ATPases are enzymes that convert ATP to ADP through the hydrolysis of a phosphate bond. There are four different types of ATPases (P, V, F, and ABC types) that operate within biological membranes to ensure moving many different types of ions or molecules across these membranes (Fig. 1.) [1]. The energy released during this process is utilized for the catalysis of other cellular reactions. Thus, ATPases are crucial enzymes engaged in energy homeostasis and signal transduction [2]. Also, mutations in these proteins account for numerous diseases from cancer to those that affect bones (osteoporosis), ears (hearing), eyes (macromolecular degeneration), the heart (hypercholesterolemia/cardiac arrest), immune system (immune deficiency disease), kidney (nephrotoxicity), lungs (cystic fibrosis), pancreas (diabetes and cystic fibrosis), skin (Darier disease), and stomach (ulcers) [1, 3].
Life Chemicals has designed its proprietary ATPase Focused Screening Library of over 13,500 drug-like screening compounds with a 2D fingerprint similarity search against two different reference databases using the MDL public keys (75-85 % Tanimoto similarity cut-off).
The compound selection can be customized based on your requirements, cherry picking is available.
Please, contact us at orders@lifechemicals.com for any additional information and price quotations.
For a pre-plated set based on this Screening Library, please explore our Pre-plated Focused Libraries.
Figure 1. Classification of ATPase and its inhibitors [4]
Compound selection
First, the Life Chemicals HTS Compound Collection was screened against 30,000 reference compounds with reported activity values lower than 11 uM by similarity search (85 % Tanimoto similarity cut-off) to provide a set of over 5,000 structurally-diverse screening compounds with potential ATPase inhibitory activity against different target types.
The following ATPases were selected as drug targets:
- 26S proteasome non-ATPase regulatory subunit 14
- ATPase family AAA domain-containing protein type 2 and 5
- Cystic fibrosis transmembrane conductance regulator ATPase Activity
- Katanin p60 ATPase-containing subunit A1
- Multidrug resistance-associated protein 1 ATPase Activity
- Potassium-transporting ATPase
- Sodium/potassium-transporting ATPase
- Transitional endoplasmic reticulum ATPase
- V-type proton ATPase subunit c'
Then the HTS Compound Collection was filtered against a reference set of 13,000 biologically active compounds from 127 ATPase-related assays, using the data available from patents, scientific publications and other sources (according to the PubChem and ChEMBL databases). As a result, around 8,500 potential ATPase inhibitors were additionally selected using the 75 % Tanimoto similarity. All results could be traced back to the targets or assays indicated in the column “Target type” or “Description” within the corresponding SD file.
The list of selected targets from this reference set is represented below:
- p97 ATPase
- SV40 T antigen (inhibit the ATPase activity of Tag - tumor antigen)
- Hsp70 protein (GST-tagged ATPase domain)
- ATPase - based assay for small molecule DnaK Modulators targeting the beta-domain
- Inhibitors of Dynein Mediated Cargo Transport on Microtubules
- Sic1-GFP Fusion Protein
- CS receptor on Na+-ATPase
- Inhibition of V-ATPase activity in African green monkey COS7 cells
- Inhibition of Escherichia coli RecA by ADP-linked fluorescent ATPase assay
- RecA ATPase inhibitors
- Saccharomyces cerevisiae V-ATPase subunit B
- Na+/K+ ATPase (including inhibition of rat kidney Na+/K+ ATPase)
- Inhibition or activation of verapamil-stimulated ATPase activity of P-glycoprotein
- Inhibition of Escherichia coli 60 kD a chaperonin groEL I493C mutant ATPase activity
- SecA ATPase
- B2 subunit of vacuolar H+-ATPase (V-ATPase)
- Pgp-ATPase activity
- ATPase activity of Eg5
- H+/K+ ATPase from pig gastric mucosa
- cardiac SR-CA2+-pumping ATPase
- Kinesin spindle protein (KSP)
- Hsp90 ATPase activity
- MRP1 ATPase activity
- DNA gyrase B ATPase activity
- VCP(valosin-containing protein)
- V-type proton ATPase subunit B
- ABCB
Reference:
- Ishmukhametov R. ATPase: Overview. In: Roberts G.C.K. (eds) Encyclopedia of Biophysics. Springer, Berlin, 2013, Heidelberg. 10.1007/978-3-642-16712-6_207.
- Iyer LM, Leipe DD, Koonin EV, Aravind L. Evolutionary history and higher order classification of AAA+ ATPases. J Struct Biol. 2004;146(1-2):11-31. 10.1016/j.jsb.2003.10.010.
- Ghosh S., Sen P.C. Role of ATPases in Disease Processes. In: Chakraborti S., Dhalla N. (eds) Regulation of Ca2+-ATPases,V-ATPases and F-ATPases. Advances in Biochemistry in Health and Disease. 2016;14. Springer, Cham. 10.1007/978-3-319-24780-9_24.
- https://www.selleck.co.jp/ATPase.html