state-dependent

Ordopidine (ACR325) is a dopaminergic stabilizer that suppresses psychostimulant-induced hyperactivity disorder and stimulates behavior during inactivity. Ordopidine acts as a dopamine D2 receptor antagonist in vitro and, despite its low affinity, its specific state-dependent behavioral effect characteristics are not generally shared by D2 receptor antagonists.

CBR-5884 is an selective, active of phosphoglycerate dehydrogenase (PHGDH) inhibitor with an IC50 of 33 μM. CBR-5884 inhibits de novo serine synthesis in cancer cells and is selectively toxic to cancer cell lines with high serine biosynthetic activity. CBR-5884 selectively inhibits the proliferation of melanoma and breast cancer lines that have a high propensity for serine synthesis. Biochemical characterization of the inhibitor revealed that it was a noncompetitive inhibitor that showed a time-dependent onset of inhibition and disrupted the oligomerization state of PHGDH

Raxatrigine hydrochloride is a state-dependent sodium channel blocker and a Nav1.7 sodium channel inhibitor.

Ro 44-3888, the active component of sibrafiban, achieves predictable plasma concentrations when administered orally in its prodrug form, Ro 48-3657. Upon reaching a steady state after the second dose, Ro 44-3888 exhibits concentration-dependent inhibition of platelet aggregation and prolongs bleeding time. These findings suggest that Ro 44-3888 merits further evaluation, especially in patients at high risk of arterial thrombosis and those with acute coronary syndrome, due to its reliable absorption.

Co 102862 is a voltage-gated sodium channel blocker. Co 102862 can be used for anticonvulsant studies.

AFD-21 is a class I antiarrhythmic drug. It binds to sodium channels in their inactivated state and exerts use- and voltage-dependent inhibition of sodium channels with unbinding rates comparable to those of class I antiarrhythmic drugs with moderate kinetics.

TROX-1 is the activation state-dependent Cav2 channel antagonist.

Resolvins are a family of potent lipid mediators derived from both eicosapentaenoic acid and docosahexaenoic acid.[1] In addition to being anti-inflammatory, resolvins promote the resolution of the inflammatory response back to a non-inflamed state.[2] Resolvin D1 is produced physiologically from the sequential oxygenation of DHA by 15- and 5-lipoxygenase.[1] 17(R)-RvD1 is an aspirin-triggered epimer of RvD1 that reduces human polymorphonuclear leukocyte (PMN) transendothelial migration, the earliest event in acute inflammation, with equipotency to RvD1 (EC50 = ~30 nM).[3] 17(R)-RvD1 exhibits a dose-dependent reduction in leukocyte infiltration in a mouse model of peritonitis with maximal inhibition of ~35% at a 100 ng dose.[3] In contrast to RvD1, the aspirin-triggered form resists rapid inactivation by eicosanoid oxidoreductases. Analytical and biological comparisons of synthetic 17(R)-RvD1 with endogenously derived 17(R)-RvD1 have confirmed its identity as matching the natural product.[4]

RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 μM), showing no effect on PAR-2, PAR-3, or PAR-4. It inhibits the aggregation of human platelets induced by SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), with high selectivity relative to U46619. RWJ-56110 dihydrochloride also blocks angiogenesis and the formation of new vessels in vivo, and induces cell apoptosis[1][2].

APS-2-79, a KSR-dependent MEK antagonist, disrupts ATP (biotin) binding within the KSR2-MEK1 complex, achieving an inhibitory concentration (IC50) of 120 nM. This action stabilizes the KSR inactive state and antagonizes oncogenic Ras-MAPK signaling.

CNV-2197944 is a novel, small molecule, state-dependent calcium channel blocker, designed to selectively inhibit highly active Cav2.2 channels.

Nav1.3 Channel Inhibitor 1 (Compound 15b) is a state-dependent inhibitor of the voltage-gated sodium channel Na v 1.3, with an IC50 value of 20 nM. It has the ability to cross the blood-brain barrier, making it applicable for research into nervous system disorders [1].

PF-05186462 (PF-05150122) is a potent, state-dependent, subtype selective Nav1.7 inhibitor with IC50 of 21 nM, no significant activity against Nav1.5.

OX-201 is a selective agonist for OX2R with an EC50 of 8 nM. Pathological proteins produced by neurons are released into the interstitial fluid (ISF) in a neural activity-dependent manner and subsequently cleared from the brain via lymphatic pathways. The efflux of these proteins to the ISF correlates with the wakeful state of neurons. OX-201 can induce neuronal awakening and enhance the release of tau into the hippocampal ISF. While it does not alter hippocampal tau levels, OX-201 has potential applications in Alzheimers disease (AD) related to sleep wake cycle disturbances.

26-Nor-8-oxo-alpha-onocerin can promote the osteoblast proliferation rate, the effect is time-dependent,concentration-dependent and differentiation state-dependent.

Didrovaltrate shows cytotoxic against human cancer cell lines. Didrovaltrate blocks I(Ca-L) in a concentration-dependent manner and probably inhibits I(Ca-L) in its inactive state, which may contribute to its cardiovascular effect.