Metabolism

4-epiMinocycline, recognized as a primary degradation product and a probable impurity in minocycline commercial formulations, is derived from minocycline, a broad-spectrum tetracycline antibiotic notable for its extended serum half-life. Besides treating acne, especially in older patients, minocylvania exhibits significant anti-inflammatory and neuroprotective effects.

Cyclophellitol aziridine, an analogue of cyclophenol, serves as a potent inhibitor of β-glucosidase [1].

A 79175 is a 5-lipoxygenase inhibitor that increases bone formation.

Gisadenafil (UK-369003) is a selective inhibitor of phosphodiesterase 5 (PDE5) with an IC50 of 3.6 nM and prevents degradation of cGMP.

Miglustat hydrochloride (N-Butyldeoxynojirimycin hydrochloride) is an inhibitor of glucosylceramide synthase and can be used for studies about Type I Gaucher

PDE5-IN-2 is a potent, highly selective, and orally active inhibitor of PDE5(IC50 of 0.31 nM)

Niraxostat (Y-700) is one of the isocytosine derivatives as xanthine oxidase inhibitors.

1,2-Dipalmitoyl-3-myristoyl-rac-glycerol, a triacylglycerol, incorporates palmitic acid at the sn-1 and sn-2 positions, along with myristic acid at the sn-3 position, and is identified in bovine milk fat.

1-Palmitoyl-2-Linoleoyl-sn-glycero-3-phosphatidylcholine (PC) is a phospholipid characterized by the incorporation of palmitic (16:0) and linoleic (18:2) acids at the sn-1 and sn-2 positions, respectively. It is utilized in the creation of micelles, liposomes, and various artificial membranes, playing a significant role in research on lipid peroxidation.

"Casein kinase 1δ-IN-4 (compound 567) is a potent inhibitor of casein kinase 1δ with potential application in Alzheimer's disease research [1]."

TMP780 is an inverse RORγt agonist (IC50: 13 nM). RORγt is a tractable drug target for the treatment of cutaneous inflammatory disorders.

ICMT-IN-33 (compound 73) functions as an ICMT inhibitor with an IC50 value of 0.46 μM [1].

GNE-618 is a potent and orally active inhibitor of nicotinamide phosphoribosyltransferase (IC50: 6 nM).

EMD638683 is a highly selective SGK1 inhibitor with IC50 of 3 μM. EMD638683 R-Form is the R-form of EMD638683.

Adibendan (Adibendanum) is a selective inhibitor of PDE3 with an IC50 of 2.0 μM.

Fatty acid amide hydrolase (FAAH), an enzyme responsible for the hydrolysis and inactivation of fatty acid amides like anandamide and oleamide, has been identified as a target by the potent FAAH inhibitor PHOP. PHOP demonstrates remarkable inhibitory activity with K_i values as low as 0.094 nM for human FAAH and 0.2 nM for rat FAAH. Additionally, through a proteomics assay focusing on the serine hydrolase enzyme family, to which FAAH belongs, PHOP's selectivity was evaluated, presenting IC_50 values of 1.1 nM against FAAH, 1.4 nM against triacylglycerol hydrolase (TGH), and greater than 100 µM against an uncharacterized hydrolase (KIAA1363). This specificity profile of PHOP underscores its potential for yielding precise outcomes in studies involving complex biological systems.

17(R)-Resolvin D3 (17(R)-RvD3) is an aspirin-triggered epimer of resolvin D3, produced from docosahexaenoic acid (DHA) through the action of COX-2 in the presence of aspirin, via a 17(R)-hydroperoxy DHA (17(R)-HDHA) intermediary. Identified in mouse inflammatory exudates, 17(R)-RvD3 notably inhibits the transmigration of isolated human polymorphonuclear cells (PMNs) and fosters the efferocytosis of apoptotic PMNs by macrophages. Furthermore, in a mouse model of zymosan-induced peritonitis, 17(R)-RvD3 administration (10 ng/animal) significantly curtails neutrophil infiltration into the peritoneal cavity and modulates cytokine levels by reducing IL-6 and increasing IL-10 in the inflammatory exudate. It engages GPR32, evidenced by activation in a β-arrestin reporter assay and augments phagocytosis more effectively in CHO cells overexpressing GPR32 compared to controls. Additionally, 17(R)-RvD3 enhances the clearance of etoposide-induced tumor cell debris by monocyte-derived macrophages in H460 human lung carcinoma.

Sampatrilat, an oral vasopeptidase inhibitor, more potently blocks C-domain ACE (Ki=13.8 nM) over N-domain (Ki=171.9 nM).