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.

Acalabrutinib (ACP-196), also known as ACP-196, is an orally available inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, ACP-196 inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.

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

Allitinib (AST-1306) (AST-1306) has anti-cancer activity,and it is an irreversible EGFR and ErbB2 inhibitor with IC50s of 0.5 and 3 nM, respectively. [1]

MRTX-1257 is a selective, irreversible, and covalent inhibitor of KRAS G12C with an IC50 of 900 pM for KRAS-dependent ERK phosphorylation in H358 cells. MRTX-1257 demonstrated 31% bioavailability in the mouse, with free fraction exposures well above cellular potency, and 77% target engagement in a PK/PD experiment.

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.

Wiskostatin is a selective inhibitor of N-WASP, a ubiquitously expressed member of the Wiskott-Aldrich Syndrome protein (WASp) family that regulates actin polymerization.

RN-1 dihydrochloride is an effective and selective irreversible inhibitor of lysine-specific demethylase 1 (LSD1, IC50 = 70 nM).

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.

IPI-9119 is an orally active, selective, and irreversible FASN inhibitor (IC50 = 0.3 nM).

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.

TED-347 is an irreversible and covalent inhibitor of TEAD4-Yap1 protein-protein interaction(EC50 of 5.9 μM), and inhibits glioblastoma cell viability.

Menin-MLL inhibitor 20 is an irreversible inhibitor of the menin-MLL interaction, exhibiting antitumor activities.

Almonertinib mesylate is an irreversible inhibitor of EGFR tyrosine kinase with high selectivity for EGFR-sensitizing and T790M resistance mutations. Almonertinib mesylate can be used in the non-small cell lung cancer studies.

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.

Piperonylic acid (2H-1,3-benzodioxole-5-carboxylic acid) is a natural molecule bearing a methylenedioxy function that closely mimics the structure of trans-cinnamic acid. Piperonylic acid selectively inactivate the CYP73A P450 subpopulation.

Q-VD-OPh is an irreversible caspase inhibitor with an IC50 value of 48 nM against caspase-7 and between 25 and 400 nM against caspase-1, 3, 8, 9, 10, 12. Q-VD-OPh inhibits HIV infection and can cross the blood-brain barrier.

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 effective JNK inhibitor that inhibits JNK1, JNK2, and JNK3 with IC₅₀ values of 4.7, 18.7, and 1 nM, respectively. JNK-IN-8 offers the advantages of minimal off-target activity, sustained inhibition, and high specificity. JNK-IN-8 primarily acts by blocking the JNK/c-Jun signaling pathway, inhibiting the phosphorylation of the downstream transcription factor c-Jun, thereby regulating the expression of genes associated with inflammatory responses, apoptosis, and stress responses. JNK-IN-8 can be used in research on tumors, inflammation, and neurological diseases.

Etomoxir is an irreversible inhibitor of carnitine palmitoyltransferase 1a (CPT-1a) (IC50=5-20 nM). Etomoxir inhibits fatty acid oxidation by inhibiting CPT-1a, inhibits palmitate oxidation, has an inhibitory effect on adenine nucleotide translocase, and can inhibit macrophage polarization by disrupting CoA homeostasis.

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.