Metabolism

GGTI-2133: potent GGTase I inhibitor, IC50=38 nM; blocks inflammatory cell invasion in mice asthma.

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.

MAGL-IN-6, a powerful MAGL blocker, IC50 at 4.71 nM, may assist in neurological disease research.

ICMT-IN-19 (compound 53) serves as a potent inhibitor of ICMT, demonstrating an IC50 value of 0.026 μM [1].

3-Hydroxycarbofuran, a principal metabolite of Carbofuran, acts as a reversible inhibitor of acetylcholinesterase (AChE) [1].

QH536 degrades HMGCR (EC50: 0.22 μM), has anti-inflammatory properties, and avoids cholesterol buildup; useful for cardiovascular and NASH research.

LMPTP INHIBITOR 1 hydrochloride is a selective inhibitor of low molecular weight protein tyrosine phosphatase ( LMPTP ), with an IC 50 of 0.8 μM for LMPTP-A.

Fasidotril inhibits NEP/ACE, treats high blood pressure in rats, effective in humans with hypertension.

ZK824859 is an oral uPA inhibitor with IC50s: 79 nM (uPA), 1580 nM (tPA), 1330 nM (plasmin).

FR-190809 is a nonadrenotoxic and orally efficacious inhibitor of acyl-CoA:cholesterol O-acyltransferase (ACAT) (IC50: 45 nM).

Ilepatril, also known as AVE-7688, is a vasopeptidase inhibitor for the treatment of hypertension.

hCAIX-IN-15 is a potent inhibitor of human carbonic anhydrase IX (hCA IX) with an inhibition constant (Ki) of 38.8 nM, exhibiting broad-spectrum anticancer

α-Glucosidase-IN-28 (Compound 18) is an α-glucosidase inhibitor with an IC50 of 0.62 μM and Ki value of 3.93 μM.

1-Aminodecylidenebis-phosphonic acid, with its potent inhibitory effect on acid sphingomyelinase (IC50= 20 nM), shows selectivity by being less effective against neutral sphingomyelinase (IC50= >100 μM). Additionally, it entirely prevents dexamethasone-induced apoptosis in HepG2 cells.

Me-Indoxam is an inhibitor of sPLA2. It has no effect on arachidonic acid release and platelet activating factor synthesis.

hCAIX/XII-IN-8 (compound 3g) is a potent inhibitor of the human carbonic anhydrases (CAs) IX and XII, with inhibition constants (K i) of 8.5 nM for CA IX and 6.

CAY10502 inhibits cPLA2α (85 kDa), crucial in inflammation/arachidonic cascade, with 4.3 nM IC50, reducing arachidonic acid in human platelets.

17(R)-Resolvin D1 (17(R)-RvD1) is an aspirin-triggered epimer of RvD1 that equivalently inhibits human polymorphonuclear leukocyte migration across the endothelium (EC50= ~30 nM), a precursor to acute inflammation. Unlike RvD1, it resists rapid degradation by eicosanoid oxidoreductases. In a mouse peritonitis model, 17(R)-RvD1 dose-dependently reduces leukocyte infiltration, achieving up to a 35% decrease with a 100 ng dose. Additionally, its methyl ester derivative, designed to enhance its pharmacokinetic and distribution properties as a more lipophilic prodrug, can be converted back into the active acid form by intracellular esterases.

9-OxoODE, formed through the oxidation of the allylic hydroxyl group in both 9(S)-HODE and 9(R)-HODE, is present in rabbit reticulocyte plasma and mitochondrial membranes as both 9- and 13-oxoODEs, constituting approximately 2% of the total linoleate residues. The majority of these oxidized linoleate residues are esterified to membrane lipids.

γ-CEHC, a metabolite of γ-tocopherol, is predominantly excreted through urine, primarily in its conjugated form as glucuronide [1], rather than through bile.