdown and decreases the frequency of bone marrow cell chromosomal aberrations in female mice.2 It decreases spontaneous mammary gland and ovarian tumor development and metastasis in aged female mice.3 Epitalon also stimulates melatonin synthesis and normalizes the circadian rhythm of cortisol secretion in senescent female M. mulatta monkeys.4 References1. Khavinson, V.K., and Myl'nikov, S.V. Effect of epithalone on the age-specific changes in the time course of lipid peroxidation in Drosophila melanogaster. Bull. Exp. Biol. Med. 130(11), 1116-1119 (2000).2. Anisimov, V.N., Khavinson, V.K., Popovich, I.G., et al. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology 4(4), 193-202 (2003).3. Kossoy, G., Anisimov, V.N., Ben-Hur, H., et al. Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice. In Vivo 20(2), 253-257 (2006).4. Khavinson, V., Goncharova, N., and Lapin, B. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuro. Endocrinol. Lett. 22(4), 251-254 (2001).

SR9009 (Stenabolic), a REV-ERB agonist, increases the constitutive repression of genes regulated by REV-ERBα/ERBβ (IC50: 670/800 nM). Through activation of REV-ERB, SR9009 can decrease circadian locomotor activity during the dark phase and alter the expression pattern of core clock genes in the hypothalami of mice. The circadian pattern of expression of an array of metabolic genes in the liver, skeletal muscle, and adipose tissue was also altered in mice exposed to SR9009, resulting in increased energy expenditure. In Diet-induced obese mice, SR9009 (100 mg/kg, i.p., b.i.d., for 30 days) could decrease fat mass and markedly improve dyslipidemia and hyperglycemia.

KS15 is a cryptochrome (CRY) inhibitor that promotes G1 cell cycle arrest, enhances drug sensitivity in MCF-7 cells, and exhibits antitumour activity against human breast cancer cells.

FT709 is a selective USP9X deubiquitinating enzyme inhibitor (IC50=82 nM) that reduces Makorin and ZNF598 levels, impairing ribosomal quality control pathways.

Brevicompanine B is a fungal metabolite that has plant growth and circadian rhythm regulatory activity. Brevicompanine B inhibits primary root growth in Arabidopsis seedlings and disrupts the transcription of various genes involved in the regulation of plant circadian rhythm. It is active against P. falciparum.

CLK8 is a selective CLOCK inhibitor that binds to and interferes with CLOCK activity, disrupts the interaction between CLOCK and BMAL1, and modulates circadian rhythm amplitude.CLK8 can be used to study circadian rhythm-related disorders.

VU661, a redox-active phenazine carboxamide, modulates circadian rhythms by inducing period lengthening.

Delta (Phospho) Sleep Inducing Peptide (DSIP-P), a peptide that promotes sustained sleep, induces changes in circadian locomotor activity in rats [1][2][3].

Jujubosides have hypnotic effect on normal rats, may be influenced by circadian rhythm and the serotonergic system may involve in the hypnotic effect of jujubosides, jujubosides may be good source of lead compounds for novel hypnotics.

Potent, endogenous neuromedin U receptor agonist (EC50 values are 65 and 91 pM at NMU1 and NMU2 respectively). Induces phase shifts in the circadian rhythm of locomotor activity following i.c.v. administration. Potent endogenous anorexigenic peptide.

Neuropeptide Y (NPY) is a 36-amino acid neuropeptide that exerts its activity via G-protein-coupled receptors. NPY is widely distributed in the peripheral and central nervous systems. It modulates a variety of physiological processes, e.g. the central reg