Ligands organométalliques

<p>Inhibitor of BACE1 protease</p>

<p>Inhibitor of CK2 protein kinase; anti-proliferative</p>

<p>Potent, selective and cell-permeable tool for modulation of O-GlcNAcylation. Ac4GlcNAcF3 is a dual modulator of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Ac4GlcNAcF3 perturbates the GlcNAc cycling as OGT can incorporate GlcNAcF3 onto proteins but subsequently, it cannot be removed by OGA. In a mouse embryogenic fibroblast cell line, Ac4GlcNAcF3 increased the level of protein O-GlcNAcylation.</p>

<p>A selective P2X7 receptor antagonist with an IC50 value of 11.2 nM. Prevents breast cancer resistance protein (BCRP)-mediated transport of methotrexate. Has therapeutic potential for osteoarthritis due to its anti-proliferative and pain-relieving effects.</p>

<p>A prodrug of the DNA-intercalating agent daunorubicin with anti-tumoral activity, used for suicide gene therapy and activity-dependent ablation of cells. Daun02 is an inactive form of the toxin, which gets activated upon cleavage with prodrug-activating enzyme β-galactosidase, yielding daunorubicin. Genetic constructs have been designed carrying the lacZ gene, coding for β-galactosidase, under control of application-specific promoters. The cells expressing the β-gal undergo cell death since the enzyme hydrolizes the prodrug into the active toxin.</p>

<p>Sildenafil is a potent inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5), consequently preventing the degradation of cGMP in the smooth muscle cells of the pulmonary vasculature and penis. For this reason Sildenafil can be used to increase blood flow, decrease inflammation and mucus production in the lungs and also can be used in the treatment of erectile dysfunction in men. This is largely due to the increased availability of cGMP which can cause the relaxation of the smooth muscles to be prolonged.</p>

<p>Losartan is an angiotensin receptor drug that is used to treat hypertension. It works by blocking the activity of angiotensin II binding to the AT1 receptor. As a result, this causes vascular smooth muscle relaxation and lowers blood pressure.</p>

<p>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.</p>

<p>Inhibitor of pan-class I PI3K family of lipid kinases; antineoplastic</p>

<p>NBQX is a competitive antagonist of ionotropic glutamate receptors of AMPA and kainate subfamilies. It has been reported anti-convulsant activity in seizures models induced by electrostimulation, drugs or genetic predisposition. It has also exhibited pro-convulsant effects in Theiler's murine encephalomyelitis virus-induced (TMEV) seizure model.</p>

<p>Inhibitor of TGF-α, CTGF, ERK1/2, NF-κB and FasL; anti-inflammatory</p>

<p>Competitive oxytocin receptor antagonist. Inhibits oxytocin-induced uterine contractions in vitro and in in vivo models of preterm labor.  Acts via Gαi signalling and activates NF-κB and MAPK pathways to elicit proinflammatory effects in the amnion.</p>

<p>Inhibitor of activin receptor-like kinases (ALK4, ALK5 and ALK7), members of TGFβ type I receptor family. Blocks activin- and TGFβ-mediated signaling and phosphorylation of Smad2 downstream. Suppresses tumor-promoting and tumor-suppressing effects of TGFβ. Promotes differentiation of human embryonic stem cells (hESCs), whilst sustaining mouse ESCs in the undifferentiated state.</p>

<p>Obatoclax mesylate is a synthetic small molecule, which is derived from chemical synthesis with a primary mode of action as a pan-BCL-2 inhibitor. This compound antagonizes multiple anti-apoptotic proteins within the BCL-2 family, ultimately promoting apoptosis in malignant cells. Its ability to inhibit these proteins disrupts the survival mechanisms that cancer cells exploit, potentially restoring apoptotic pathways that are often dysregulated in cancerous tissues.</p>

<p>Ivabradine is a HCN channel blocker that is used to reduce the risk of hospitalization for worsening heart failure and used in the treatment of symptomatic heart failure. This drug acts by inhibiting the “funny” channel pacemaker current (If) which results in a lower heart rate and allows for more blood flow to the myocardium.</p>

<p>CYP17 lyase inhibitor; androgen receptor antagonist</p>

<p>Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) that has been used to treat pain and inflammation. Ketoprofen inhibits the production of inflammatory prostaglandins, which are released by platelets in response to injury or infection. The main mechanism of action is inhibition of cyclooxygenase enzymes COX 1 and COX 2 at the level of transcriptional activation. This results in decreased levels of prostaglandins that mediate pain, fever and inflammation.</p>

<p>Pimavanserin is an atypical antipsychotic drug that is used for the treatment of symptoms associated with Parkinson’s disease. Although this drug’s mechanism of action is not fully understood, it is said to act via inverse agonist at serotonin 5-HT2A receptors to aid with the symptoms.</p>

<p>Troxipide is a gastric cytoprotective agent that is used for the treatment of gastroesophageal reflux disease (GERD). It has anti-inflammatory, anti-ulcer and mucus secreting properties. This drug inhibits proinflammatory mediators in order to restore the normal gastric mucosa.</p>

<p>Potent inhibitor of histone deacetylase 6 (HDAC6), inducing elevated levels of acetylated α-tubulin. It inhibits pro-inflammatory cytokines TNF-α and IL-6 as well as nitric oxide secretion in human and murine macrophages. It is not neurotoxic and it rescues cognitive impairment in mice model for Alzheimer’s disease.</p>