Modulateurs d'enzymes

A selective inhibitor of MEK5 protein kinase with an IC50 value of 4.3 nM. Blocks transcriptional activation of myocyte-specific enhancer factor 2C (MEF2C). Inhibits phosphorylation of ERK5 protein kinase and thereby reverses inhibition of TNF signaling induced by fluid shear stress in endothelial cells. Induces apoptosis in FLT3-ITD cells.

Inhibitor of Rho-kinases

Reversible inhibitor of trypsin

VEGFR tyrosine kinase inhibitor

Inhibits non-receptor tyrosine kinase BTK; antineoplastic

Inhibits interaction between small GTPase Rab27a and its effector JFC1 (synaptotagmin-like protein1, Slp1). These proteins regulate neutrophil exocytosis, decrease neutrophil infiltration in liver and kidneys and reduce extracellular ROS production by NAPDH oxidase. Thus, nexinhibib20 suppresses systemic inflammation.

Sorafenib is a drug that belongs to the class of multikinase inhibitors. It inhibits a number of kinases, including the Mcl-1 protein, which is involved in apoptosis along with blocking picolinic acid (PA), an endogenous metabolite involved in apoptosis signal transduction. Sorafenib also binds to epidermal growth factor receptor (EGFR) on the surface of cancer cells, inhibiting the production of proteins that are required for angiogenesis, thus blocking the formation of new blood vessels. Sorafenib may also inhibit P-glycoprotein (Pgp) activity. Overall, these cytotoxic effects give Sorafenib anti-tumor properties, inhibiting angiogenesis and cellular transformation, which are the two main processes of tumor growth and metastasis. Sorafenib tosylate has been shown to be effective against a range of solid tumors such as breast, prostate and lung cancers and is also used for the treatment of metastatic colorectal cancer and renal cell carcinoma. A combination therapy group found that sorafenib was more effective when used with interferon alfa-2b for the treatment of advanced renal cell carcinoma. Sorafenib also has the potential for drug interactions with other drugs that are metabolized by cytochrome P450 enzymes.

Carmofur is an antineoplastic agent that is used to treat various cancers such as breast and colorectal cancer. This drug is a derivative of fluorouracil. Carmofur is an inhibitor of the human acid ceramidase, a lysosomal amidase involved in the development of cancer cells.

A specific inhibitor of Bone Morphogenetic Protein (BMP) type 1 receptors ALK2 and ALK3 (IC50  < 0.5 µM). Dorsomorphin analog that exclusively targets the BMP but not VEGF signaling. It is able to inhibit the BMP-induced Smad1/5/8 activation but not the p38/MAP kinase signaling or Activin A-induced Smad2 activation.

Inhibits isocitrate dehydrogenase 1 (IDH-1) harbouring a gain of function mutation at R132, which causes impaired cellular differentiation via epigenetic modulation. By inhibiting mutant IDH1, synthesis of oncometabolite 2-hydroxyglutarate is reduced. This compound therefore has therapeutic potential in solid and haematological malignancies, such as acute myeloid leukemia (AML).

An irreversible GSK-3β inhibitor that reduces phosphorylation of tau proteins, protects from neuronal loss and has cognitive and behavioural benefits in murine models. Studied for its potential as a therapeutic agent in Alzheimer’s disease and other neurodegenerative diseases. Tideglusib was also shown to inhibit the main protease Mpro from the SARS-CoV-2 virus with IC50 of 1.55 μM.

Monoamine oxidase-B inhibitor; anti-parkinsonian; neuroprotective

Inhibitor of proteaseγ‐secretase, which allows to modulate of the activity of γ‐secretase substrates Notch, E-cadherin, ErbB4, and amyloid precursor protein (APP). The compound can inhibit the growth of tongue carcinoma cells by arresting cell cycle in G0–G1 phase, modulate the activity of Notch1 receptor and Caspase-3 protease and induce apoptosis. It was also demonstrated that this inhibitor reduces the levels of β-amyloid peptide in the brain of mice model for Alzheimer’s disease. This compound also enhances the neuronal differentiation embryonic cells.

Proteosome inhibitor; pro-apoptotic; has anti-myeloma activity

A potent and selective c-Met inhibitor. Anti-tumour activity demonstrated in xenograft models in vivo. Forms a thioether conjugate by reacting with thiol groups in proteins. Non-small-cell lung carcinoma (NSCLC) tumour cells that overexpress c-MET have increased sensitivity to AMG458.

Histone acetyltransferase inhibitor of p300/CBP; anti-proliferative

Inhibits tankyrase (TNKS1 and TNKS2 with IC50 values of 11 and 4 nM respectively), by binding to the catalytic poly-ADP-ribose polymerase (PARP) domain. This stabilizes cytoplasmic protein Axin, mediating β-catenin depletion and thereby suppresses Wnt signalling pathway. XAV 939 has anti-proliferative and pro-apoptotic effects on neuroblastoma and colorectal cancer cells.

Fludarabine triphosphate trisodium is a nucleotide analog, which is a type of chemotherapy agent derived from purine nucleosides. This compound is the active metabolite of fludarabine, sourced from synthetic chemistry designed to mimic naturally occurring nucleotides involved in DNA replication. The mode of action involves its incorporation into the DNA strand during replication, where it effectively inhibits DNA polymerase and ribonucleotide reductase. This disruption impairs DNA synthesis, leading to apoptosis or programmed cell death, particularly in rapidly dividing cancer cells.