irreversible inhibition

By Targets:	Apoptosis (3) Cathepsin (3) CCR (1) Cytochrome P450 (2) Deubiquitinase (1) DNA Alkylator/Crosslinker (1) DNA Methyltransferase (2) DNA/RNA Synthesis (1) EGFR (1) Epigenetic Reader Domain (1) Filovirus (1) Glutathione Peroxidase (1) HSV (2) MALT1 (1) Monoamine Oxidase (1) mTOR (1) Nucleoside Antimetabolite/Analog (2) Parasite (1) Potassium Channel (1) SARS-CoV (3) SphK (1) Wnt (1) YAP (1)
By Research Areas:	Cancer (11) Infection (5) Inflammation/Immunology (2) Metabolic Disease (1) Neurological Disease (1)
Click Chemistry:	Azide (1)

Cat. No.	Product Name	Target	Research Areas	Chemical Structure

HY-155338

SWTX-143	YAP	Cancer
SWTX-143 is a novel covalent YAP/TAZ-TEAD inhibitor that binds to the palmitoylation pocket of all four TEAD isoforms. SWTX-143 causes irreversible and specific inhibition of the transcriptional activity of YAP/TAZ-TEAD and shows antitumor activity .

HY-13822

SKI II 2 Publications Verification	SphK Wnt Apoptosis	Cancer
SKI-II is an oral active and synthetic inhibitor of sphingosine kinase (SK) activity, with IC₅₀ values of 78 μM and 45 μM for SK1 and for SK2, respectively. SKI II causes an irreversible inhibition of SK1 by inducing its lysosomal and/or proteasomal degradation .

HY-W014134

p-APMSF hydrochloride p-Amidinophenylmethylsulfonylfluoride hydrochloride	Others	Others
p-APMSF is an irreversible inhibitor of serinase. p-APMSF has substrate specificity for positively charged side chains of amino acids, lysine, or arginine. p-APMSF can be used to study the irreversible inhibition of trypsin and thrombin .

HY-W019847

Azamulin	Cytochrome P450	Infection Metabolic Disease
Azamulin is an irreversible, highly selective inhibitior of human CYP3Aa. Azamulin has CYP3A inhibition activity with IC₅₀ values range from 0.03-0.24 μM. Azamulin can be used for the research of metabolism and antiinfection .

HY-114577

Palifosfamide tromethamine Isophosphoramide mustard tromethamine; IPM tromethamine; ZIO-201 tromethamine	DNA Alkylator/Crosslinker	Cancer
Palifosfamide (tromethamine) is a synthetic alkylating agent with potential antineoplastic activity. As the stabilized active metabolite of ifosfamide, palifosfamide (tromethamine) irreversibly alkylates and crosslinks DNA through GC base pairs. This leads to an inhibition of DNA replication and ultimately cell death. Compared to ifosfamide, palifosfamide (tromethamine) is less toxic.

HY-133118

6RK73 2 Publications Verification	Deubiquitinase	Cancer
6RK73 is a covalent irreversible and specific UCHL1 inhibitor with an IC₅₀ of 0.23 µM. 6RK73 shows almost no inhibition of UCHL3 (IC₅₀=236 µM). 6RK73 specifically inhibit UCHL1 activity in breast cancer .

HY-119293

K777 1 Publications Verification	Cathepsin CCR Cytochrome P450 Parasite SARS-CoV Filovirus	Infection Cancer
K777 is a potent, orally active and irreversible cysteine protease inhibitor. K777 is also a potent CYP3A4 inhibitor with an IC₅₀ of 60 nM and a selective CCR4 antagonist featuring the potent chemotaxis inhibition. K777 irreversibly inhibits Cruzain, the major cysteine protease of Trypansoma cruzi, and cathepsins B and L. K777 is a broad-spectrum antiviral by targeting cathepsin-mediated cell entry. K777 inhibits SARS-CoV and EBOV pseudovirus entry with IC₅₀ values of 0.68 nM and 0.87 nM, respectively .

HY-124069

M-525	Epigenetic Reader Domain	Cancer
M-525 is a first-in-class, highly potent, irreversible and covalent menin-MLL protein-protein interaction inhibitor. M-525 binds to menin with an IC₅₀ of 3 nM and achieves low nanomolar potencies in cell growth inhibition and in suppression of MLL regulated gene expression in MLL leukemia cells. Anti-leukemia activity .

HY-147691

MPO-IN-5	Glutathione Peroxidase Potassium Channel	Inflammation/Immunology
MPO-IN-5 (compound 1) is a potent, irreversible MPO (myeloperoxidase) inhibitor. MPO-IN-5 inhibits MPO peroxidation and hERG binding, with IC₅₀ values of 0.22 and 2.8 μM, respectively. MPO-IN-5 shows rapid kinetics of inhibition, with enzyme inactivation rate (k_inact/K_i) of 23000 M ⁻¹s ⁻¹ .

HY-A0004

Decitabine Maximum Cited Publications 87 Publications Verification 5-Aza-2'-deoxycytidine; 5-AZA-CdR; NSC 127716	DNA Methyltransferase Apoptosis Nucleoside Antimetabolite/Analog	Cancer
Decitabine (NSC 127716) is an orally active deoxycytidine analogue antimetabolite and a DNA methyltransferase inhibitor. Decitabine incorporates into DNA in place of cytosine can covalently trap DNA methyltransferase to DNA causing irreversible inhibition of the enzyme. Decitabine induces cell G2/M arrest and cell apoptosis. Decitabine has potent anticancer activity .

HY-108137

Z-LVG-CHN2 2 Publications Verification	Cathepsin HSV SARS-CoV	Infection Inflammation/Immunology
Z-LVG-CHN2 is a cell-permeable and irreversible inhibitor of cysteine proteinase. Z-LVG-CHN2 is a tripeptide derivative and mimics part of the human cysteine proteinase-binding center. Z-LVG-CHN2 displays an inhibition on HSV whereas no significant effect on poliovirus replication. Z-LVG-CHN2 effectively blocks SARS-COV-2 replication (EC₅₀=190 nM) via inhibition of SARS-COV-2 3CL pro protease .

HY-18953

mTOR inhibitor-23	mTOR	Cancer
mTOR inhibitor-23 (compound DHM25) is a selective, competitive, irreversible and covalent inhibitor of mTOR. mTOR inhibitor-23 has the mechanism of inhibition occurs mainly through its capacity to covalently interact with a nucleophilic amino acid inside the ATP pocket. mTOR inhibitor-23 exerts potent antitumor activity against triple-negative breast tumor cell lines .

HY-12276

MALT1 inhibitor MI-2 4 Publications Verification	MALT1	Cancer
MALT1 inhibitor MI-2 is a MALT1 inhibitor (IC₅₀=5.84 μM). MALT1 inhibitor MI-2 binds directly to MALT1, irreversibly suppresses protease function and is accompanied by NF-κB reporter activity suppression, c-REL nuclear localization inhibition, and NF-κB target gene downregulation. MALT1 inhibitor MI-2 shows nontoxic to animals .

HY-A0004R

Decitabine (Standard) 5-Aza-2'-deoxycytidine (Standard); 5-AZA-CdR (Standard); NSC 127716 (Standard)	DNA Methyltransferase Apoptosis Nucleoside Antimetabolite/Analog	Cancer
Decitabine (Standard) is the analytical standard of Decitabine. This product is intended for research and analytical applications. Decitabine (NSC 127716) is an orally active deoxycytidine analogue antimetabolite and a DNA methyltransferase inhibitor. Decitabine incorporates into DNA in place of cytosine can covalently trap DNA methyltransferase to DNA causing irreversible inhibition of the enzyme. Decitabine induces cell G2/M arrest and cell apoptosis. Decitabine has potent anticancer activity .

HY-108137A

Z-L(D-Val)G-CHN2	Cathepsin HSV SARS-CoV	Infection
Z-L(D-Val)G-CHN2 is the isoform of Z-LVG-CHN2 (HY-108137). Z-LVG-CHN2 is a cell-permeable and irreversible inhibitor of cysteine proteinase. Z-LVG-CHN2 is a tripeptide derivative and mimics part of the human cysteine proteinase-binding center. Z-LVG-CHN2 displays an inhibition on HSV whereas no significant effect on poliovirus replication. Z-LVG-CHN2 effectively blocks SARS-COV-2 replication (EC₅₀=190 nM) via inhibition of SARS-COV-2 3CL pro protease .

HY-111553

TAS0728	EGFR	Cancer
TAS0728 is a potent, selective, orally active, irreversible and covalent-binding HER2 inhibitor, with an IC₅₀ of 13 nM. TAS0728 also shows IC₅₀s of 4.9, 8.5, 31, 65, 33, 25 and 86 nM for BMX、HER4、BLK、EGFR、JAK3、SLK and LOK respectively. Furthermore, TAS0728 exhibits robust and sustained inhibition of the phosphorylation of HER2HER3, and downstream effectors .

HY-N1638

1-Methyl-2-undecyl-4(1H)-quinolone	Monoamine Oxidase	Neurological Disease
1-Methyl-2-undecyl-4(1H)-quinolone is a potent, irreversible and selective inhibitor of type B monoamine oxidase (MAO-B). 1-Methyl-2-undecyl-4(1H)-quinolone shows a selective inhibition of MAO-B activity with the IC₅₀ and K_i values of 15.3 μM and 9.91 μM, respectively, but did not inhibit type A MAO (MAO-A) activity. Methyl-2-undecyl-4(1H)-quinolone, as a quinolone alkaloid, is isolated from fresh leaves and fruits of Evodia rutaecarpa HOOK. f. et THOMS .

HY-134318B

8-Azido-ADP disodium	DNA/RNA Synthesis	Others
8-Azido-ADP (disodium) is a covalent-binding inhibitor of mitochondrial adenine nucleotide translocation. 8-Azido-ADP (disodium) causes irreversible inhibition of adenine nucleotide exchange in a light-dependent reaction. 8-Azido-ADP (disodium) inhibits the normal state 4 → 3 transitions of mitochondrial respiration induced by ADP . 8-Azido-ADP (disodium) is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. Strain-promoted alkyne-azide cycloaddition (SPAAC) can also occur with molecules containing DBCO or BCN groups.

Cat. No.	Product Name

HY-L036P

Covalent Screening Library Plus	2,996 compounds
Small molecule covalent inhibitors, or irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity, such that covalent warheads can target rare residues of a particular target protein, thus leading to the development of highly selective inhibitors and achieving a more complete and continued target occupancy in living systems. In recent years, the distinct strengths of covalent inhibitors in overcoming drug resistance had been recognized. However, toxicity can be a real challenge related to this class of therapeutics due to their potential for off-target reactivity and has led to these drugs being disfavored as a drug class. The drug design and optimization of covalent inhibitors has become a hot spot in drug discovery. MCE covalent inhibitor library contains 2,996 small molecules including identified covalent inhibitors and other molecules having common covalent reactive groups as warheads, such as acrylamides, activated terminal acetylenes, sulfonyl fluorides/esters, cloracetamides, alkyl halides, epoxides, aziridines, disulfides, etc. MCE Covalent inhibitor Library plus, with more powerful screening capability, further complement Covalent inhibitor Library (HY-L036) by adding some fragment compounds with covalent warheads.

Covalent Screening Library Plus

2,996 compounds

Small molecule covalent inhibitors, or irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity, such that covalent warheads can target rare residues of a particular target protein, thus leading to the development of highly selective inhibitors and achieving a more complete and continued target occupancy in living systems. In recent years, the distinct strengths of covalent inhibitors in overcoming drug resistance had been recognized. However, toxicity can be a real challenge related to this class of therapeutics due to their potential for off-target reactivity and has led to these drugs being disfavored as a drug class. The drug design and optimization of covalent inhibitors has become a hot spot in drug discovery.

MCE covalent inhibitor library contains 2,996 small molecules including identified covalent inhibitors and other molecules having common covalent reactive groups as warheads, such as acrylamides, activated terminal acetylenes, sulfonyl fluorides/esters, cloracetamides, alkyl halides, epoxides, aziridines, disulfides, etc.

MCE Covalent inhibitor Library plus, with more powerful screening capability, further complement Covalent inhibitor Library (HY-L036) by adding some fragment compounds with covalent warheads.

HY-L036

Covalent Screening Library	1,676 compounds
Small molecule covalent inhibitors, or irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity, such that covalent warheads can target rare residues of a particular target protein, thus leading to the development of highly selective inhibitors and achieving a more complete and continued target occupancy in living systems. In recent years, the distinct strengths of covalent inhibitors in overcoming drug resistance had been recognized. However, toxicity can be a real challenge related to this class of therapeutics due to their potential for off-target reactivity and has led to these drugs being disfavored as a drug class. The drug design and optimization of covalent inhibitors has become a hot spot in drug discovery. MCE covalent inhibitor library contains 1,676 small molecules including identified covalent inhibitors and other bioactive molecules having common covalent reactive groups as warheads, such as acrylamides, activated terminal acetylenes, Sulfonyl fluorides/esters, cloracetamides, alkyl halides, epoxides, aziridines, disulfides, etc.

Covalent Screening Library

1,676 compounds

Small molecule covalent inhibitors, or irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity, such that covalent warheads can target rare residues of a particular target protein, thus leading to the development of highly selective inhibitors and achieving a more complete and continued target occupancy in living systems. In recent years, the distinct strengths of covalent inhibitors in overcoming drug resistance had been recognized. However, toxicity can be a real challenge related to this class of therapeutics due to their potential for off-target reactivity and has led to these drugs being disfavored as a drug class. The drug design and optimization of covalent inhibitors has become a hot spot in drug discovery.

MCE covalent inhibitor library contains 1,676 small molecules including identified covalent inhibitors and other bioactive molecules having common covalent reactive groups as warheads, such as acrylamides, activated terminal acetylenes, Sulfonyl fluorides/esters, cloracetamides, alkyl halides, epoxides, aziridines, disulfides, etc.

Cat. No.	Product Name	Target	Research Area

HY-P10244F

Biotin-YVAD-FMK	Peptides	Infection
Biotin-YVAD-FMK is an inhibitor for vacuolar processing enzyme (VPE), with a 64% inhibition at 5 μM. Biotin-YVAD-FMK is an irreversible substrate for caspase 1 .

Cat. No.	Product Name	Category	Target	Chemical Structure

HY-N1638

1-Methyl-2-undecyl-4(1H)-quinolone	Alkaloids Source classification Evodia rutaecarpa (Juss.) Benth. Rutaceae Quinoline Alkaloids Plants	Monoamine Oxidase
1-Methyl-2-undecyl-4(1H)-quinolone is a potent, irreversible and selective inhibitor of type B monoamine oxidase (MAO-B). 1-Methyl-2-undecyl-4(1H)-quinolone shows a selective inhibition of MAO-B activity with the IC₅₀ and K_i values of 15.3 μM and 9.91 μM, respectively, but did not inhibit type A MAO (MAO-A) activity. Methyl-2-undecyl-4(1H)-quinolone, as a quinolone alkaloid, is isolated from fresh leaves and fruits of Evodia rutaecarpa HOOK. f. et THOMS .

Cat. No.	Product Name		Classification

HY-134318B

8-Azido-ADP disodium		Azide
8-Azido-ADP (disodium) is a covalent-binding inhibitor of mitochondrial adenine nucleotide translocation. 8-Azido-ADP (disodium) causes irreversible inhibition of adenine nucleotide exchange in a light-dependent reaction. 8-Azido-ADP (disodium) inhibits the normal state 4 → 3 transitions of mitochondrial respiration induced by ADP . 8-Azido-ADP (disodium) is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. Strain-promoted alkyne-azide cycloaddition (SPAAC) can also occur with molecules containing DBCO or BCN groups.

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