non-catalytic

EN523 targets non-catalytic allosteric cysteine C23 in K48 ubiquitin-specific deuquitinase OTUB1.

FT671 is a non-covalent and selective inhibitor of USP7 (IC50: 52 nM) It also binds to the USP7 catalytic domain (Kd: 65 nM).

Aclacinomycin A hydrochloride (Aclarubicin HCl) is an anthracycline antibiotic and inhibitor of topoisomerase I II, interfering with DNA transcription and replication, inhibiting tumour invasion and angiogenesis, generating reactive oxygen species (ROS), and inhibiting the catalytic centre of the 20S proteasome. It is indicated for the treatment of relapsed leukaemia and advanced malignant lymphoma.

hDDAH-1-IN-1 is a selective non-amino acid catalytic site inhibitor of human dimethylarginine dimethylaminohydrolase-1 (hDDAH-1) (Ki: 18 μM).

hDDAH-1-IN-1 TFA is a selective non-amino acid catalytic site inhibitor of human dimethylarginine dimethylaminohydrolase-1 (hDDAH-1) (Ki: 18 μM).

iRucaparib-AP6, a non-trapping PARP1 degrader, blocks both the catalytic activity and scaffolding effects of PARP1. iRucaparib-AP6 is a highly efficient and specific PARP1 degrader based on Rucaparib by using the PROTAC approach.

NKY80 regulates the adenylyl cyclase catalytic activity in heart and lung tissues. NKY80 is a non-competitive inhibitor of adenylyl cyclase type V isoform (IC50s: 8.3 µM, 132 µM, and 1.7 mM for type V, III and II, respectively).

4-Chloropyridine acts as an inhibitor of Nicotinamide N-methyltransferase (NNMT). Serving as a substrate for NNMT, this compound enhances the electrophilicity at the C4 position through methylation of the pyridine nitrogen. This modification facilitates an aromatic nucleophilic substitution reaction with the non-catalytic cysteine (C159) in NNMT, ultimately leading to suicidal activity inhibition of the enzyme. 4-Chloropyridine is a promising candidate for the development of activity-based probes targeting NNMT functions.

KK181N1 is an effective inhibitor of the karrikin (KAR) receptor KAI2. It binds non-covalently to the catalytic pocket of KAI2 and selectively inhibits KAR-induced phenotypes in Arabidopsis.

DPM-1003 is an allosteric inhibitor of PTP1B, targeting the non-catalytic, disordered C-terminal segment of the PTP1B protein, and has shown beneficial effects in reducing pulmonary inflammation in mice.

Bisnorcymserine is a reversible inhibitor of butyrylcholinesterase. The leaving group, bisnoreseroline, interacts in a non-covalent way with Ser(200) and His(440), disrupting the existing interactions within the catalytic triad, and it stacks with Trp(84)

L-Tetraguluronic acid is a straight-chain polysaccharide copolymer consisting of four repeating units involved in the formation of the alginate.L-Tetraguluronic acid interacts with Glu543 in the non-catalytic domain and can help AlyRm1 to bind the substrate more efficiently and to improve the catalytic efficiency.

GNE-6640 is a non-covalent inhibitor targeting ubiquitin specific peptidase 7 (USP7), exhibiting IC50 values of 0.75 μM for full-length USP7, 0.43 μM for the USP7 catalytic domain, 20.3 μM for full-length USP43, and 0.23 μM for Ub-MDM2, respectively.

THR-18 is an 18-mer peptide derived from the sequence of human plasminogen activator inhibitor 1 (PAI-1), having the ability to bind to a site of tissue plasminogen activator (tPA) distal to its catalytic site and uncouple the beneficial clot-dissolving properties of tPA from its deleterious non-fibrinolytic effects.

JB170 is a highly efficient and specific Aurora A degradator (DC50 = 28 nM). The PROTAC is composed of Alisertib and Thalidomide, with an EC50 value for AURORA-A that is ten times that of AURORA-B. It induces S-phase arrest in cell growth and inhibits the non-catalytic function of the AURORA-A kinase.

XL01126, a potent degrader of LRRK2, exhibits DC50 values of 14 nM (G2019S LRRK2) and 32 nM (WT LRRK2), respectively. It has the ability to cross the blood-brain barrier, making it a viable degrader probe for Parkinson's disease research. This compound is instrumental in exploring the non-catalytic and scaffolding functions of LRRK2 [1].

Formate dehydrogenase, a widely present enzyme in both prokaryotes and eukaryotes, facilitates the reversible oxidation of formate to carbon dioxide. Based on its metal content, structure, and catalytic approach, it is classified into two groups: non-metallic and metal-containing, frequently utilized in biochemical research [1].

IGRP(206-214) is an bioactive peptide corresponding to residues 206–214 of the murine islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP). It induces diabetes in non-obese diabetic (NOD) mice by being specific for T cells targeting both proinsulin and IGRP.