Irreversible

PF-06459988 is a novel, effective, orally active, irreversible, and selective epidermal growth factor receptor (EGFR) mutant inhibitor. PF-06459988 has high efficiency and high affinity for EGFRs double mutants containing T790M, and has minimal activity against WT EGFR. PF-06459988 makes a candidate drug for the treatment of cancer.

4-Diethylaminobenzaldehyde, a reversible aldehyde dehydrogenase (ALDH) inhibitor (Ki: 4 nM for ALDH1), exhibits a potent anti-androgenic effect (IC50: 1.71 μM).

Fenclonine (CP-10188) is a selective and irreversible inhibitor of tryptophan hydroxylase, a rate-limiting enzyme in the biosynthesis of serotonin (5-HYDROXYTRYPTAMINE). Fenclonine(CP-10188) acts pharmacologically to deplete endogenous levels of serotonin.

Sulbactam sodium (CP-45899-2) (Unasyn) is an irreversible β-lactamase inhibitor.

Sulbactam (CP45899) is a semi-synthetic beta-lactamase inhibitor. The beta-lactam ring of sulbactam irreversibly binds to beta-lactamase at or near its active site, thereby blocking enzyme activity and preventing metabolism of other beta-lactam antibiotics by the enzyme. Combining this agent with a beta-lactamase susceptible antibiotic, such as penicillins or a cephalosporin, to treat infections caused by beta-lactamase producing organisms, results in a decreased turnover rate of the beta-lactamase sensitive antibiotic and enhances its antibacterial activity.

YKL-5-124, a potent, selective and covalent CDK7 inhibitor with an IC50 of 9.7 nM, 1300 nM and 3020 nM for CDK7 Mat1 CycH, CDK2 and CDK9 respectively, displays biochemical and cellular selectivity for CDK7 over CDK12 13.

Oritinib (SH-1028) is an inhibitor of EGFR with IC50s of 18, 0.7, 4, 0.1, 1.4 and 0.89 nM for EGFR (wt), EGFR (L858R), EGFR (L861Q), EGFR (L858R T790M), EGFR (d746-750), EGFR (d746-750 T790M), respectively. Oritinib can be used in studies about the treatment of non-small cell lung cancer.

Ibrutinib (PCI-32765) is an irreversible inhibitor of BTK (IC50: 0.5 nM) that selectively blocks B cell activation.

Osimertinib (AZD-9291) is an EGFR third-generation inhibitor that inhibits the T790M resistance mutation produced by second-generation EGFR inhibitors with irreversible and oral activity. Osimertinib has antitumor activity for the treatment of EGFR-mutated non-small-cell lung cancer.

JNK-IN-8 (JNK Inhibitor XVI) is an irreversible JNK1 2 4 inhibitor (IC50: 4.7 18.7 1 nM) with over 10-fold selectivity compared to MNK2 and Fms, and no inhibition of Met, c-Kit, or PDGFRβ in the A375 cell line.

Z-VAD(OMe)-FMK is a pan-caspase inhibitor with irreversible properties; Z-VAD(OMe)-FMK is also an inhibitor of ubiquitin C terminal hydrolase L1 (UCHL1), which is irreversibly modified by targeting the UCHL1 active site.

Emricasan (IDN-6556) is a pan-caspase inhibitor with irreversible properties. Emricasan has anti-inflammatory and anti-apoptotic activity and can be used in the treatment of infections and liver failure, etc. Emricasan also inhibits Zika virus infections.

Diphenyleneiodonium chloride (DPI)(DPI) is an irreversible inhibitor of iNOS and eNOS (IC50 values of 50 nM and 0.3 μM, respectively),and displays broad-spectrum bactericidal activity.

6RK73 is a covalent, irreversible, and specific UCHL1 inhibitor (IC50: 0.23 µM) with almost no inhibition of UCHL3 (IC50: 236 µM).

CHMFL-EGFR-202 is a potent, irreversible inhibitor of EGFR mutant kinase with IC50 values of 5.3 nM for drug-resistant mutant EGFR T790M and 8.3 nM for WT EGFR kinases.

Corin is an irreversible inhibitor of HDAC1(IC50 = 147 nM) and LSD1(Ki = 110 nM).

EGFR-IN-1 hydrochloride is an irreversible and specific inhibitor of L858R T790M mutant EGFR, with 100-fold selectivity over wild-type EGFR. It exhibits potent antitumor and antiproliferative activity in H1975 cells and mutant HCC827 cells with IC50s of 4 and 28 nM, respectively.

Sulfosuccinimidyl oleate (Sulfo-N-succinimidyl oleate) is a long-chain fatty acid that inhibits fatty acid transport into cells. It is a potent and irreversible inhibitor of the mitochondrial respiratory chain and binds the CD36 receptor on the surface of microglia. Sulfosuccinimidyl oleate is neuroprotective and alleviates stroke-induced neuroinflammation [1] [2].

Sulfosuccinimidyl oleate sodium is a long-chain fatty acid that inhibits fatty acid transport into cells and is a potent and irreversible inhibitor of the mitochondrial respiratory chain and has anti-inflammatory properties without causing cytotoxic effects.

T-448 is a specific, orally active, and irreversible inhibitor of lysine-specific demethylase 1 (LSD1, an H3K4 demethylase) with an IC50 of 22 nM.

FMK 9a is an irreversible inhibitor of ATG4B with IC50 values of 80 and 73 nM in the TR-FRET and cellular-based LRA assays.

K777 is a potent, orally active, and irreversible inhibitor of cysteine protease, functioning as a potent CYP3A4 inhibitor (IC50 = 60 nM) and a selective CCR4 antagonist, which inhibits chemotaxis. K777 irreversibly inhibits Cruzain, the major cysteine protease of Trypanosoma cruzi, and cathepsins B and L, targeting cathepsin-mediated cell entry and exhibiting broad-spectrum antiviral activity. It inhibits EBOV and SARS-CoV pseudovirus entry with IC50 values of 0.87 nM and 0.68 nM, respectively.

α-(difluoromethyl)-DL-Arginine (RMI 71897) is an enzyma-activated, irreversible inhibitor of arginine decarboxylase for E. coli (Ki = 800 μM), Pseudomonas aeruginosa, and Klebsiella pneumoniae. At 0.01 mM, it has been shown to prevent osmotic stress-induced increases in arginine decarboxylase activity and putrescine synthesis in oat leaf cells. When combined with a variety of polyamine analogues, α-(difluoromethyl)-DL-Arginine inhibited the growth of Trypanosoma Crui in mammalian host cells at a minimum concentration of 10 mM and prevented the growth of Trypanosoma Crui in T-cell receptor alpha-deficient mouse models.

FIIN-1 (FGFR irreversible inhibitor-1) is an irreversible and selective FGFR inhibitor with Kd of 2.8, 6.9, 5.4, 120, 32 and 120 nM for FGFR1, FGFR2, FGFR3, FGFR4, Flt1, Flt14, respectively.FIIN-1 inhibited FGFR1, FGFR2, FGFR3, FGFR4, with IC50 of 9.2, 6.2, 11.9 and 189 nM. FIIN-1 inhibited FGFR1, FGFR2, FGFR3 and FGFR4, with IC50s of 9.2, 6.2, 11.9 and 189 nM, respectively.