Ligas Organometálicas

<p>Prostaglandin F2α receptor agonist</p>

<p>5-Fluoro-1-(tetrahydro-2-furyl)uracil is a chemotherapeutic agent, which is a synthetic derivative of uracil. This compound is developed from modified nucleosides with the aim of enhancing antitumor efficacy. Its mechanism of action involves the inhibition of thymidylate synthase, leading to a disruption in DNA synthesis. By integrating into RNA and DNA, it ultimately impedes tumor cell proliferation due to RNA processing interference and DNA damage.</p>

<p>Peptide derived from the endothelial nitric oxide synthase which synthesises nitric oxide in order to protect endothelial cells from vascular diseases, atherosclerosis and thrombosis.</p>

<p>Phosphorylated EGFR peptide substrate.</p>

<p>A glycogen synthase kinase 3β- (GSK3β-) / crosstide fragment representing the phosphorylation site on GSK3β-. GSK3β- is a serine/threonine kinase which regulates glycogen synthase activity and is a key mediator of vertebrate development, tumourigenesis and cell differentiation. GSK3β- is phosphorylated by activated AKT/protein kinase B on serine 9- promoting its inactivation.</p>

<p>Acid α-glucosidase (83-99) (human) is derived from the exogenous enzyme which degrades glycogen, maltose and isomaltose through targeting alpha -1,4 and alpha -1,6 linkages. Once synthesised in its precursor form, within the Golgi it is glycosylated and acquires mannose 6-phosphate residues. This allows it to be transported to the Lysosome in a multistep process.Pompe disease, also known as glycogen storage disease type II, can be diagnosed through the absence of acid α-glucosidase activity within patients. Therefore glycogen degradation in the lysosome is inhibited by this autosomal recessive disorder. This results in the accumulation of glycogen and tissue destruction, hence contributing to the pathologies of muscle weakness and respiratory failure, associated with infantile onset and adult onset Pompe disease.</p>

<p>Idelalisib is a pharmaceutical drug that functions as a PI3Kδ inhibitor, developed through synthetic chemical processes. Its mode of action involves selectively targeting and inhibiting phosphatidylinositol 3-kinase delta (PI3Kδ), a lipid kinase that plays a crucial role in the signaling pathways responsible for cell proliferation, survival, and differentiation. By inhibiting this enzyme, Idelalisib effectively impedes pathways that are often hyperactivated in certain hematologic malignancies, thereby exerting antitumor effects.</p>

<p>Bexarotene is a retinoid and antineoplastic agent that is used for the treatment of solid tumours and t-cell lymphomas. It inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin and research has shown that it induces tumor regression in vivo in some animal models.</p>

<p>Afatinib is a small molecule that inhibits the activity of cellular kinases that are involved in the progression of cancer. It is an Irreversible inhibitor of three members of the ErbB family. This molecule binds covalently to cysteine 797 residue in HER2 and blocks downstream cellular signalling which inhibits cellular growth and promotes apoptosis. It has been researched for the treatment of non-small cell lung cancer (NSCLC), breast cancer, pancreatic cancer and colorectal cancer.</p>

<p>This peptide is phosphorylated by Janus kinase 2 (JAK2) and is an ideal substrate for use in kinase assays. The JAK family of kinases is essential for the signalling of a host of immune modulators in tumour, stromal, and immune cells where they are highly expressed. JAK family proteins mediate the signalling of the interferon (IFN), IL-6, and IL-2 families of cytokines.JAK kinases are associated with cytokine receptors. Cytokine binding to these receptors results in activation of JAK kinases and receptor phosphorylation. Phosphorylated cytokine receptors recruit STAT proteins, which are then phosphorylated by the activated JAK kinases. Phosphorylated STAT proteins form homo- and hetero-dimers that translocate into the nucleus and function as transcription factors.</p>

<p>Carmustine is a DNA alkylating agent which also cross-links DNA. As a result, Carmustine disrupts the function of DNA, resulting in the arrest the cell cycle and apoptosis. Consequently these properties of Carmustine, in addition to its ability to easily transmit through the blood-brain barrier, means it can be used as a cancer treatment, treating cancers such as, breast, ovarian and pancreatic as well as lymphomas and leukemias. Furthermore Carmustine can contribute to cytotoxic effects through its ability to carbamoylate DNA repair enzymes and proteins.</p>

<p>This peptide is phosphorylated by Janus kinase 1 (JAK1) and is an ideal substrate for use in kinase assays. The JAK family of kinases is essential for the signalling of a host of immune modulators in tumour, stromal, and immune cells where they are highly expressed. JAK family proteins mediate the signalling of the interferon (IFN), IL-6, and IL-2 families of cytokines.JAK kinases are associated with cytokine receptors. Cytokine binding to these receptors results in activation of JAK kinases and receptor phosphorylation. Phosphorylated cytokine receptors recruit STAT proteins, which are then phosphorylated by the activated JAK kinases. Phosphorylated STAT proteins form homo- and hetero-dimers that translocate into the nucleus and function as transcription factors.This JAK1 substrate peptide contains an N-terminal glycine-residue.</p>

<p>Antirheumatic; immunosuppressant; neuroprotective; neuroregenerative</p>

<p>A specific inhibitor of Bone Morphogenetic Protein (BMP) type 1 receptors ALK2 and ALK3 (IC50  &lt; 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.</p>

<p>6-OAU is a chemical compound categorized as a cytokinin-like molecule, which is derived from natural plant sources. It functions by modulating gene expression and hormone pathways involved in various plant growth and developmental processes. The mode of action of 6-OAU largely revolves around mimicking the activity of cytokinins, essential plant hormones that regulate cell division, shoot and root growth, as well as delay senescence.</p>

<p>H-FERQHM-OH peptide, corresponding to RNase A 8-13 (Chain A of bovine pancreatic ribonuclease) is a non-amyloidogenic peptide, that can be used as a negative control in amyloid formation experiments together with CRB1001320.</p>

<p>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.</p>

<p>Inhibits actin polymerization</p>

<p>A metabolite of arachidonic acid, synthesised by COX enzymes and prostaglandin E synthases (PGEs). Binds to EP1, EP2, EP3 and EP4 receptors with high affinity (Kd &lt; 10 nM). Therapeutic potential for analgesia, pain relief and arthritic diseases. Enhances differentiation and expansion of iPSC-derived hematopoietic progenitor cells.</p>

<p>Inhibitor of BACE1 protease</p>

<p>rel-(1R,2S)-8-Bromo-1-(3-bromo-4-hydroxy-5-methoxyphenyl)-1,2-dihydro-7-hydroxy-N2,N3-bis[2-(4-hydroxyphenyl)ethyl]-6-methoxy-2,3-naphthalenedicarboxamide is a synthetic chemical compound, which is derived through targeted organic synthesis and structural optimization efforts. Its source lies in advanced laboratory methodologies designed to enhance specific pharmacological properties. The mode of action is expected to involve selective interaction with particular molecular targets, potentially modulating distinct pathways related to cellular function or signaling processes.</p>

<p>Vardenafil is a phosphodiesterase type 5 inhibitor that binds to intracellular targets and competitively inhibits cyclic guanosine monophosphate (cGMP) hydrolysis thus increasing cGMP levels. Vardenafil can be used for the research of erectile dysfunction, hepatitis and diabetes.</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>Inhibitor of TGF-α, CTGF, ERK1/2, NF-κB and FasL; anti-inflammatory</p>

<p>Melatonin is a neurotransmitter produced by the pineal gland that is involved in the regulation of sleep-wake cycles. It can be used to treat several conditions like shift work disorders, insomnia, jet lag, and alterations of the circadian rhythm. Some authors also proposed the use of melatonin against cognitive disorders. In an interesting research conducted on zebrafish, it was found that memory formation occurs better during daytime compared to nighttime, suggesting a role of melatonin in this process. When melatonin was administered during the daytime it caused reduced memory formation. On the contrary, removing the pineal gland or treating the fish with a melatonin antagonist significantly improves nighttime memory formation.</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>Albuterol is a selective beta-2 adrenergic receptor agonist drug that is used to prevent and treat wheezing, shortness of breath, and other breathing difficulties caused by asthma. It relaxes the muscles in the airways, making them more open. Albuterol also has an anti-inflammatory effect.</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>Dual inhibitor of the adaptor protein 2-associated kinase 1 (AAK1) and BMP2-inducible kinase (BMP2K) with IC50 values of 270 nM and 1 μM, respectively. In a recent study, SGC AAK1 1 stabilised β-catenin, inhibited phosphorylation of the AP2 complex subunit mu protein (AP2M1) and activated Wnt signalling in in vitro experiments._x000D_</p>

<p>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.</p>

<p>Selective inhibitor of the platelet derived growth factor receptor PDGFRβ with IC50 value of 4.2 nM. JNJ 10198409 inhibits the PDGFRβ kinase activity and its downstream signalling leading to anti-proliferative and anti-angiogenic effects, which were confirmed in various tumoral cell lines.</p>

<p>Substrate for proline-rich tyrosine kinase 2 (Pyk2)- can be used for substrate phosphorylation assays. Pyk2 is a member of the focal adhesion kinase (FAK) subfamily of cytoplasmic tyrosine kinases. Pyk2 is also known as: calcium-dependent tyrosine kinase (CADTK)- cellular adhesion kinase β- related adhesion focal tyrosine kinase (RAFTK)- or FAK2.Pyk2 functions as a scaffold protein, and it interacts with cytoplasmic proteins at focal adhesion sites to integrate different environmental signals. Pyk2 is activated by several stimuli, including elevated intracellular calcium levels, protein kinase C activation, and exposure to stress factors. Recently, Pyk2 has become a potentially important new therapeutic target or prognostic marker because overexpression of Pyk2 has been found in many human tumours.</p>

<p>HMG-CoA reductase inhibitor</p>

<p>Brimonidine-D-tartrate is a selective alpha-2 adrenergic agonist, which is a pharmacological compound derived synthetically, targeting specific receptor subtypes in the adrenergic receptor family. Its mode of action involves reducing aqueous humor production and increasing uveoscleral outflow in the eye, thereby lowering intraocular pressure. Additionally, it induces peripheral vasoconstriction, playing a role in reducing redness in rosacea.</p>

<p>Dapoxetine is a drug that belongs to the group of selective serotonin reuptake inhibitors (SSRIs). It is used to treat premature ejaculation. This drug inhibits the serotonin transporter allowing for an increased action of serotonin at the postsynaptic cleft, thus promoting ejaculatory delay.</p>

<p>Vipivotide tetraxetan is a radioactive therapeutic agent, which is a radioligand conjugate composed of a DOTA chelator linked to a targeting moiety. The source of this compound lies in its synthesis, where the DOTA ligand is conjugated to a peptide or small molecule that targets specific cell surface antigens expressed on cancer cells.</p>

<p>Ziprasidone is an atypical antipsychotic drug that is used to manage schizophrenia, bipolar mania, and agitation. This drug binds to serotonin and dopamine receptors. As a result it enhances modulation of mood and improves overall cognition.</p>

<p>Inhibitor of stearoyl-CoA desaturase SCD1 with IC50 of 6.3 nM, as measured in the SCD1-expressing human microsomes.  A 939572 exhibited anticancer activity as it reduced cell proliferation and triggered cell killing in human non-small cell lung carcinoma cells. A 939572 inhibited tumour growth in an in vivo model for gastric carcinoma and reduced the oleic acid:stearic acid ratio in mouse liver and plasma.</p>

<p>Ebselen is a non-toxic organoselenium compound with antioxidant, anti-inflammatory and cytoprotective properties. Ebselen is an inhibitor of lipoxygenases, nitric oxide (NO) synthases, protein kinase C, H+/K+-ATPase, thioredoxin reductase and NADPH oxidase. Recently, ebselen has been identified by several studies as a covalent inhibitor of the main protease Mpro from coronaviruses. For the SARS-CoV-2 main protease Mpro, the IC50 value is 0.67 μM and EC50 is 4.57 μM.</p>

<p>Inhibits mTORC1 and mTORC2 serine/threonine kinases</p>

<p>Piracetam analog; AMPA receptor allosteric modulator</p>

<p>During extraction of lecithin from egg yolk, peptide by-products can be isolated and purified by gel filtration. Within the by-products this has led to the discovery of biologically active value-added products. The egg yolk gel filtration (EFGF) fractions were analysed for their antioxidant and angiotensin converting enzyme (ACE) inhibitory activities. EYGF-56 predominantly contained 3 peptides - SDNRNQGY, KGLWE, and IQVPL. KGLWE in EYGF-56 was found to have very strong antioxidant activity. KGLWE showed minimal angiotensin converting enzyme (ACE) inhibitory activity.</p>

<p>Clomipramine is a tricyclic antidepressant drug that inhibits the reuptake of serotonin, norepinephrine, and dopamine. It is used to treat obsessive compulsive disorder, panic disorders and cataplexy. Additionally, Clomipramine is shown to modulate immune activation and shows constant anti-inflammatory properties at therapeutic concentrations by consistently decreasing pro-inflammatory cytokines.</p>

<p>Inhibitor of glucose uptake via GLUT1 and GLUT4 transporters, promoting intracellular glucose deprivation. The compound is a chemical sensitizer to the FAS cell death receptor and is able to break down the resistance of caspase activation. It has potential for anti-cancer therapy as it modulates the Warburg effect in cancer cell lines.</p>

<p>A15 also known as alpha2-Antiplasmin is a serine/protease inhibitor which inactivates plasmin in the blood. To inhibit plasmin in the blood alpha2-Antiplasmin forms a protease serpin complex with plasmin due to interactions of kringle 1 or 3 of plasmin and the lysine residues of alpha2-Antiplasmin's C-terminus. Although synthesised in the Liver A15 is also present within the neurons of the human brain and its expression has been found to be enhanced in Aβ plaques of Alzheimer's disease and during myocardial infarction. A high concentration of alpha2-Antiplasmin in the blood may also contribute to an increased risk of Ischemic strokes. Alternatively its expression appears to be diminished in patients with cirrhosis and acute liver failure. A further function of A15 is its ability to regulate fibrinolysis through crosslinking to fibrin.</p>

<p>Modulator of RBP protein; activator of sphingomyelinase; pro-apoptotic</p>

<p>Prodrug of 5-aminosalicylic acid; anti-inflammatory</p>

<p>Tolvaptan is a vasopressin receptor antagonist. It binds to the V2 receptor in the cytosol and prevents it from activating the aquaporin 2 channel, which regulates water permeability. Inhibition of vasopressin receptors in the kidneys improves fluid and electrolyte balance. Tolvaptan has been shown to be effective for treating congestive heart failure, as well as other disorders that are associated with fluid retention, such as renal dysfunction and metabolic syndrome. Tolvaptan can also be used in combination therapy with other drugs to treat these conditions.</p>

<p>A novel non-covalent inhibitor of the PLpro protease from SARS-CoV-2 and SARS-CoV viruses. GRL 0617 inhibits the proteolytic processing of the viral polypeptide. As PLpro also acts as a protease in pathways involved in innate immunity, there are indications that it can promote immunity against the virus.</p>