turnover

Alendronic Acid (alendronate) is a nonhormonal medication used for osteoporosis, osteogenesis imperfecta, and several other bone diseases.

β-Gentiobiose is a natural oligosaccharide that promotes fruit ripening.

L-692429 (MK-0751) is a potent nonpeptidyl growth hormone secretagogue (GHS) agonist and benzolactam derivative, known for reversing glucocorticoid-induced inhibition of GH secretion. L-692429 exhibits high affinity for the G protein-coupled receptor and is useful in studying acromegaly and obesity.

Etidronic acid (HEDP) is a diphosphonate which affects calcium metabolism. It inhibits ectopic calcification and slows down bone resorption and bone turnover.

Pentabromophenol (NSC-5717) suppressed TGF-β response by accelerating the turnover rate of TGF-β receptors.

Cholestenone is an intermediate oxidation product of cholesterol that is metabolized primarily in the liver. It can cause long-term defects in cell function. It is highly mobile in membranes and affects cholesterol turnover and efflux.

1. β-Anhydroicaritin exhibits immunosuppressive effect on the mouse macrophages stimulated by LPS. 2. β-Anhydroicaritin phytosomes can inhibit enhanced bone turnover induced by ovariectomy, improve BMD the biomechanical properties of vertebrae, without any stimulation on uterus. 3. β-Anhydroicaritin possesses significant protective effects on the zymosan-induced peritonitis mice, which might be associated with the regulation of Ca(2+); influx in macrophages and iNOS expression.

KM02894 is a glutamate release inhibitor. Cancer cells release high levels of glutamate that can disrupt normal bone turnover, which can lead to cancer-induced bone pain.KM02894 may be used in the study of tumor-related diseases.

CLP257 is a selective K+-Cl− cotransporter KCC2 activator (EC50: 616 nM) and it is inactive against NKCC1, GABAA receptors, KCC1, KCC3 or KCC4. CLP257 alleviates hypersensitivity in rats with neuropathic painc and it also modulates plasmalemmal KCC2 protein turnover post-translationally. CLP257 restores impaired Cl− transport in neurons with diminished KCC2 activity.

RGH-5526 is a novel antihypertensive drug. It causes an increase in hypothalamic norepinephrine (NA) turnover (utilization), and the increase in hypothalamic noradrenergic neuron activity may lead to a decrease in peripheral sympathetic nerve activity, resulting in a significant reduction in blood pressure.

Lactacystin is an orally active, irreversible, and cell-permeable proteasome inhibitor (IC50 = 4.8 μM) that also inhibits the lysosomal enzyme cathepsin A. It induces apoptosis and cell cycle arrest, possesses anticancer, antiviral, and antioxidant activities, can penetrate the blood-brain barrier, and is commonly used in the construction of Parkinson’s disease and dementia models.

Sulbactam (CP45899) is a semi-synthetic beta-lactamase inhibitor. The beta-lactam ring of sulbactam irreversibly binds to beta-lactamase at or near its active site, thereby blocking enzyme activity and preventing metabolism of other beta-lactam antibiotics by the enzyme. Combining this agent with a beta-lactamase susceptible antibiotic, such as penicillins or a cephalosporin, to treat infections caused by beta-lactamase producing organisms, results in a decreased turnover rate of the beta-lactamase sensitive antibiotic and enhances its antibacterial activity.

Balicatib (AAE581) is a potent and selective inhibitor of cathepsin K, used in trials studying the treatment of osteoporosis.

PF-06273340 is an effective, Selective, and Peripherally Restricted Pan-Trk inhibitor (IC50: Trk-A = 6 nM; Trk-B = 4 nM; Trk-C = 3 nM). PF-06273340 has low metabolic turnover in HLM and hHep is a good substrate for efflux transporters P-gp (ER = 35.7) and BCRP (ER = 4.0) and has moderate passive permeability (RRCK Papp = 5.4 × 10 6 cm s 1).

Dehydroindapamide, an indole form of Indapamide, is utilized to quantify the turnover rate of Indapamide in CYP3A4, which is approximately 10 times higher than that of Indoline, with slightly enhanced affinity for CYP3A4.

L-654284 is an α2-adrenergic receptor antagonist characterized by its notable selectivity. It competes with 3H-clonidine and 3H-rauwolscine for binding in vitro, exhibiting Ki values of 0.8 nM and 1.1 nM, respectively. L-654284 effectively blocks the pre-ejaculatory effects of clonidine in isolated rat vas deferens, with a pA2 value of 9.1. The compound demonstrates significant selectivity for α2 over α1 adrenergic receptors, with a Ki value of 110 nM against 3H-prazosin binding. In vivo, L-654284 significantly increases the turnover of norepinephrine in the rat cerebral cortex, indicating its activity in blocking α2-adrenergic receptors within the central nervous system.

BNN27 is an agonist of the TrkA receptor (TrkAreceptor) and the p75NTR receptor (p75NTR receptor), exhibiting neurotrophic and anti-apoptotic properties. It enhances levels of glutamate, GABA, and glutamine in the hippocampus and prefrontal cortex of rats, improving glutamate turnover. In a mouse model of amyotrophic lateral sclerosis (ALS), BNN27 demonstrates neuroprotective effects, shows anti-inflammatory properties in an experimental autoimmune encephalomyelitis (EAE) model, and exhibits retinal protection in a rat diabetes model. BNN27 also possesses blood-brain barrier permeability.

RG-15 is an orally active dopamine receptor antagonist with high affinity for the human D2 receptor (pKi of 8.23) and human D3 receptor (pKi of 10.49). It inhibits dopamine-stimulated [35S]GTPγS binding with IC50 values of 21.2 nM in rat striatal membranes, 36.7 nM in mouse A9 cells expressing human D2L receptors, and 7.2 nM in CHO cells expressing human D3 receptors. RG-15 enhances dopamine turnover and synthesis in the striatum and olfactory bulb of mice, exhibiting antipsychotic activity.

AL-34662 (formate) is a 5-HT2 receptor agonist with an IC50 of 0.8-1.5 nM. It stimulates phosphoinositol turnover and Ca2+ release in human ciliary muscle cells (h-CM) with an E50 of 289 nM and in human trabecular meshwork cells (h-TM) with an E50 of 254 nM. It is used in research on reducing intraocular pressure (IOP).

Glycitin (Glycitein 7-O-β-glucoside), a natural isoflavone isolated from legumes, promotes the proliferation of bone marrow stromal cells and osteoblasts while suppressing bone turnover.

Glucosylgalactosylhydroxylysine is a bone formation and bone resorption marker that is related to bone turnover processes during growth and development as well as metabolic bone diseases.

Ganglioside GQ1b is a tetrasialoganglioside that contains two sialic acid residues linked to an inner galactose unit. It stimulates phosphorylation of several ecto-type protein kinase substrates on the surface of GOTO human neuroblastoma cells when used at a concentration of 5 nM. Ganglioside GQ1b promotes differentiation of murine embryonic stem cells (mESCs) to neuronal precursor and glial cells via activation of the ERK1/2 pathway. It also induces differentiation of murine keratinocytes through phosphoinositide turnover. Ganglioside GQ1b mixture contains ganglioside GQ1b molecular species with C18:1 and C20:1 sphingoid backbones.

Osteocalcin (1-49) is a non-collagenous peptide that is secreted by osteoblasts and odontoblasts and comprises 1-2% of the total protein in bone. Secretion of osteocalcin (1-49) is stimulated by 1,25-dihydroxy vitamin D and plasma levels increase in diseases that induce dysregulated bone turnover such as osteoporosis, Paget's disease, and primary hyperparathyroidism. Osteocalcin (1-49) is positively correlated with insulin sensitivity and negatively correlated with high blood glucose levels in women. In vitro, osteocalcin induces chemotaxis of MDA-MB-231 breast cancer cells, human peripheral blood monocytes, and rat osteosarcoma cells with osteoblast-like characteristics. It is also expressed by vascular smooth muscle cells (VSMCs) displaying an osteoblast-like phenotype and has been positively associated with calcification of aortic tissue and heart valves in humans.

Inactivation of the tumor suppressor p53 commonly coincides with increased signaling through NF-κB in cancer. CAY10681 is a dual modulator of p53-MDM2 interaction and NF-κB signaling. It potently binds MDM2 (Ki = 250 nM), reducing MDM2-mediated turnover of p53. CAY10681 also inhibits phosphorylation of IκBα and dose-dependently reduces nuclear accumulation of p65. It blocks the proliferation of cancer cell lines (IC50s range from 33 to 37 μM). CAY10681 exhibits excellent oral bioavailability and inhibits tumor growth in A549 xenografts in nude mice.