Organometallic Ligands

<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>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>VEGFR2 a tyrosine kinase receptor inhibitor; antineoplastic</p>

<p>Increases VEGF via heme oxygenase-1 modulation; anti-ulcer agent</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>RIPK2 protein kinase inhibitor; EGFR inhibitor</p>

<p>Specific inhibitor of glycogen synthase kinase 3 (GSK-3) with IC50 in low nanomolar range. Studies showed that BIO maintains self-renewal in embryonic stem cells (ESCs) as well as increases activity of β-catenin. In neonatal cardiomyocytes, BIO promotes cell cycle by stimulating cell entry into S phase as well as cytokinesis. In germline stem cells from female mice (FGSCs), BIO promoted proliferation and maintenance of FGSCs by activating β-catenin and up-regulating E-cadherin.</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>S26131 is an advanced glycation end product (AGE) inhibitor, which is a synthetic compound designed for laboratory research purposes. It is derived from chemical synthesis processes, offering a robust tool for investigating the biochemical pathways associated with glycation. Its mechanism of action involves the inhibition of AGE formation, which is a post-translational modification resulting from the non-enzymatic reaction between sugars and proteins or lipids. This biochemical modulation is vital for studying the implications of glycation in various physiological and pathological contexts.</p>

<p>Kifunensine is a small molecule inhibitor that was designed and synthesized to inhibit plant and animal α-mannosidase I. It is a potent and specific inhibitor with IC50 in nanomolar range. It inhibits the enzyme isoforms in Golgi apparatus (GMI) and endoplasmatic reticulum (ERMI). The compound prevents mannose trimming on glycoproteins and shifts the glycoform content from complex to oligomannose type. Used for the production of recombinant therapeutic glycoproteins with mannose rich N-linked glycans.</p>

<p>ÎŽ opioid receptor agonist; anti-nociceptive; anti-depressant</p>

<p>Inhibitor of VEGFR, PDGR, c-Kit and Ret; inhibitor of angiogenesis</p>

<p>Positive allosteric modulator of the metabotropic glutamate receptor mGluR5 with EC50 in submicromolar range. The compound is able to increase mGluR5 function in vitro and in vivo. A study showed that ADX-47273 enhanced fear extinction learning as well as improved reversal learning in experimental animals.</p>

<p>Inhibits p38 MAP kinase; anti-inflammatory; neuroprotective</p>

<p>Antagonist of nociceptin receptors</p>

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

<p>3-Hydroxy-5-{[(naphthalen-2-yl)carbamoyl]amino}benzoic acid is a synthetic compound characterized by its complex molecular structure incorporating naphthalene and benzoic acid moieties. As a derivative of benzoic acid, it is typically synthesized through a series of chemical reactions designed to introduce the 3-hydroxy and carbamoyl functional groups, creating a compound with potentially unique bioactive properties.</p>

<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>Potent and selective positive allosteric modulator (PAM) of metabotropic glutamate receptor mGlu4. Valiglurax is orally bioavailable and CNS-penetrant mGlu4 PAM in preclinical development for the Parkinson’s disease therapy and alleviation of the motor symptoms.</p>

<p>Cetirizine is a selective histamine-1 antagonist drug used for the treatment of allergies. One of the common uses is for a condition called allergic rhinitis. As Cetirizine is an antihistamine, its main mode of action is by selectively inhibiting H1 receptors. In vivo and ex vivo animal models have shown insignificant anticholinergic and antiserotonergic effects.</p>

<p>Crizotinib is a drug that belongs to the group of tyrosine kinase inhibitors. It is used in the treatment of cancers, including non-small cell lung cancer, small cell lung cancer, and other types of solid tumours. Crizotinib inhibits the activity of the tyrosine kinase ALK or anaplastic lymphoma kinase, which is involved in many signalling pathways and biological processes. The inhibition of this enzyme leads to decreased energy metabolism, reduced mitochondrial membrane potential and increased susceptibility to apoptosis.</p>

<p>Inhibitor of NLRP3 inflammasome and suppressor of the inflammatory cytokine IL-1β secretion. The compound was tested in diabetic mice and was shown to decrease the incidence of cardiac arrythmias, which are common secondary complications in diabetes mellitus. MCC 950 has potential to reverse diabetes-induced pathologies in cardiac electrophysiology.</p>

<p>Pan-class I phosphatidylinositide 3-kinase (PI3K) inhibitor (IC50 = 3, 33, 3 and 75 nM at catalytic subunits p110α, p110β, p110δ and p110γ respectively). Inhibits proliferation in several cancer cell lines, such as glioblastoma, breast and prostate cancer cells. Has synergistic anti-cancer effect in combination with MEK/ERK kinase inhibitor GDC-0973 (cobimetinib).</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>Inhibits N-Acetyl-mediated interaction between BE2M (E2 conjugating enzyme) and DCN1 (a component of E3 ligase complex). Also has inhibitory action on DCN2 and NEDD8 ubiquitin-like protein. Reduces anchorage-independent growth in DCN1-amplified cell line.</p>

<p>Inhibitor of human neutrophil elastase</p>

<p>Bosentan is a dual endothelin receptor antagonist that is used to treat hypertension. This drug works by blocking the action of endothelin molecules which prevents the narrowing of blood vessels and decreases blood pressure.</p>

<p>Potent inhibitor of γ-secretase. LY 411575 inhibited production of amyloid β (Aβ) peptides with IC50 of 0.078 nM in vitro as well as decreased levels of Aβ40 and Aβ42 amyloids in brain of a mouse model for Alzheimer’s disease. In vitro studies confirmed that LY 411575 inhibited cleavage of Notch receptor at S3 site with IC50 of 0.39 nM, which blocked Notch activation and downstream signalling, leading to apoptosis in primary and immortalized Kaposi's sarcoma cells.</p>

<p>Regaloside D is a natural product derived from plant sources, specifically isolated from certain species known for their bioactive properties. It functions as a glycoside, a compound in which a sugar is bound to a non-carbohydrate moiety, potentially influencing a variety of cellular processes through its interaction with specific molecular targets.</p>

<p>Benazepril is a nonsteroidal anti-inflammatory drug that can be used to treat hypertension, heart failure and renal failure. It is an angiotensin-converting enzyme (ACE) inhibitor that blocks the conversion of angiotensin I to angiotensin II. This inhibition prevents the vasoconstrictive effects of this peptide, which are mediated through activation of the renin-angiotensin system.</p>

<p>Inhibitor of leucine-rich repeat kinase LRRK2Â</p>

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

<p>Azumolene is a muscle relaxant drug, which is a synthetic derivative of dantrolene originating from hydantoin. The mode of action of Azumolene involves the inhibition of calcium ion release from the sarcoplasmic reticulum of skeletal muscle fibers. By impeding this release, Azumolene effectively reduces muscle contraction, thereby acting as a potent muscle relaxant.</p>

<p>Mianserin is a tetracyclic antidepressant drug that has antihistaminic and hypnosedative properties. It is used to treat depression in adults and children, as well as other disorders such as chronic pain and irritable bowel syndrome. This drug’s mechanism of action is not fully understood but is said to block alpha-adrenergic, histamine H1 and serotonin receptors.</p>

<p>Methotrexate is a chemotherapeutic and immunosuppressive medication, which is a synthetic analog of folic acid. Its source is through chemical synthesis, mimicking the structure of dihydrofolate in order to exert its effects. Methotrexate acts primarily by inhibiting the enzyme dihydrofolate reductase (DHFR), leading to a decrease in tetrahydrofolate production. This disruption in folate metabolism results in the inhibition of DNA, RNA, and protein synthesis, which affects rapidly dividing cells.Methotrexate is employed broadly in clinical oncology as an antineoplastic agent, particularly in the treatment of leukemias, lymphomas, breast cancer, and osteosarcoma. Additionally, it serves as a cornerstone for managing autoimmune diseases such as rheumatoid arthritis and psoriasis, where it helps modulate the aberrant immune response. The dual role of Methotrexate in oncology and immunosuppression underscores its versatility and critical importance in therapeutic regimens. However, its use demands careful monitoring due to potential adverse effects on non-cancerous cells and organ systems, necessitating precise dosage management and patient evaluation.</p>

<p>Inhibits actin polymerization</p>

<p>Specific inhibitor of the ubiquitin specific protease-7 (USP7), which is a validated deubiquitinase of the E3 ubiquitin-protein ligase MDM2. The compound inhibits the USP7 deubiquitinase activity by binding to acidic amino acid residues important for the interaction with ubiquitin. Induces tumor cell death and enhances cytotoxicity of chemotherapeutic agents.</p>

<p>Vanilloid receptor 1 antagonist</p>

<p>Inhibitor of p38 kinase</p>

<p>A potent inhibitor of phosphodiesterase type 9 (PDE9) tested in human and murine in vitro assays (IC50 values: 55 nM and 100 nM respectively). BAY 73-6691 induces long-term potentiation and improves memory in rodents. Has therapeutic potential for Alzheimer’s disease.</p>

<p>Short acting monoamine oxidase inhibitor</p>

<p>AZD9567 is a selective glucocorticoid receptor modulator (SGRM), which is a synthetic pharmaceutical compound. Its source is rooted in medicinal chemistry efforts to design ligands that selectively interact with glucocorticoid receptors. The mode of action of AZD9567 involves binding to glucocorticoid receptors with high specificity, modulating their activity to trigger anti-inflammatory and immunomodulatory responses while minimizing common side effects associated with traditional glucocorticoids.</p>

<p>Loratadine is a non-sedating, inverse agonist antihistamine used for the treatment of allergic rhinitis, an IgE (immunoglobulin E) mediated disease. Loratadine binds to histamine H1 receptors, preventing histamine from binding and causing an allergic reaction.It has been found to inhibit the release of eosinophil cationic protein by acting on different components of allergic inflammation, in particular in the modulation of ICAM-1 expression on nasal epithelial cells as a mechanism of protective for the epithelium, and therefore, the damage of mucosa is reduced. In recent studies, it was found that loratadine is a potent HR1 antagonist with in vitro inhbitory effect on human mast-cell lines, HMC-1 (from mast cell leukaemia) with an IC50 between 10 and 50 μM.Loratadine is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready to use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>Malotilate is a pharmacological agent that is used to treat symptoms of hepatitis, bowel disease, and collagen diseases. This drug reduces collagen synthesis and cell migration activity of fibroblasts in vitro. It also has been shown to facilitate liver regeneration in rats.</p>

<p>Opioid receptor antagonist</p>

<p>Analeptic</p>

<p>(S)-Mephenytoin is a substrate of cytochrome P450 enzyme CYP2C19 (a hydroxylase). It is an effective anticonvulsant that improves control of seizures in patients. According to studies, the drug exhibits a genetic polymorphism in CYP2C19 that results in reduced metabolism in some individuals.</p>

<p>(2R)-Arimoclomol maleate is an investigational pharmaceutical compound, which is an orally bioavailable small molecule with pharmacological activity primarily targeting cellular protein homeostasis mechanisms. This therapeutic agent is derived from molecular chaperones and operates by selectively enhancing the expression of heat shock proteins (HSPs). The mechanism of action involves the modulation of the heat shock response, wherein (2R)-Arimoclomol maleate amplifies the natural cellular defense pathways against protein misfolding and aggregation.</p>

<p>Angiotensin II receptor antagonist</p>

<p>Inhibitor of PDE4 enzyme; anti-inflammatory</p>