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.

QLS-81 is a Nav1.7 channel inhibitor (IC50: 1.5 μM) with significant analgesic properties, effective in alleviating neuropathic and inflammatory pain. It exerts frequency-dependent inhibition by targeting the inactivated state of Nav1.7 channels. QLS-81 is applicable in chronic pain research.

GPV0057 (Compound 5d) is a potent and selective inhibitor of P-glycoprotein (P-gp). It also acts as a selective activator of the potassium channel Kir2.1. By competitively binding at the substrate binding site of P-gp, GPV0057 inhibits ATP-dependent drug efflux, thereby reversing multidrug resistance in tumor cells. Additionally, it stabilizes the open state of Kir2.1, enhancing potassium ion influx. GPV0057 has potential applications in the study of tumors with high P-gp expression and Kir2.1-related diseases, such as heart failure and Andersen-Tawil syndrome.

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.