Organometallic Ligands

<p>Acecelofenac is a non-steroidal anti-inflammatory drug that is used in the treatment of osteoarthritis, arthritis, and ankylosing spondylitis. This drug is also a cyclooxygenase inhibitor and works by inhibiting this enzyme so that pain and inflammation is reduced.</p>

<p>Imiquimod maleate is an immune response modifier, which is a synthetic compound sourced from chemical synthesis. Its mode of action involves the activation of the immune system through the stimulation of toll-like receptor 7 (TLR7), leading to the induction of various cytokines, such as interferon-alpha, that initiate an antiviral and anti-tumor response.</p>

<p>γ-secretase inhibitor; reduces amyloid-β in brainÂ</p>

<p>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.</p>

<p>Picrotoxin is a GABA-A receptor antagonist that is used to relieve respiratory distress. This drug also is used as an antidote from poisoning by CNS depressants. Picrotoxin works by blocking the GABA activated chloride ionophore.</p>

<p>Ractopamine hydrochloride is a beta-agonist that stimulates the release of fatty acids from adipose tissue, increasing food intake and weight gain in pigs. It has been shown to have significant interactions with other drugs used for bowel disease, as well as with sodium carbonate, which can be used for control analysis. Ractopamine hydrochloride is an effective drug to stimulate the release of estradiol benzoate in rats during pregnancy. The matrix effect observed when analyzing samples containing ractopamine hydrochloride may be due to its ability to bind to serum proteins or lipids. This drug has been shown to have molecular docking properties that are similar to those found in other molecules.</p>

<p>S1RA hydrochloride is a selective antagonist targeting the sigma-1 receptor, which is a type of small molecule ligand. It is synthesized chemically, enabling precise modulation of its properties for experimental use. S1RA functions by selectively inhibiting the sigma-1 receptor, a chaperone protein involved in modulating ion channels and other receptors within the endoplasmic reticulum. This modulation plays a critical role in various cellular processes, including calcium signaling and cellular stress responses.</p>

<p>Used to treat multiple sclerosis; anti-inflammatory</p>

<p>Pantoprazole is a proton pump inhibitor drug that is used to treat erosive esophagitis and promotes healing of tissue damage caused by gastric acid. It is used for the management of GERD. Through the proton pump inhibition, the formation of hydrochloric acid is inhibited thus inhibiting gastric secretion.</p>

<p>Bromocriptine is a dopamine D2 receptor agonist that is used for the treatment of galactorrhoea which is due to hyperprolactinemia and other prolactin-related conditions. This drug is an ergot alkaloid derivative that inhibits prolactin secretion. Additionally, it can be used to management signs and symptoms of Parkinsonian syndrome. Research has indicated this drug for pulmonary fibrosis as well.</p>

<p>Inhibitor of chymotrypsin</p>

<p>Histamine (H2) receptor antagonist</p>

<p>A selective and potent inhibitor of phosphodiesterase 2 (PDE2). Raises cAMP and cGMP levels in neurons, improves social recognition and object memory in murine animals. Reverses anxiolytic effects induced by oxidative stress in mice by blocking cGMP-PKG signaling.</p>

<p>Inhibitor of immunophilin FKBP12 and mTOR signalling with immunosuppressant activity. Zotarolimus inhibits proliferation of endothelial cells and smooth muscle cells and is employed in vascular interventional therapies.</p>

<p>Immune suppressant; prevents pro-inflammatory cytokine release</p>

<p>Hydroxychloroquine is a drug that is used to treat multiple types of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus and discoid lupus. It is a prodrug, which is activated in the liver to hydroxychloroquine. It inhibits the production of inflammatory cytokines and nitric oxide by binding to the toll-like receptor 4 (TLR4) and inhibiting signaling pathways downstream of TLR4 activation. Additionally, Hydroxychloroquine is used to prevent and treat malaria caused by parasitic protozoan from the Plasmodium genus. Furthermore, recent studies revealed that hydroxychloroquine has beneficial effects on COVID-19 patients, as the current evidence shows that hydroxychloroquine inhibits SARS CoV-2 entry in host cells by interfering with endocytosis and affecting the glycoprofile on the spike glycoprotein.</p>

<p>Estrogen receptor degrader; therapeutic use in breast cancer</p>

<p>A potent inhibitor of STING protein (stimulator of interferon genes), a protein that partakes in intracellular DNA sensing pathway.  H 151 blocks palmitoylation of STING, which is required for the formation of multimeric complexes for recruiting downstream signalling molecules. Inhibition of STING by H 151 reduces pro-inflammatory cytokine synthesis.</p>

<p>Rebamipide is a gastroprotective agent that is used to treat various gastrointestinal disorders such as gastric ulcers and GERD. This drug’s mechanism of action is not fully understood however, it is thought to exert its effects by promoting the secretion of protective mucus in the stomach and intestine, which helps to create a barrier against stomach acid and other irritants. Additionally, it has antioxidant and anti-inflammatory properties that can help reduce tissue damage.</p>

<p>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).</p>

<p>Sphingosine-1-phosphate receptor modulator</p>

<p>Thymidylate synthase inhibitor</p>

<p>KBU2046 is an antimicrobial peptide, which is derived from natural or synthetic peptide sequences with potential therapeutic properties. It exerts its effects by disrupting the structure and integrity of bacterial cell membranes through the formation of pores or micelles. This action alters membrane permeability, ultimately leading to cell lysis and death.</p>

<p>Inhibitor of 5-lipoxygenase activating protein_x000D_</p>

<p>Inhibitor of FLT3 and AXL tyrosine kinases</p>

<p>17:0-20:4 Pi (4,5) P2 is a synthetic phosphoinositide, which is a chemically defined lipid derived from laboratory synthesis. It features a specific acyl chain composition with a heptadecanoic acid (17:0) at the sn-1 position and an arachidonic acid (20:4) at the sn-2 position. This phosphoinositide mimics naturally occurring phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), an essential component of cellular membranes.</p>

<p>Inhibits MET, VEGFR1-3, Tie and Ron tyrosine kinases; antineoplastic</p>

<p>Antagonist of nicotinic acetylcholine receptors; nondepolarising muscle relaxant</p>

<p>Dopamine D2 receptor antagonist</p>

<p>N-Acetyl mescaline is a synthetic compound derived from the naturally occurring hallucinogen mescaline, which is sourced from the Peyote cactus (Lophophora williamsii) and other cacti. As an N-acetylated derivative, its chemical modification impacts the compound's mode of action, particularly in its interaction with serotonin (5-HT) receptors.This acetylation can alter the pharmacokinetics, potentially influencing its binding affinity and efficacy at various receptor sites, such as 5-HT2A. This receptor is notably implicated in the mechanism of action of classic psychedelics, mediating their sensory and cognitive effects.While mescaline is known for its strong psychotropic effects, N-Acetyl mescaline presents a modified profile, which may alter its psychoactive properties and duration of action. This compound is primarily studied in research settings to investigate its unique interactions with the neural network and its potential implications for neuroscience.</p>

<p>Selective and potent inhibitor of glucose transporter GLUT1 with IC50 of 2 nM. The compound limits glucose uptake and is able to block basal as well as stress-regulated glycolysis in ovarian cancer cells. It supresses proliferation, viability and tumorigenicity of ovarian cancer cells.</p>

<p>Nicardipine is calcium channel blocker drug that is used for the treatment of hypertension and angina. This drug can also be used in the treatment of asthma and is said to enhance the action of various antineoplastic agents.</p>

<p>SIRT1 activator</p>

<p>Atorvastatin is an HMG-CoA reductase inhibitor which is used to lower lipid levels and to reduce the risk of cardiovascular disease. This drug belongs to the class of medicines called statins. It lowers abnormal levels of cholesterol and lipids to reduce the risk of cardiovascular disease by inhibiting the enzyme HMG-CoA.</p>

<p>Potent and selective inhibitor of polycomb repressive complex 2 (PRC2), by binding to the K27me3-pocket of the regulatory EED subunit. Inhibits H3K27 methylation in histone 3. Has anti-tumor activity in murine xenograft models. Synergistic with EZH2 inhibitor against cancer cell growth.</p>

<p>SHP099 is an allosteric inhibitor of the SHP2 protein, which is derived from targeted small-molecule drug development. Its mode of action involves binding to SHP2 in a region distinct from the catalytic site, thereby stabilizing the protein in its auto-inhibited conformation and preventing activation. This disrupts downstream signaling pathways mediated by SHP2, a protein-tyrosine phosphatase essential in promoting oncogenic signaling through the RAS/MAPK pathway.</p>

<p>Icilin is a transient receptor potential M8 (TRPM8) agonist drug that is used for the treatment of pruritis. This drug has shown to be effective in producing an extreme cold sensation in both human and animal models. It is used in research for studying TRP channels.</p>

<p>Drotaverine is an antispasmodic drug that is used to alleviate gastrointestinal and genitourinary smooth muscle spasms. This drug works by inhibiting phosphodiesterase-4 and increasing levels of cAMP leading to smooth muscle relaxation.</p>

<p>Inhibitor of Rho-kinases</p>

<p>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.</p>

<p>BRK tyrosine kinase (PTK6) inhibitor; anti-proliferative in breast cancer cells</p>

<p>Inhibitor of COX-2 and PDE4 enzymes; NSAID of coxib class</p>

<p>Prilocaine is a drug used as a local anaesthetic in dental procedures. It has been shown to reduce the incidence of pain caused. This drug is also a sodium channel blocker that blocks the influx of sodium into cells.</p>

<p>Amlexanox is an antiallergic and anti-inflammatory drug that has been shown to be effective in treating rhinitis and allergic asthma in clinical studies. It prevents the slow-reacting substance of anaphylaxis (SRS-A) from being released chemically as a mediator and may have antagonistic effects on interleukin-3.</p>

<p>Antagonist of muscarinic acetylcholine receptors</p>

<p>Thalidomide is a piperidinyl isoindole drug that is used to treat various cancers such as myeloma and erythema nodosum leprosum. This drug is immunosuppressive and has anti-angiogenic activity. Thalidomide’s mechanism of action is not fully understood however it is thought to block the activity of tumor necrosis factor-alpha (TNF-α).</p>

<p>This compound is a novel negative allosteric modulator of glutamate metabotropic receptor mGlu7. It is highly selective for mGlu7 over other receptors of mGlu class with IC50 = 795 nM. Although VU 6010608 showed favourable brain penetration in rats, it has been proposed as an in vitro tool for electrophysiology studies. The mGlu7 is broadly distributed within the mammalian central nervous system and it plays a key role in neuronal function and synaptic plasticity.</p>

<p>Inhibitor of isocitrate dehydrogenase 2</p>

<p>Lovastatin is an HMG-CoA reductase inhibitor that is used to lower LDL cholesterol levels and to aid in the management of cardiovascular diseases. Animal studies have demonstrated that this drug has vasculoprotective properties.</p>

<p>NADPH oxidase inhibitor; anti-inflammatory</p>