covalently

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.

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).

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

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 zero-length crosslinker. EDC hydrochloride is ideal for covalently binding proteins or peptides to carboxyl containing beads, resins, or other nanoparticals.

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.

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.

Z-VEID-FMK is a selective and cell-permeable caspase-6 peptide inhibitor that irreversibly covalently binds to the active site of the enzyme, thereby inhibiting apoptosis and DNA breakage.

Avitinib (AC0010), also known as AC0010 or AC0010MA, is an orally available, irreversible, epidermal growth factor receptor (EGFR) mutant-selective inhibitor, with potential antineoplastic activity. Upon oral administration, avitinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the drug-resistant T790M EGFR mutant, which prevents signaling mediated by mutant forms of EGFR. This may both induce cell death and inhibit tumor growth in EGFR-mutated tumor cells. EGFR, a receptor tyrosine kinase that is mutated in a variety of Ys, plays a key role in tumor cell proliferation and tumor vascularization. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced when compared to non-selective EGFR inhibitors, which also inhibit wild-type EGFR.

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].

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.