slow-binding

LDN-27219 is a potent hTGase inhibitor with IC50 of 0.6 uM.

AACOCF3 (Arachidonyl trifluoromethyl ketone) is a cell-permeable trifluoromethyl ketone analog of arachidonic acid and a potent, selective slow binding inhibitor of the 85-kDa cytosolic phospholipase A2 (cPLA2). By blocking the production of arachidonate and 12-hydroxyeicosatetraenoic acid in calcium ionophore-challenged platelets, AACOCF3 hinders their synthesis. Additionally, AACOCF3 inhibits glucose-induced insulin secretion from isolated rat islets, making it promising for cardiovascular disease research.

EMD57033 is a cardiac troponin C (cTnC) activator, a dominant Ca2+ sensitizer, which functions by binding to cardiac slow skeletal troponin C heterodimers to promote cardiac contraction.

SID 26681509 is a selective, reversible and competitive human cathepsin L inhibitor (IC50 of 56 nM).

FK706 is a slow-binding and competitive human neutrophil elastase inhibitor (IC50: 83 nM; Ki: 4.2 nM). FK706 also inhibits mouse neutrophil elastase and porcine pancreatic elastase (IC50s: 22 nM and 100 nM, respectively). FK706 has an anti-inflammatory ef

DSPE-PEG(2000)-biotin is a biotinylated and PEGylated form of 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine. This compound is extensively used in both in vitro and in vivo for the delivery of small molecule liposomes, as well as for fluorescently labeling nanoparticle lipid carriers (NLCs). Additionally, DSPE-PEG(2000)-biotin is employed to form micelles and serves as a precursor for immobilizing liposomes, utilized in biolayer interferometry binding experiments. Liposomes containing DSPE-PEG(2000)-biotin, encapsulating doxorubicin and quercetin, exhibit cytotoxicity against MCF-7 adr multidrug-resistant breast cancer cells in vitro and slow tumor growth in the MCF-7 adr mouse xenograft model. Fluorescent labeling of NLCs containing DSPE-PEG(2000)-biotin has been successfully achieved using avidin conjugated with FITC-labeled biotin.

L 708286 is an agent of peptide-based phenethylcarbamoyldifluoromethylene. It is a slow-binding inhibitor of human leucocyte elastase (HLE).

ONO-0300302 is a slow tight binding LPA1 antagonist (IC50: 0.16 nM) used to treat Benign Prostatic Hyperplasia. ONO-0300302 inhibits significantly an LPA-induced increase of intraurethral pressure (IUP) in rat (3 mg kg, p.o.) and dog (1 mg kg, p.o.) over

SL-25.1188 is a monoamine oxidase B (MAO-B) inhibitor. SL-25.1188 is characterized by reversible binding, high brain uptake, and very slow plasma metabolism in vivo.

UR-2922 is an oral antagonist of platelet GPIIb/IIIa. UR-2922 possessed a high affinity for the human platelet receptor (K(d) <1 nM) and a slow dissociation rate (k(off)= 90 min) in vitro. UR-2922 induced no ligand-induced binding sites (LIBS) expression

Pimelic diphenylamide 106 (RGFA-8) is a slow, tight-binding inhibitor of class I HDAC (with IC50 values of 150 nM , 760 nM and 370 nM for HDAC 1, 2, and 3, respectively), showing no activity against class II HDACs.

11-trans Leukotriene C4 (11-trans LTC4) is a C-11 double bond isomer of LTC4. LTC4 undergoes slow temperature-dependent isomerization to 11-trans LTC4 during storage. 11-trans LTC4 is produced in smaller amounts relative to LTC4 in ionophore-stimulated HMC-1 cells (a human mast cell line) and equine eosinophils, but not in human neutrophils or RBL-1 cells. It is nearly equipotent with LTC4 for contraction of guinea pig parenchymal and ileum. In a radioligand binding assay using guinea pig ileum as a cysteinyl leukotriene receptor preparation, the pKis for LTC4 and 11-trans LTC4 were determined to be 6.42 and 6.58, respectively.

Ara-F-NAD+, an arabino analogue of NAD + , is a potent, slow-binding CD38 NADase inhibitor, with a K i of 169 nM.

UCB-5307 is a small molecule compound that inhibits TNFR1 signal transduction and downstream function in vitro. The KD of human TNFα is 9 nM. The TNF was directly bound by slow binding kinetics,KD= 6 nM. UCB-5307 can pass through prefabricated hTNF hTNFR1 complexes.

Tiotropium Bromide hydrate (BA-679 BR hydrate) is a potent anticholinergic and bronchodilator, serving as a muscarinic receptor antagonist, specifically targeting mAChR. It is developed for treating chronic obstructive airways disease (COPD), demonstrating novel and long-lasting effects. Binding studies with [3H]tiotropium bromide in human lung reveal its high potency and equivalent affinity for M1-, M2-, and M3-receptors, making it roughly 10 times more effective than ipratropium bromide. It notably inhibits cholinergic nerve-induced contraction of both guinea-pig and human airways more potently than atropine or ipratropium bromide, albeit with a slower onset. Tiotropium bromide uniquely presents slow dissociation from M3-receptors on airway smooth muscle and rapid dissociation from M2 autoreceptors on cholinergic nerve terminals. As a quaternary ammonium derivative, it shows high affinity and special kinetic selectivity towards muscarinic receptors across M1-, M2-, and M3-subtypes, due to its slower dissociation from M1- and M3-receptors compared to M2-receptors.

RO-5328673 is a dual NK2 NK3 antagonist. O5328673. [(3)H]RO5328673 bound to a single saturable site on hNK2, hNK3 and gpNK3 with high-affinity. RO5328673 acted as an insurmountable antagonist at both human and guinea-pig NK3 receptors in the [(3)H]IP accumulation assay. In binding kinetic analyses, [(3)H]RO5328673 had fast association and dissociation rates at hNK2 while it had a fast association rate and a remarkably slow dissociation rate at gp and hNK3. In electrophysiological recordings of gp SNpc, RO5328673 inhibited the senktide-induced potentiation of spontaneous activity of dopaminergic neurons with an insurmountable mechanism of action. RO5328673 exhibited in-vivo activity in gerbils, robustly reversing the senktide-induced locomotor activity.

Oxocarbazate, also known as CID23631927, is an inhibitor of human cathepsin L. In the cathepsin L inhibition assay, The oxocarbazate caused a time-dependent 17-fold drop in IC50 from 6.9 nM (no preincubation) to 0.4 nM (4-h preincubation). Slowly reversible inhibition was demonstrated in a dilution assay. CID23631927 demonstrate activity in blocking both SARS-CoV (IC50 = 273 nM) and Ebola virus (IC50 = 193 nM) entry into human embryonic. CID 23631927 was a subnanomolar, slow-binding, reversible inhibitor of human cathepsin L that blocked SARS-CoV and Ebola pseudotype virus entry in human cells. Inhibition of cathepsin L thus holds promise for therapeutic intervention for both SARS-CoV and Ebola virus infection.

Ara-F-NAD+ sodium, an arabino analogue of NAD+, serves as a potent, reversible, and slow-binding inhibitor of the CD38 NADase [1] [2].

1400W is a slow, tight-binding, and highly selective inducible nitric-oxide synthase (iNOS) inhibitor, with a K_d value ≤ 7 nM. 1400W inhibits iNOS induction in microglial cells and reduces the generation of NO, thereby mitigating oxidative stress and neuronal cell apoptosis in the rat cerebral cortex, and improving spatial memory dysfunction caused by acute hypobaric hypoxia-reoxygenation [1] [2].

HDAC6-IN-33 (compound 6), an irreversible and selective HDAC6 inhibitor, demonstrates a potency with an IC 50 of 193 nM and lacks activity against HDAC1-4. This compound adheres to HDAC6 through a two-step slow-binding mechanism, establishing it as a tight-binding inhibitor [1].

ITF5924 (compound 1), a potent HDAC6 inhibitor featuring a difluoromethyl-1,3,4-oxadiazole (DFMO) moiety, exhibits an IC 50 of 7.7 nM and surpasses 104-fold selectivity over other HDAC subtypes. As a slow-binding substrate analog of HDAC6, ITF5924 undergoes an enzyme-catalyzed ring opening reaction, resulting in the formation of a stable, long-lasting enzyme-inhibitor complex [1].

MAO-A B-IN-3 (Compound 12) demonstrated moderate permeability in in vitro experiments, with rates recorded at 16.49 nm s in Caco2 cells and 103.16 nm s in MDCK cells. The compound exhibited a high plasma protein binding rate of 90.97%, indicative of strong binding, suggesting it has an extended half-life and slow excretion characteristics.

Broussonin C and broussin are antifungal compounds. Broussonin C exerts simple reversible slow-binding inhibition against diphenolase.