covalently

Epoxomicin (BU-4061T,Aids010837) is a selective proteasome inhibitor with anti-inflammatory activity, inhibits primarily the CH-L activity of the 20S proteasome, while T-L and PGPH catalytic activities are also inhibited at 100- and 1000-fold reduced rate.

H-151 is a highly potent and selective STING antagonist. H-151 covalently binds to Cys91 of STING and inhibits palmitoylation of Cys91, thereby inhibiting STING activity. H-151 can be used in the study of autoinflammatory diseases in vivo and ex vivo.

QL-X-138 is a potent and selective BTK and MNK dual kinase inhibitor that binds covalently to BTK and non-covalently to MNK. The IC50 values of QL-X-138 are 9.4 nM for BTK, 107.4 nM for MNK1, 26 nM for MNK2, and 3.5 μM against Dengue 2. QL-X-138 is used in the study of B-cell malignancies and B-cell malignant tumors.

QL-X-138 HCl is a novel selective and highly potent BTK/MNK dual-kinase inhibitor with anticancer activity that binds covalently to BTK and noncovalently to MNK. QL-X-138 HCl inhibited BTK, MNK1, and MNK2 kinases. QL-X-138 HCl has anti-dengue virus 2 activity and shows anti-proliferative activity in acute myeloid leukemia cells. QL-X-138 HCl can be used to study lymphoma and leukemia.

JAK3-IN-11 (Compound 12) exhibits potent, noncytotoxic, irreversible, orally active JAK3 inhibitory activity (IC50 = 1.7 nM) with an excellent selectivity profile (>588-fold compared to other JAK isoforms), covalently binds to the ATP-binding pocket in JAK3. JAK3-IN-11 strongly inhibits JAK3-dependent signaling and T-cell proliferation which is a promising tool for studying autoimmune diseases [1].

1-Aminohydantoin hydrochloride is a significant metabolite of furantoin in animal tissues. It binds covalently to tissue proteins, is released under slightly acidic conditions, and can be detected by derivatization with 2-nitrobenzaldehyde forming a nitrophenyl derivative of AHD. It is used in assays to determine veterinary drug residues in meat and milk.

m-PEG12-NHS ester is a PEG backbone PROTAC linker commonly used in the synthesis of PROTAC molecules, and the NHS ester can covalently bind to primary amines (-NH2) on biomolecule.

EDC hydrochloride (EDC-HCl Crosslinker) is a water-soluble carbodiimide compound. EDC hydrochloride, as a condensing agent, forms peptide bonds through the condensation reaction of carboxyl and amino groups and can be used to synthesize peptides with specific sequences and functions. EDC hydrochloride can covalently bind haptens to carrier proteins to form immune antigens, which are used in vaccine research. EDC hydrochloride can react with the 5 'phosphate group of nucleic acids and is used for the labeling of DNA and RNA. EDC hydrochloride can cross-link proteins with nucleic acids and is used to prepare immune cross-links. EDC hydrochloride, as a crosslinking agent, connects the amine-reactive NHS ester of biomolecules with the carboxyl group, which can be used for protein coupling to create hybrid molecules with new properties and functions.

Methoxyamine HCl (Methoxyamine) covalently binds to apurinic/apyrimidinic (AP) DNA damage sites and inhibits base excision repair (BER), which may result in an increase in DNA strand breaks and apoptosis. Methoxyamine is an orally bioavailable small molecule inhibitor with potential adjuvant activity. This agent may potentiate the anti-tumor activity of alkylating agents.

Thioacetamide (TAA) is an indirect hepatotoxin commonly used to induce experimental liver injury. It is metabolized by CYP2E1 into reactive metabolites that covalently bind to proteins and lipids, leading to oxidative stress and centrilobular necrosis, hepatocyte death, and M1/M2 macrophage-dominated inflammation. TAA is widely used to establish models of chronic liver fibrosis, hepatic encephalopathy, and liver cancer.

Myristic acid (Crodacid) , a 14 carbon saturated fatty acid, is a rare molecule in cells and is a substrate of some fatty acid desaturases. This compound has the ability to acylate proteins by covalently binding to the N-terminal glycine residues, in a process called N-terminal myristoylation. Myristoylation of substrate proteins by this fatty acid has the potential to activate and mediate many physiological pathways. Furthermore, saturated fatty acids have been reported to be essential for biological activities of lipopolysaccharides and have demonstrated the ability to induce expression of COX-2 and NFκB (nuclear factor κB) activation.

Avibactam sodium (NXL-104) is a non-β-lactam β-lactamase inhibitor that inhibits TEM-1, P99, and KPC-2 β-lactamases (IC50=8/80/38 nM) covalently and reversibly. Avibactam sodium has antimicrobial activity and can be used to treat urinary tract infections.

2-Bromo-4'-hydroxyacetophenone(PTP Inhibitor I) is a cell-permeable, protein tyrosine phosphatase (PTP) inhibitor that covalently blocks the catalytic domain of the Src homology region 2 domain-containing phosphatase (SHP-1(ΔSH2)) with a Ki value of 43 μM and PTP1B with a Ki value of 42 μM [1]. SHP-1 and PTP1B both have known roles in regulating insulin signaling as well as myeloid and lymphoid cell differentiation, making inhibitors of these phosphatases of interest in diabetes, cancer, allergy, and inflammation research [2].

PTP inhibitor 1 is an inhibitor of cell-permeable protein tyrosine phosphatase (PTP) that covalently binds the catalytic domain of the Src homology region 2 domain-containing phosphatase (SHP-1(ΔSH2)),with Ki of128 μM.

Voxelotor (GBT 440) is a novel hemoglobin S (HbS) polymerization inhibitor primarily used for the treatment of sickle cell disease (SCD) and a cytochrome P450 3A4 inhibitor. Voxelotor targets and covalently binds to the N-terminal valine of the HbS alpha chain, thereby stabilizing sickle cell hemoglobin (HbS).

BPK-29 hydrochloride is a specific ligand that disrupts atypical orphan nuclear receptor NR0B1-protein interactions by covalently modifying C274, impairing the anchorage-independent growth of [KEAP1-mutant cancer cells].

Batabulin (T138067) is an antitumor compound that binds covalently and selectively to a subset of the β-tubulin isotypes, disrupting microtubule polymerization. This disruption affects cell morphology, induces cell-cycle arrest, and ultimately leads to apoptotic cell death.

EN6-mediated ATP6V1A modification decouples the v-ATPase from the Rags, leading to inhibition of mTORC1 signaling, increased lysosomal acidification and activation of autophagy. EN6 clears TDP-43 aggregates, a causative agent in frontotemporal dementia, in a lysosome-dependent manner. EN6 is a small-molecule in vivo activator of autophagy that covalently targets cysteine 277 in the ATP6V1A subunit of the lysosomal the vacuolar H+ ATPase (v-ATPase).

MBC-11 triethylamine has potential to treat tumor-induced bone disease (TIBD), is a first-in-class conjugate of the bone-targeting bisphosphonate etidronate covalently linked to the antimetabolite cytarabine (araC).

MBC-11 trisodium has potential to treat tumor-induced bone disease (TIBD).It is a first-in-class conjugate of the bone-targeting bisphosphonate HEDP covalently linked to the antimetabolite Ara-C.

Tirabrutinib hydrochloride is a potent, highly selective, and irreversible oral BTK inhibitor. Tirabrutinib hydrochloride irreversibly covalently binds to Bruton tyrosine kinase (BTK) in B cells and exhibits potent in vitro cytotoxicity against many types of B cell malignancies, as well as in vivo antitumor activity in mouse models [1].

THZ1-R is a non-covalent active analogue of THZ1, with the acrylamide group removed from THZ1, losing its ability to covalently bind to the C312 cysteine residue of CDK7. Its CDK7 inhibitory activity is weaker than that of THZ1.

BPK-29, a ligand specifically targeting the atypical orphan nuclear receptor NR0B1, disrupts its protein interactions through covalent modification at C274, thereby impairing the anchorage-independent growth of KEAP1-mutant cancer cells.

RA190 inhibits proteasome function by covalently binding to cysteine 88 of ubiquitin receptor RPN13.