The team used a library of about 100 such compounds, all known to inhibit enzymes called serine hydrolases
Cravatt, "Activity-based proteomics of enzyme superfamilies: serine hydrolases
as a case study," Journal of Biological Chemistry, vol.
When used in a complex proteome, ABPs report on the active site occupancy of all members of an enzyme family, thus making them ideal tools to simultaneously screen dozens of targets against potential inhibitors.The goal of this proposal is to run a pilot study by screening 400 of the most promising antimalarial compounds against all serine hydrolases
, cysteine proteases, and ATPases found in infected red blood cells.
ABX-1431, which was discovered with Abide's proprietary technology platform targeting serine hydrolases
, has completed dosing in a first-in-human study assessing the safety, tolerability, pharmacodynamics, and pharmacokinetics of the molecule in single-ascending and multiple-ascending doses in healthy volunteers.
Acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE) comprise a family of enzymes which include serine hydrolases
. The different specificities for substrates and inhibitors for these enzymes are due to the differences in amino acid residues of the active sites of AChE and BChE.
The product was discovered using the company's proprietary technology platform, which finds new small molecule drug candidates that target serine hydrolases
, a large class of enzymes with important regulatory roles in human physiology and disease.
AND DEREWENDA, U., 1991.Relationships among serine hydrolases
: evidence for a common structural motif in triacylglyceride lipases and esterases.
funiculosum have pH optima at 5.5 or 6.0, respectively, and (v) most of them are inhibited by serine hydrolase
inhibitors such as diisopropylfluorophosphate or acylsulfonyl compounds, which bind covalently to the active site of serine hydrolases
The researchers have used a set of compounds, recently synthesized by Cravatt's laboratory, that tend to inhibit serine hydrolases
Metabolism of profenofos enantiomers yields a mixture of toxicants that includes direct-acting and cytochrome P450 (CYP450)-activated inhibitors of acetylcholinesterase (AChE) and other serine hydrolases
(Glickman et al.
The contract centres around Abide's technologies to selectively aim serine hydrolases
, "one of the largest enzyme families involved in regulating human physiology." These enzymes play a key role in areas such as "regulating CNS signalling, digestion, metabolism, inflammation, blood clotting, and life cycle of viruses and pathogens".
In a new study the researchers show the new compounds powerfully and selectively block the activity of a large and diverse group of enzymes known as "serine hydrolases