turnover

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

Gentiobiose is a natural oligosaccharide that promotes fruit ripening.

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

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.

M3258 is an immunoproteasome subunit LMP7 (β5i) inhibitor, with an IC50 of 3.6 nM for LMP7 and 3.4 nM at the cellular level. In a multiple myeloma xenograft model, M3258 exhibits significant antitumor activity. In multiple myeloma cells, M3258 significantly and persistently inhibits LMP7 activity and ubiquitinated protein turnover in tumor tissues, further inducing apoptosis.

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.

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.

L-Eflornithine monohydrochloride is an irreversible ornithine decarboxylase (ODC) inhibitor with a KD of 1.3±0.3 μM, and a Kinact of 0.15±0.03 min-1. L-Eflornithine monohydrochloride (L-DFMO monohydrochloride) is an enantiomer of Eflornithine. L-Eflornithine is utilized in enzymology and polyamine biosynthesis research systems to investigate irreversible inhibition kinetics of ornithine decarboxylase, including enzyme inactivation parameters (KD and Kinact) and their relationship to catalytic turnover regulation in cellular metabolic models. L-Eflornithine monohydrochloride (L-DFMO monohydrochloride) is further applied in stereochemical and structure–activity relationship studies evaluating enantiomer-dependent enzyme binding and inhibition efficiency in biochemical assay systems.

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.

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 is the indole form of Indapamide that serves as a quantitative analytical standard for measuring Indapamide turnover by CYP3A4, demonstrating approximately tenfold higher metabolic turnover than Indoline and slightly enhanced CYP3A4 affinity, thereby supporting detailed studies of drug metabolism, enzyme kinetics, and pharmacokinetic profiling.

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).

ST80 is an inhibitor of the interaction between OTUD4 and CD73. It decreases CD73 protein levels, enhances the turnover rate of CD73, and reduces immune evasion by tumor cells, thereby exhibiting antitumor effects against immune-suppressive triple-negative breast cancer (TNBC).

EBP-IN-1 (compound 11) is an inhibitor of emopamil binding protein (EBP), which is a sterol isomerase in the cholesterol biosynthesis pathway. This compound exhibits a long half-life in rodents and demonstrates favorable metabolic turnover and brain penetration properties. EBP-IN-1 promotes the formation of oligodendrocytes in human cortical organoids.

LCZ960 is an orally active glucokinase (GK) activator that stimulates GK activity in liver cells in vitro and enhances glucose uptake in vivo by activating hepatic GK. It effectively lowers blood glucose levels in diet-induced obesity (DIO) in mice. LCZ960 maintains normal blood sugar and improves glucose tolerance in DIO mice and rats. Additionally, LCZ960 stimulates glycogen synthase flux and increases glycogen turnover in the liver of rats, inducing an increase in hepatic glycogen cycling. This compound is useful for research on obesity and type 2 diabetes induced by high-fat diets.

(+)-AJ-76 is an antagonist of the dopamine autoreceptor, with a weak antagonistic effect on postsynaptic dopamine receptors. (+)-AJ 76 HCl can increase the synthesis and turnover of dopamine in the rat brain, and can also antagonize the sedative effect of low-dose apomorphine.