Organometallic Ligands

<p>ABTL-0812 is an investigational anticancer compound, which is a synthetic small molecule with a novel mechanism of action. It is derived from the research efforts focused on targeting key metabolic pathways in cancer cells. The mode of action of ABTL-0812 involves the modulation of the Akt/mTOR pathway, leading to the induction of autophagy-mediated cell death, a process that is selectively cytotoxic to cancer cells.</p>

<p>Inhibitor of ERK1 and ERK2 serine/threonine kinases</p>

<p>Prostaglandin F2α receptor agonist</p>

<p>Orally available and central nervous system-penetrant inhibitor of GlyT1 glycine transporter SLC6A9. PF 03463275 was shown to enhance neuroplasticity and cognitive remediation in schizophrenia patients. In animal studies, PF 03463275 also influenced retina as changes in electroretinogram were detected in albino rats.</p>

<p>Inhibitor of glycogen phosphorylase and alpha-glucosidases</p>

<p>Apraclonidine is an alpha adrenoreceptor agonist that is used in the treatment of raised intraocular pressure. This drug’s mechanism of action is not fully understood however, animal and human studies suggested that Apraclonidine reduces aqueous humor production and increases uveoscleral outflow.</p>

<p>A calcium-binding protein S100A9 inhibitor with immunomodulatory activity that reduces pathology in experimental collagenase-induced osteoarthritis.</p>

<p>TP-434 2HCl is a hydrochloride salt form of a novel synthetic compound. It is synthesized through a complex organic chemical process, exploiting cutting-edge methodologies to ensure high purity and effectiveness. The compound acts primarily by inhibiting specific bacterial enzymes critical to bacterial replication and survival, thereby exhibiting potent antimicrobial properties.</p>

<p>Selective inhibitor of the interaction between the UNC119 chaperone and its cargo. Squarunkin A inhibits activation of Src kinase by interrupting the interaction between the myristoylated peptide at the N-terminus of the Src kinase and UNC119A chaperone (IC50 = 10 nM). Squarunkin A impairs the UNC119-mediated enrichment of plasma membrane with non-receptor protein tyrosine kinase Src, resulting in the decrease in Src autophosphorylation and decreased oncogenic Src signalling.</p>

<p>Enzastaurin is a synthetic small molecule inhibitor, which is derived from chemical synthesis with a primary mode of action as an inhibitor of protein kinase C beta (PKCβ). As a potent pathway modulator, it disrupts signal transduction pathways involved in cell proliferation and survival. The inhibition of PKCβ is particularly important as this enzyme is linked to the progression and survival of certain cancer types. Through this mechanism, Enzastaurin impedes the downstream activities that promote tumor growth and angiogenesis.</p>

<p>Acipimox is a niacin derivative that is used as a hypolipidemic agent. Acipimox prevents the liver from producing triglycerides and from secreting VLDL, which indirectly results in a slight decrease in LDL and an increase in HDL. Also, it stimulates leptin release and improves insulin sensitivity.</p>

<p>Flupirtine is a pyridine derivative that is used as a non-opioid analgesic. Flupirtine promotes Bcl-2, raises glutathione levels, activates an inward rectifying potassium channel, and reverses the effect of calcium on neuronal cell death by inhibiting its release from intracellular stores. Although it doesn't attach to the receptor, flupirtine functions as an NMDA receptor antagonist. It is used for the treatment of fibromyalgia.</p>

<p>Nitrogen mustard derivative; DNA crosslinking agent; anti-cancer agent</p>

<p>Activator of RET signalling cascade and a derivative of a GFL mimetic compound BT 13. Molecular docking calculations and molecular dynamics simulations were performed in GDNF−GFRα1−RetA complex and showed that BT 18 binds to the allosteric site in GFRα1 as well as RetA surface interfacing GFRα1.</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>Modulator of S1P receptor</p>

<p>Agonist of H3 and H4 receptors</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>Moracin C is a prenylated flavonoid, which is a type of naturally occurring compound. It is derived from the Morus genus, commonly known as mulberry trees. This compound functions primarily as an antioxidant, showing activity that may protect cells from oxidative stress by neutralizing free radicals.</p>

<p>Cladribine is a purine nucleoside analogue that interferes with DNA synthesis by acting as a false building block in the DNA chain during replication. Cladribine is incorporated into the growing DNA chain, causing chain termination and leading to DNA damage, apoptosis (programmed cell death), and ultimately cell death. Cladribine is structurally similar to adenosine, but is partially resistant to breakdown by adenosine deaminase due to a chlorine molecule at position 2. This causes it to accumulate in cells and interfere with the targeted cell's ability to process DNA. This mechanism of action makes cladribine an effective treatment for certain types of cancer and autoimmune diseases, where it targets rapidly dividing cells.</p>

<p>LW-II-41-27 is a novel Eph receptor tyrosine kinase inhibitor used for cancer treatment.</p>

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

<p>Bremelanotide acetate is a synthetic peptide therapeutic, which is derived from the melanocortin receptor agonist class. Its primary source involves chemical synthesis designed to mimic endogenous hormone analogs that target specific receptors in the body. The mode of action of bremelanotide acetate involves activating melanocortin receptors, particularly the MC4 receptor in the central nervous system. This activation leads to modulation of brain pathways involved in sexual arousal and desire.</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>A small molecule inhibitor of polycomb complex protein BMI-1, a gene often overexpressed in tumors and therefore a popular therapeutic target in cancer. Anti-tumor effects of PTC 209 have been demonstrated in colorectal carcinoma, acute myeloid leukemia, multiple myeloma and head neck squamous cell carcinoma. As a regulator of self-renewal, inhibition of BMI-1 by PTC 209 also reduces growth of colorectal cancer initiating cells.</p>

<p>Specific inhibitor of the phosphoinositide 3-kinase (PI3K) alpha subunit with IC50 of 32 nM. In heart muscle it negatively regulates hypertrophic growth, causes increase in late sodium current and leads to arrhythmias. In tumours it inhibits the p110α subunit of PI3K and blocks growth factor signalling resulting in reduced tumour growth.</p>

<p>Maprotiline is a tetracyclic antidepressant that is used for the treatment of major depressive disorder and anxiety that is associated with depression. This drug inhibits noradrenaline reuptake and has anticholinergic properties. Additionally, Maprotiline inhibits the amine transporter which allows for a delay in the reuptake of noradrenaline.</p>

<p>Inhibitor of COX-1 and COX-2 cyclooxygenases</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>Lapatinib is an antineoplastic agent used to treat breast and lung cancer. This drug is also a tyrosine kinase inhibitor and inhibits human epidermal growth factor receptor type 2 (HER2/ERBB2) and epidermal growth factor receptor (HER1/EGFR/ERBB1). Lapatinib has shown to inhibit ERBB-driven tumor cell growth in vitro and in various animal models.</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>Inhibitor of HIF prolyl hydroxylase</p>

<p>Adenosine-A1 receptor agonist</p>

<p>MAP kinase kinase (MEK) inhibitor. Binds to MEK-1, preventing phosphorylation and activation by Raf or MEK kinase. PD 098059 enhances self-renewal in stem cells. Has anti-growth and anti-proliferative effects on AML cells. Anti-apoptotic effect on AML cells observed in synergy with Nutlin-3a.</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>Ticagrelor is a P2Y12 receptor antagonist that has been shown to reduce the risk of myocardial infarction. It inhibits the formation of thromboses. Ticagrelor binds to the adenosine diphosphate (ADP) site on the platelet P2Y receptor and prevents ADP from activating this receptor. It is used for the prevention of myocardial infarctions, strokes and cardiovascular disease.</p>

<p>Inhibits actin polymerization</p>

<p>Gonadotropin-releasing hormone agonist</p>

<p>Inhibitor of dihydroorotate dehydrogenase; anti-inflammatory; immunomodulatory</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>Inhibitor of CK2 protein kinase; anti-proliferative</p>

<p>A potent, reversible and slow-binding inhibitor of delta-5 desaturases (D5Ds), by binding to the desaturase domain. Inhibiting D5D has therapeutic applications in inflammatory diseases. This is due to the increase in anti-inflammatory DGLA-derived eicosanoids and decrease in pro-inflammatory AA-derived eicosanoids.</p>

<p>17:0-20:4 Pi(5)P is a synthetic phosphoinositide, which is a specialized type of lipid molecule derived from inositol. Phosphoinositides are critical components of cell membranes and are involved in various cellular processes. The source of this molecule is a combination of chemically synthesized fatty acyl chains and inositol phosphates. Its mode of action involves acting as a substrate or modulator within phosphoinositide signaling pathways, which are crucial for cellular communication and membrane trafficking.</p>

<p>BI-0115 is a highly selective inhibitor for the lectin-like oxidised low-density lipoproteins (LDL) receptor 1 (LOX-1). In vitro, BI-0115 inhibits internalisation of oxidised LDL (oxLDL) with IC50 of 5.4?µM. The crystal studies revealed that BI-0115 glues two LOX-1 dimers together, resulting in blocked access of oxLDL. LOX-1 is a Ctype lectin-like receptor expressed on endothelial cells, macrophages and vascular smooth muscle. It is responsible for the regulation, internalisation and degradation of oxidised low-density lipoproteins (oxLDL). BI-0115 is a novel inhibitor to LOX-1 and is a valuable tool to study LOX-1 biology, and their role in diseases, such as, cancer and atheroschelerosis.</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>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>Probenecid is a uricosuric agent that is used to treat gout and hyperuricemia. This drug works by inhibiting the reabsorption of uric acid in the renal tubes which results in more uric acid being passed out in the urine. By lowering uric acid levels, Probenecid helps prevent the formation of uric acid crystals in joints, reducing the risk of gout attacks. This drug can also be used as an adjunct to antibacterial therapy.</p>