Covalent Inhibitor Library

Catalog No. L9410

Library Compound List Excel SDF

Covalent inhibitors are small organic molecules which interact with specific target proteins and form a covalent bond, resulting an alteration of the protein conformation and subsequently inhibit the protein activity. With some exceptions, protein modification by covalent inhibitors is usually irreversible.

Covalent inhibitors possess significant advantages over non-covalent inhibitors, 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. 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. Consequently, there has been a reluctance to apply a covalent mode of action in drug discovery programs and avoided by the pharmaceutical industry.

Although the majority of successful covalent drugs were discovered through serendipity in phenotypic screens, and their molecular mechanisms were elucidated afterwards, covalent drugs have made a major impact on human health and have been highly successful drugs for the pharmaceutical industry over the last 100 years, such as penicillin, omeprazole, clopidogrel, aspirin, fluorouracil, and third generation of irreversible EGFR tyrosine kinase inhibitor AZD9291/Osimertinib.

In recent years, the distinct strengths of covalent inhibitors in overcoming drug resistance had been recognized. It appears that irreversible inhibitors may maintain activity against drug-resistant mutations that are acquired after treatment with reversible inhibitors. Irreversible inhibition has important and potentially advantageous consequences for drug pharmacodynamics in which the level and frequency of dosing relates to the extent and duration of the resulting pharmacological effect. The unique pharmacodynamic feature of covalent inhibitors might bring certain practical advantages. The prolonged duration of drug action on the target effectively uncouples the pharmacodynamics of the drug from the pharmacokinetics of exposure, as target inhibition persists after the drug has been cleared. This property of covalent drugs enables less frequent dosing and the potential for lower drug doses. In addition, more and more studies have found that many major diseases, such as malignant tumors, are regulated by kinases, and these enzymes have also become the most attractive drug targets. Over the past decade, covalent kinase inhibitors (CKI) have seen a resurgence in drug discovery. Current FDA approved CKIs will bring the dawn to cancer chemotherapy. The drug design and optimization of covalent inhibitors has become a hot spot in drug discovery.

The irreversible covalent inhibitor molecule is divided into two parts: a seeker and a warhead. After entering the body, the seeker and the target protein binding site first form a non-covalent interaction, and then the warhead forms an irreversible covalent bond with the nucleophilic residues of target protein. Common warheads include Michael acceptors, Sulfonyl fluoride, disulfide bond, etc.

The structure and mechanism of reversible covalent inhibitors are similar to irreversible covalent inhibitors, but the difference is that the covalent binding to the target protein is reversible. The warheads for reversible covalent inhibitors are reversible nucleophilic addition reaction receptors such as cyano group and ketone carbonyl group. The reversibility of its covalent binding to the target makes its pharmacokinetics fall in between irreversible covalent inhibitors and non-covalent inhibitors. To a certain extent, reversible covalent inhibitors share the advantages of irreversible covalent inhibitors in the prolonged duration of action and the potential for lower drug doses, while reducing the risk of toxicity caused by off-target.

TargetMol collects 1949 small molecules including identified covalent inhibitors and other molecules having covalent reactive groups as warheads, such as chloroacetyl，2-Chloropropionyl，Acryloyl，alkyne，sulfonyl fluoride, acrylamide, ketocarbonyl，disulfide bond, etc.

All products from TargetMol are for Research Use Only. Not for Human or Veterinary or Therapeutic Use.

Pack Size
1 mg
30 μL * 10 mM (in DMSO)
50 μL * 10 mM (in DMSO)
100 μL * 10 mM (in DMSO)
250 μL * 10 mM (in DMSO)

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Product Description

A unique collection of 1949 covalent Inhibitors and other molecules with common warheads like chloroacetyl，2-Chloropropionyl，Acryloyl，sulfonyl fluoride, alkyne，acrylamide, ketocarbonyl，disulfide bond, etc.
Structurally diverse with some covalent inhibitors approved by the FDA
Detailed compound information with structure, target, IC50, and biological activity description
NMR and HPLC/LCMS validated to ensure high purity

Library Customization

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Packaging And Storage

Powder or pre-dissolved DMSO solutions in 96/384 well plate with optional 2D barcode
Shipped with blue ice

Supporting Files

Library Handling Instructions (635 KB) Targetmol Library Catalog (13.2 MB) Request for Library Compostion in Excel and SDF files

Publications Cited TargetMol Libraries

1. European Journal of Pharmacology. 2022: 175035. 2. Cell Stem Cell. 2022 Apr 29(4) 545–558. 3. Science Bulletin. 2022. 4. Science Translational Medicine. 2022, 14(656): eabn3231. 5. Science Advances. 2023, 9(9): eade3760. 6. Nature. 2020, 582: 289-293. 7. Nature Biotechnology. 2021, 39(11): 1444-1452. 8. Nature Communications. 2022, 13(1): 1-15.. 9. Nature Communications. 2023, 14(1): 1020..

10. Nature Communications. 2023, 14(1): 2756.. 11. Blood. 2021, 137(11): 1478-1490. 12. Nucleic Acids Research. 2021. 13. Nature Communications. 2023, 14(1): 7574. 14. Advanced Science. 2020, 7(16): 2000925. 15. Angewandte Chemie. 2021. 16. Acta Pharmaceutica Sinica B. 2022. 17. Protein & Cell. 2021, 12(11): 877-888. 18. Bone Research. 2023, 11(1): 54. 19. Pharmacology & Therapeutics. (2021): 107930. 20. Nature Communications. 2021, 12(1): 1-12. 21. Journal of Cell Biology. 2022, 221(5): e202112024.

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Library Composition

Antibacterial (229)

Apoptosis (228)

Antibiotic (177)

Endogenous Metabolite (170)

Autophagy (141)

EGFR (74)

NF-κB (61)

Reactive Oxygen Species (39)

Antifungal (38)

HIV Protease (37)

VEGFR (35)

Parasite (35)

DNA/RNA Synthesis (32)

COX (29)

Influenza Virus (29)

BTK (28)

Dehydrogenase (27)

Proteasome (27)

PDGFR (26)

Microtubule Associated (23)

P450 (23)

FGFR (23)

Ferroptosis (22)

Raf (22)

Epigenetic Reader Domain (22)

Antioxidant (22)

Calcium Channel (21)

Estrogen/progestogen Receptor (21)

CDK (20)

STAT (20)

Ras (20)

AChR (19)

Anti-infection (19)

c-Kit (19)

ERK (19)

PI3K (19)

JAK (18)

Caspase (18)

Phosphatase (18)

p38 MAPK (17)

HDAC (17)

Nucleoside Antimetabolite/Analog (17)

PKC (17)

SARS-CoV (16)

TRP/TRPV Channel (16)

BCL (15)

FLT (15)

mTOR (15)

ribosome (15)

Potassium Channel (14)

ATPase (14)

Cysteine Protease (14)

Progesterone Receptor (14)

Akt (14)

Src (13)

Histone Methyltransferase (13)

PDE (13)

ROS (13)

HSV (13)

IκB/IKK (12)

MAO (12)

HER (12)

HSP (12)

Phospholipase (12)

Monoamine Oxidase (12)

TNF (12)

PPAR (11)

MMP (11)

Wnt/beta-catenin (11)

Tyrosinase (11)

Glucocorticoid Receptor (11)

Androgen Receptor (11)

c-RET (11)

HIF/HIF Prolyl-Hydroxylase (11)

Adrenergic Receptor (11)

Antiviral (11)

AMPK (11)

DUB (11)

HCV Protease (11)

Nrf2 (10)

AChE (10)

Drug Metabolite (10)

Estrogen Receptor/ERR (10)

JNK (10)

5-HT Receptor (10)

GABA Receptor (10)

TGF-beta/Smad (9)

Virus Protease (9)

IL Receptor (9)

NOS (9)

HBV (9)

Proton pump (9)

Reverse Transcriptase (8)

Mitophagy (8)

P-gp (7)

Bcr-Abl (7)

Mitochondrial Metabolism (7)

GluR (7)

E1/E2/E3 Enzyme (7)

Opioid Receptor (7)

S1P Receptor (7)

Trk receptor (7)

P2Y Receptor (7)

Prostaglandin Receptor (7)

PARP (7)

Beta Amyloid (7)

RAAS (7)

Transferase (7)

Tyrosine Kinases (6)

Retinoid Receptor (6)

DNA Methyltransferase (6)

c-Met/HGFR (6)

Reductase (6)

HIF (6)

CXCR (6)

Glutathione Peroxidase (6)

Interleukin (6)

Lipoxygenase (6)

CCR (6)

IRE1 (6)

Topoisomerase (6)

p53 (6)

Serine Protease (6)

MAPK (6)

NO Synthase (6)

Chloride channel (6)

STING (6)

Integrin (6)

NOD-like Receptor (NLR) (5)

HMG-CoA Reductase (5)

NOD (5)

Antifection (5)

Adenosine Receptor (5)

Sodium Channel (5)

Cannabinoid Receptor (5)

IGF-1R (5)

Histone Acetyltransferase (5)

Immunology/Inflammation related (5)

PKA (5)

Telomerase (5)

FAAH (4)

ALK (4)

PDK (4)

c-Fms (4)

Indoleamine 2,3-Dioxygenase (IDO) (4)

Epoxide Hydrolase (4)

S6 Kinase (4)

Aurora Kinase (4)

PLK (4)

CaMK (4)

Acyltransferase (4)

Hedgehog/Smoothened (4)

DNA Alkylation (4)

PROTAC Linker (4)

CSF-1R (4)

PERK (4)

iGluR (4)

BACE (4)

DNA Alkylator/Crosslinker (4)

Pim (4)

Glucosidase (4)

Carbonic Anhydrase (4)

DPP-4 (4)

Gamma-secretase (3)

CRISPR/Cas9 (3)

Beta-Secretase (3)

BCRP (3)

Mdm2 (3)

GPR (3)

GTPase (3)

Sirtuin (3)

Fatty Acid Synthase (3)

GSK-3 (3)

Hydroxylase (3)

Histone Demethylase (3)

Antifolate (3)

MEK (3)

Aromatase (3)

LPL Receptor (3)

IRAK (3)

P2X Receptor (3)

Thrombin (3)

TAM Receptor (3)

Casein Kinase (3)

Isocitrate Dehydrogenase (IDH) (3)

Aryl Hydrocarbon Receptor (3)

ATM/ATR (3)

Dopamine Receptor (3)

DNA-PK (3)

Smo (3)

RSV (2)

Rho (2)

c-Myc (2)

GPX (2)

Acetyl-CoA Carboxylase (2)

MRP (2)

Pyroptosis (2)

Adenosine deaminase (2)

Tie-2 (2)

Histamine Receptor (2)

Lipase (2)

Cell wall (2)

transporter (2)

Complement System (2)

Ligands for Target Protein for PROTAC (2)

DprE1 (2)

Amino Acids and Derivatives (2)

EBI2/GPR183 (2)

ROR (2)

FAK (2)

MLK (2)

CAT (2)

Adenylyl cyclase (2)

Decarboxylase (2)

Thyroid hormone receptor(THR) (2)

RIP kinase (2)

TLR (2)

NMDAR (2)

UGT (2)

Ephrin Receptor (2)

FLAP (2)

cAMP (2)

Lipid (2)

ATP Citrate Lyase (2)

IDO (2)

Chk (2)

OX Receptor (2)

NAMPT (2)

Leukotriene Receptor (2)

Glucagon Receptor (2)

LRRK2 (2)

CD73 (2)

PAK (2)

FXR (2)

Aminopeptidase (2)

DNA gyrase (1)

Kinesin (1)

Thioredoxin (1)

ACK (1)

Arginase (1)

YAP (1)

Monoamine Transporter (1)

CRM1 (1)

Dynamin (1)

Guanylate cyclase (1)

PKM (1)

CFTR (1)

PROTACs (1)

Xanthine Oxidase (1)

Monocarboxylate transporter (1)

ROS Kinase (1)

MAGL (1)

Vasopressin Receptor (1)

AhR (1)

Transaminase (1)

PTEN (1)

DNA (1)

Neuropeptide Y Receptor (1)

DHFR (1)

cholecystokinin (1)

Somatostatin (1)

MALT (1)

PD-1/PD-L1 (1)

PAD (1)

NPC1L1 (1)

cell cycle arrest (1)

SGK (1)

Neprilysin (1)

RANKL/RANK (1)

Galectin (1)

Glutaminase (1)

ABC (1)

Glucokinase (1)

Hippo pathway (1)

Bombesin Receptor (1)

ROCK (1)

MELK (1)

Liver X Receptor (1)

Serine/threonin kinase (1)

Free radical scavengers (1)

cGAS (1)

CPT (1)

Ligand for E3 Ligase (1)

TOPK (1)

Haspin Kinase (1)

SIK (1)

LTR (1)

PAFR (1)

RAR/RXR (1)

Myosin (1)

Aquaporin (1)

NADPH (1)

Oxytocin Receptor (1)

Glutathione reductase (1)

Necroptosis (1)

gp120/CD4 (1)

PGE Synthase (1)

PI4K (1)

Melanocortin Receptor (1)

KLF (1)

IAP (1)

VDAC (1)

Library Information Sample

Empty	1000025-07-9	1000413-72-8	229005-80-5	1000787-75-6	946387-07-1	1000998-59-3	1175526-27-8	1001288-58-9	1001350-96-4	1001404-83-6	Empty
Empty	Vadadustat	TAK875	TAK-779	Tegobuvir	RN-1734	BMS-687453	AM211	FT011	BMS754807	AAI101	Empty
Empty	1001625-82-6	1001645-58-4	1001753-24-7	1001908-89-9	1002304-34-8	1002-84-2	100291-86-9	100299-08-9	10030-52-1	10040-45-6	Empty
Empty	RPW-24	SRT1720 hydrochloride	INH6	SRT 2183	AMG208	Pentadecanoic acid	Apiopaeonoside	Pemirolast potassium	L-Anserine nitrate salt	Sodium Picosulfate	Empty
Empty	100427-26-7	1004316-88-4	10045-45-1	100462-37-1	1004990-28-6	100-51-6	1005-24-9	1005264-47-0	1005334-57-5	1005342-46-0	Empty
Empty	Lercanidipine	Cobicistat	1-Ethyl-2-benzimidazolinone	ROSIRIDIN	PF-AKT400	Benzyl alcohol	1-Methylnicotinamide chloride	MX69	CVT-10216	LCL161	Empty
Empty	1005491-05-3	100-55-0	1005504-62-0	1005883-72-6	100643-71-8	1007207-67-1	10075-50-0	1007647-73-5	100784-20-1	10083-24-6	Empty
Empty	Tirasemtiv	Roniacol	Rg3039	Z433927330	Desloratadine	CH5132799	5-Bromoindole	Smurf1-IN-A01	Halosulfuron-methyl	Piceatannol	Empty
Empty	100872-83-1	100874-08-6	1009119-64-5	1009119-65-6	100929-71-3	1009298-09-2	1009298-59-2	100929-99-5	1009734-33-1	10097-84-4	Empty
Empty	ML346	SB 4	Daclatasvir	Daclatasvir dihydrochloride	NADPH (tetracyclohexanamine)	AZD8055	Vistusertib	PAβN dihydrochloride	HZ1157	Rotundine	Empty
Empty	1009816-48-1	1009817-63-3	1009820-21-6	100986-85-4	101001-34-7	1010411-21-8	1010-60-2	1011244-68-0	1011301-27-1	1011529-10-4	Empty
Empty	Thiamet G	B-AP15	Silmitasertib	Levofloxacin	Pamicogrel	GSK369796 Dihydrochloride	2-Chloronaphthoquinone	TFAP	Tenovin3	Azvudine	Empty
Empty	101152-94-7	101155-02-6	1011557-82-6	1011-74-1	101-20-2	1012054-59-9	101-21-3	101-26-8	101303-98-4	1013101-36-4	Empty
Empty	Milnacipran hydrochloride	BW-A78U	Tenovin-6	DL-Normetanephrine hydrochloride	Triclocarban	CUDC101	Chlorpropham	Mestinon	Zacopride hydrochloride	PF04691502	Empty
Empty	101-31-5	1013-69-0	1013750-77-0	1013753-99-5	10138-52-0	1013920-15-4	1013937-63-7	1014691-61-2	101477-54-7	101494-95-5	Empty
Empty	L-Hyoscyamine	Noreugenin	ML-030	BC-1382	Gadolinium chloride	Vorolanib	VTP-27999 TFA	GSK0660	Lomerizine hydrochloride	8-CHLOROQUINAZOLIN-4(1H)-ONE	Empty