Carboxylesterase (CES)

Tefinostat (CHR-2845) is a monocyte/macrophage-targeted pan HDAC inhibitor, cleaved into active acid CHR-2847 by the intracellular esterase human carboxylesterase-1 (hCE-1). Anti-monocytoid lineage leukaemias activity.

Nevadensin is a selective inhibitor of human carboxylesterase 1 (hCE1), exhibiting an IC50 value of 2.64 μM, while demonstrating significantly lower selectivity for hCE2 (IC50 of 132.8 μM). This natural flavonoid has been shown to induce apoptosis and DNA damage in cancer cells, indicating its potential for therapeutic applications in oncology. Additionally, Nevadensin displays a range of bioactivities, including anti-inflammatory, anti-tumor, anti-hypertensive, anti-tubercular, antitussive, antioxidant, and anti-microbial effects, making it a valuable agent for various research investigations.

Carboxylesterase-IN-3 is a highly potent inhibitor of Carboxylesterase Notum, exhibiting an IC50 of 10 nM or lower. Notum plays a critical role as a negative regulator of Wnt signaling by hydrolyzing palmitoleoylate esters necessary for Wnt activity. This compound is valuable for research applications focused on cancer biology, particularly in studies investigating the modulation of Wnt signaling pathways.

Carboxylesterase-IN-2 is a highly potent inhibitor of Carboxylesterase Notum, exhibiting an IC50 of 10 nM or lower. Notum functions as a negative regulator of Wnt signaling by hydrolyzing palmitoleoylate esters, which are essential for Wnt activity. This compound is valuable for investigating the role of Notum in cancer biology and the modulation of Wnt signaling pathways.

WZU-13 is a potent inhibitor of carboxylesterase (CES), demonstrating significant inhibition of 77% at a concentration of 100 μM. This compound is valuable for research applications aimed at studying the role of CES in drug metabolism and detoxification processes. WZU-13 can aid in elucidating the enzymatic mechanisms and biological functions of CES in various physiological and pathological contexts.

Dibromsalicil is a selective inhibitor of carboxylesterases (CES), exhibiting inhibitory activity with IC50 values of 72.7 nM against human intestinal carboxylesterase (hiCE) and 53.5 nM against rabbit liver carboxylesterase (rCE). This compound demonstrates minimal activity against human liver carboxylesterase (hCE1) and cholinesterase, making it a valuable tool for research applications focused on drug metabolism and enzymatic activity modulation. Its specificity for hiCE and rCE positions Dibromsalicil as an important reagent for studying carboxylesterase-related pathways.

Isolicoflavonol is a potent inhibitor of hCES2A (Human carboxylesterase 2), exhibiting reversible and mixed inhibition of fluorescein diacetate hydrolysis. With Ki values below 1.0 μM, it serves as a valuable tool for exploring enzymatic activity and regulation in biochemical research. Its specificity and efficacy make it suitable for investigations into drug metabolism and enzyme kinetics.

CES2-IN-1 is a reversible and selective inhibitor of human carboxylesterase 2 (hCES2), exhibiting an IC50 value of 6.72 μM. This compound effectively reduces CES2 levels in living cells, making it useful for studies involving drug metabolism. CES2-IN-1 has demonstrated efficacy in preclinical models for conditions such as irinotecan-induced delayed diarrhea and dextran sulfate sodium (DSS)-induced ulcerative colitis, supporting its application in gastrointestinal research.

Tanshinone IIA anhydride is a potent irreversible inhibitor of human carboxylesterases, demonstrating Ki values of 1.9 nM for human carboxylesterase 1 and 1.4 nM for human intestinal carboxylesterase. This compound is valuable for studying the regulatory mechanisms of esterases in various biological processes. Its application extends to biochemical studies focused on enzyme inhibition and metabolic pathway analysis.

1-Methylisatin is a selective carboxylesterase (CE) inhibitor, exhibiting inhibitory constants of 38.2 μM for human isoform CE (hiCE) and 5.38 μM for human carboxylesterase 1 (hCE1). This compound interacts with human adult hemoglobin through hydrophobic binding and electrostatic interactions. 1-Methylisatin serves as a valuable tool for investigating the regulation of drug metabolism and biochemical pathways in vivo.

Pancreatic lipase/Carboxylesterase 1-IN-1 is a potent inhibitor of pancreatic lipase (PL) and human carboxylesterase 1A (hCES1A), displaying IC50 values of 2.13 µM and 0.055 µM, respectively. This dual inhibition makes it a valuable tool for studying lipid metabolism and the enzymatic pathways related to drug metabolism and detoxification processes. It has potential applications in research focused on obesity, metabolic disorders, and pharmacokinetics.

Gancaonin I is an isoflavone that serves as a moderate inhibitor of human carboxylesterase 2 (hCES2A) with an IC50 of 1.72 μM. It effectively inhibits the hCES2A-mediated hydrolysis of fluorescein diacetate (FD), making it a valuable tool for research applications involving enzyme regulation and drug metabolism studies.

PMPMEase-IN-1 is a selective inhibitor of carboxylesterase (CES) that targets PMPMEase activity, thereby modulating protein methylation processes. This compound demonstrates potential anti-cancer activity by enhancing sensitivity to polyisoprenyl derivatives, with an effective concentration (EC50) observed in inducing degeneration of human neuroblastoma SH-SY5Y cells. By specifically inhibiting PMPMEase, PMPMEase-IN-1 may contribute to the regulation of polyisoprenyl protein metabolism, promoting normal cellular function. Its utility in research could pave the way for therapeutic advancements in treating cancer and degenerative diseases.

CES2A-IN-3 is a potent inhibitor of human carboxylesterase 2A (hCES2A), acting through a serine-targeting covalent mechanism with an IC50 of 0.12 nM. This compound holds significant promise for research applications related to gastrointestinal disorders, including diarrhea and ulcerative colitis, by modulating enzyme activity linked to these conditions. Its high specificity and efficacy make it an essential tool for exploring hCES2A's role in related biological pathways.

Carboxylesterase-IN-4 is a highly potent inhibitor of carboxylesterase, exhibiting an IC50 of 1.58 nM. This compound facilitates research into cholesterolemia by effectively modulating carboxylesterase activity, making it a valuable tool in the study of lipid metabolism and associated disorders.

Carboxylesterase-IN-5 is an irreversible and competitive inhibitor of carboxylesterase with an IC50 of 21.7 nM for porcine liver carboxylesterase. This reagent is suitable for studies investigating the role of carboxylesterases in metabolic processes and is particularly relevant for research pertaining to hypocholesterolemia. Its specificity and potency make it a valuable tool in biochemical and pharmacological investigations.

Carboxylesterase-IN-1 is a potent carboxylesterase inhibitor, demonstrating significant inhibitory activity at a concentration of 50 μg/mL. By interfering with carboxylesterase function, it serves as a valuable tool in the study of enzyme regulation and pesticide effects on biological systems. This compound is suitable for research applications focusing on enzyme inhibition and the molecular mechanisms of pesticide action.

SQ-24798 is a potent inhibitor of carboxylesterase (CES), specifically designed to bind the zinc ion in the enzyme's active site via its sulfhydryl group, leading to effective enzyme inhibition. This compound exhibits high affinity and specificity, making it a valuable tool in biochemical research focused on understanding CES-related pathways. Its applications include studying drug metabolism and the physiological roles of CES in various biological processes.

Heptenophos is a potent inhibitor of acetylcholinesterase (AChE) and plasma carboxylesterase (CES). By obstructing AChE activity, Heptenophos leads to the accumulation of acetylcholine at cholinergic synapses, which can result in symptoms characteristic of organophosphate poisoning. Its rapid toxicity in animal models, such as male albino mice, allows for the investigation of detoxification strategies, particularly in conjunction with agents like obidoxime and Memantine. This compound is widely utilized in research exploring the mechanisms underlying organophosphate effects and potential antidotal treatments.

2-Thenoyltrifluoroacetone is a chelating agent that targets the mitochondrial electron transport chain, exhibiting an IC50 value of 51.5 μM. It effectively chelates various metal ions and demonstrates cytotoxicity along with anti-tumor activity. This compound holds potential for applications in the treatment of diseases linked to mitochondrial dysfunction, contributing valuable insights into related therapeutic strategies.

Iso-OMPA (Tetraisopropyl pyrophosphoramide) is a selective inhibitor of butyrylcholinesterase (BuChE), functioning through irreversible inhibition. This compound is primarily utilized in research to investigate the mechanisms of BuChE and the resulting effects on acetylcholine metabolism. Iso-OMPA has been shown to enhance soman toxicity in rat models, linked to the inhibition of plasma carboxylesterase (CarbE), making it a valuable tool in studies of nerve agent effects and cholinergic signaling.