non-catalytic

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

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).

FT671 is a non-covalent, selective USP7 inhibitor (IC50=52 nM) that binds to the catalytic domain of USP7 (Kd=7.8 µM). It disrupts the stability of USP7 substrates including MDM2, elevates p53, induces p21, and inhibits tumor growth in mice.

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 a triazolide selective inhibitor of the karrikin (KAR) receptor KAI2 that binds non-covalently to the catalytic pocket of KAI2 and has no significant effect on the related receptor AtD14. KK181N1 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.

AurkA allosteric-IN-1 (compound 6h) is an Aurora A (AurkA) inhibitor with an IC50 of 6.50 μM, which inhibits both the catalytic and non-catalytic activities of Aurora A. Aurora A is involved in the regulation of bipolar mitotic spindle assembly and the fidelity of chromosome segregation during mitosis. AurkA allosteric-IN-1 interferes with Aurora A by binding to the Y-pocket, thereby preventing its interaction with the activator TPX2.

PROTACFAKdegrader 3 is a selective FAK PROTAC degrader (DC50 = 1.08 nM). It induces FAK degradation through the ubiquitin-proteasome system and its interaction with FAK and CRBN. By inhibiting FAK's non-catalytic activity, PROTACFAKdegrader 3 enhances MHC-I gene transcription and tumor cell surface expression, leading to increased antigen presentation and activation of cytotoxic CD8 T cells. Its ability to promote MHC-I expression and boost T cell activation strengthens its antitumor efficacy in vivo. PROTACFAKdegrader 3 is applicable to cancer research targeting FAK degradation, including studies on ovarian cancer and hepatocellular carcinoma.

Xanthine oxidase-IN-17 is a potent xanthine oxidase (XOD) inhibitor with an IC50 of 298 nM and a Ki of 167 nM. By inhibiting the catalytic activity of XOD, it reduces uric acid production and subsequently decreases the formation of O₂⁻ free radicals. Xanthine oxidase-IN-17 is non-cytotoxic in AML-12 liver cells while effectively inhibiting uric acid formation. It is suitable for research on hyperuricemia and gout.

LFM-A13 is a highly selective inhibitor of the non-receptor tyrosine kinase BTK (Bruton's tyrosine kinase) (IC50 = 2.5 μM). It irreversibly severs the downstream signaling network of the B-cell receptor (BCR) by targeted binding to the BTK kinase catalytic domain, exhibiting excellent anti-leukemic and immunomodulatory effects in models of acute/chronic lymphocytic leukemia and severe autoimmune diseases.

MU262 is a structurally novel polycyclic heterocyclic small-molecule compound and a MUS81 inhibitor with an IC₅₀ value of 0.87 μM, which directly inhibits MUS81 catalytic activity through non-interfering DNA binding, inducing genomic instability in tumor cells and specifically inhibiting the HR/BIR repair pathways. MU262 can serve as a chemical biology tool for studying MUS81 function and as a lead compound for developing anticancer therapies that exploit DNA repair defects in cancer cells.

NGI-189 is a selective OST-A inhibitor. Its main mechanism is to inhibit the activity of the STT3A catalytic subunit in the OST complex, thereby reducing the N-glycosylation level of target glycoproteins. It effectively blocks the conduction of oncogenic and bypass signaling pathways, significantly downregulates the phosphorylation levels of EGFR, AKT, p70S6K and S6RP proteins, and induces cell cycle arrest and apoptosis. In non-small cell lung cancer (NSCLC) xenograft models, NGI-189 significantly inhibits tumor growth and induces tumor regression, making it a potential tool molecule for mechanism and efficacy research of EGFR-mutant non-small cell lung cancer.

PROTACEZH2 Degrader-9 is an orally active EZH2 PROTAC degrader, operating through the ubiquitin-proteasome pathway. It effectively reduces the PRC2 core subunit and potently inhibits H3K27me3 without affecting common CRBN neo-substrates, showing selectivity towards GSPT1 and IKZF1/3. The compound exhibits strong antiproliferative effects on various cancer cell lines by inducing cell cycle arrest and apoptosis (apoptosis). Additionally, PROTACEZH2 Degrader-9 reverses PRC2-mediated gene silencing and suppresses the activation of EZH2 non-catalytic target genes. This compound is applicable in research on leukemia, lymphoma, and non-small cell lung cancer.

RM-055 is a novel catalytic RAS(ON) inhibitor that mimics endogenous GAP activity by accelerating GTP hydrolysis and converting active RAS(ON) to inactive RAS(OFF). Through formation of a non-covalent complex with cyclophilin A (CYPA), RM-055 efficiently suppresses oncogenic RAS signaling and demonstrates potent, durable antitumor activity in multiple G12-mutant cancer models.

LpxC-IN-17 (Compound a5) is a non-covalent LpxC inhibitor and antibacterial agent. It chelates catalytic zinc ions and establishes extensive non-covalent interactions within the LpxC active site, functionally inhibiting the enzyme. LpxC-IN-17 exhibits antibacterial activity against Gram-negative pathogens such as Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, and is applicable in studies on Gram-negative bacterial infections.

AcdK is a non-natural amino acid and a precursor of allysine. It can be site-specifically incorporated into target proteins in Escherichia coli using an amber codon suppression strategy. AcdK enables site-specific lysine dimethylation or monomethylation modifications of target proteins. It can synthesize site-specific lysine-methylated variants of histone H3 and p53, which are useful for studying the substrate specificity and catalytic functions of epigenetic enzymes.

RG3039 hydrochloride is an orally active DcpS inhibitor capable of crossing the blood-brain barrier, with an IC50 of 4.2 nM for hDcpS. It inhibits the decapping activity of DcpS, maintaining the enzyme in a non-catalytic conformation within the central nervous system and other tissues. RG3039 hydrochloride extends survival and improves functionality in mouse models of spinal muscular atrophy, making it useful for research related to this condition.

TOP1/TDP1-IN-1 is an inhibitor of DNA topoisomerase 1B (TOP1) and tyrosyl-DNA phosphodiesterase 1 (TDP1) with a TDP1 IC50 of 17.8 μM. It directly inhibits the catalytic activity of TOP1 without forming a DNA-TOP1 ternary complex. This compound disrupts TDP1-mediated TOP1-induced DNA damage repair, exhibits low acute toxicity, and interferes with DNA repair pathways. It induces apoptosis, inhibits clonogenic capacity, and produces antiproliferative effects in cancer cells. TOP1/TDP1-IN-1 can be utilized in research on non-small cell lung cancer, cervical cancer, and colon cancer.

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.