Ligands organométalliques

<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>Specific inhibitor of the mitochondrial pyruvate carrier complexes MPC1 and MPC2. The compound blocks the pyruvate transport across the inner mitochondrial membrane and therefore reduces pyruvate influx into the gluconeogenesis. It supresses glucose production in hepatocytes and was proposed for the control of hyperglycaemia in diabetic patients. Also used for the sensitisation of cancer cell lines to chemotherapy.</p>

<p>Prostaglandin F2α receptor agonist</p>

<p>Activator of SIRT1 deacetylase</p>

<p>Inhibitor of cyclin dependend kinases</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>Antagonist of H1 histamine receptors</p>

<p>Mineralocorticoid (aldosterone) receptor antagonist</p>

<p>Inhibitor of cathepsins and other cysteine proteases</p>

<p>17:0-20:4 PI (3,4,5) P3 is a synthetic phosphoinositide, a type of lipid molecule, which is typically derived from chemical synthesis using specialized lipid chemistry techniques. This product is designed to mimic natural phosphoinositides found within the cellular membranes. Its mode of action involves acting as a substrate for studying kinase activities and phosphatase interactions within signaling pathways. 17:0-20:4 PI (3,4,5) P3 plays a critical role in cellular signaling by serving as a docking site for signaling proteins with specific lipid-binding domains, influencing downstream signaling pathways.</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>Docetaxel is a cytotoxic semi-synthetic taxane and is an anthracycline antibiotic. The compound is an anti-microtubule agent and has significant inhibitory activity in solid tumors either alone or in combination with other chemotherapeutic agents.<br>Docetaxel trihydrate 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>Amitryptylline is a tricyclic antidepressant that is used to treat depression and to relieve depression associated anxiety. Although its mechanism is not fully understood, it is suggested that this drug inhibits norepinephrine and serotonin thus increasing their concentrations at the synaptic clefts. Additionally, Amitryptylline has shown to have anticholinergic properties.</p>

<p>EGFR tyrosine kinase inhibitor</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>Naltrexone is a derivate of noroxymorphone and is a narcotic antagonist used for the treatment of opioid overdose. This drug is a pure opioid antagonist and blocks the effects of endogenous opioids.</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>

Inhibitor of COX-1 and COX-2 cyclooxygenases

<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>BIA 10-2474 is an investigational pharmaceutical compound that functions as a fatty acid amide hydrolase (FAAH) inhibitor. This compound is derived from synthetic sources and works by inhibiting the FAAH enzyme, which is responsible for the degradation of endocannabinoids such as anandamide in the central nervous system. By inhibiting FAAH, BIA 10-2474 increases the levels of endocannabinoids, potentially impacting pain, mood, and neuroinflammation pathways.</p>

<p>Inhibitor of aurora kinases</p>

<p>Long-acting muscarinic antagonist</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>Inhibitor of protein kinase PKC</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>Tucatinib is a small molecule, tyrosine kinase inhibitor, which is a synthetic, targeted therapeutic agent with a specific mode of action. It specifically inhibits the kinase activity of the human epidermal growth factor receptor 2 (HER2), a member of the epidermal growth factor receptor (EGFR) family. HER2 is overexpressed in a significant subset of breast cancers, leading to aggressive tumor characteristics and poor prognosis.</p>

<p>Sunitinib is a receptor tyrosine kinase inhibitor and a chemotherapeutic agent used for the treatment of renal cell carcinoma. This drug can also be used to treat gastrointestinal tumors that are resistant to imatinib. Sunitinib inhibits VEGFR1, VEGFR2, VEGFR3, PDGFR and KIT tyrosine kinases.</p>

<p>Synthetic analog of vasopressin; anti-diuretic; hemostatic</p>

<p>Timolol is an ophthalmic beta-adrenergic blocker that is used to lower the intraocular pressure in patients with glaucoma. It is also used to treat hypertension, as well as other conditions, such as arrhythmias, thyrotoxicosis and angina pectoris. The drug acts by blocking β1-receptors on the surface of heart muscle cells and blood vessels, thereby reducing the workload on the heart and lowering blood pressure.</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>Dexrazoxane is a cytoprotective drug that is used in chemotherapy to provide cardio-protection against anthracycline toxicity. It is an antimitotic agent with immunosuppressive properties. Dexrazoxane works by binding to iron in the cell, preventing it from being released. Dexrazoxane is also a catalytic inhibitor of topoisomerase II.</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>A non-peptide antagonist of orexin receptors, selective for subtype OX1 over OX2 (50-fold more). Systemic administration in vivo inhibits orexin-A induced grooming and feeding. Elicits sedative and anorectic effects in vivo. Reduces intake of food in rats, induced by orexin-A or overnight fasting.</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>Rigosertib sodium is an experimental chemotherapeutic agent that is a derivative of benzyl styryl sulfone. It is synthesized chemically and functions primarily by inhibiting key signaling pathways involved in cancer cell proliferation. Specifically, Rigosertib targets the RAS signaling pathway along with the phosphatidylinositol-3-kinase/AKT and polo-like kinase 1 (Plk1) pathways, impeding the progression of the cell cycle and inducing apoptosis in malignant cells.</p>

<p>Dofetilide belongs to the class of antiarrhythmic agents. It is a class III antiarrhythmic agent, which acts by blocking the potassium ion channels in the heart. It is used for the management of normal sinus rhythm and in atrial fibrillation. In vitro studies have shown that Dofetilide can prevent arrhythmias resulting from experimental models of congestive heart failure and can prevent re-entry mechanisms that lead to tachycardia.</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>Vildagliptin is an antihyperglycemic agent that is used for the management of type 2 diabetes mellitus. This drug is a dipeptidyl peptidase 4 inhibitor and prevents the degradation of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This leads to improved glycemic control.</p>

<p>mGluR5 antagonist</p>

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

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

<p>Pidotimod is a small molecule (dipeptide) that acts as immunomodulator. It activates the immune system by binding to Toll-like receptor (TLR) 4 and TLR2 and it is involved in the regulation of TLRs signaling pathways. Pidotimod has chemokine activity on CXC chemokine receptor 3 (CXCR3) that triggers monocyte adhesion and migration by activation of tyrosine phosphorylation-based cell signaling. Recent studies showed that pidotimod can be used to treat acute respiratory tract infections (RTIs) and its pharmacokinetic studies has shown its ability to boost the immunoresponse and favouring the increase in the level of immunoglobulins (IgA, IgM, IgG) and T-lymphocytes (CD3+, CD4+). Pidotimod also exhibits anti-inflammatory properties by inhibiting the production of pro-inflammatory molecules such as IL-6 and TNF-α, which are linked to autoimmune diseases.</p>

<p>MK 886 is a leukotriene antagonist that has been studied for use in treating atherosclerosis. This drug inhibits the 5-lipoxygenase activating protein thus inhibiting 5-lipoxygenase.</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>Synthetic estradiol derivative</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>Sulindac is a non-steroidal anti-inflammatory drug that has anti-inflammatory and analgesic properties. It is used to relieve the pain of osteoarthritis and rheumatoid arthritis by reducing inflammation and inhibiting the production of prostaglandins, which are chemicals that cause inflammation.</p>

<p>Selective inhibitor of the Src kinase family with subnanomolar IC50 values and good selectivity over c-Abl, PDGFRα and c-Kit kinases. The compound is effective in inhibiting growth in drug resistant cancer cell lines. In a recent study, it inhibited the growth of HER2-positive breast cancer cell lines which were resistant to pan-HER family kinase inhibitors such as lapatinib.</p>

<p>RET receptor tyroine kinase inhibitor</p>

<p>β3-adrenoceptor agonist</p>

<p>Potent inhibitor of the interaction between defective cullin neddylation protein DCN1 and NEDD8-conjugating enzyme UBC12 with IC50 of 11 nM. WS 383 blocks the DCN1-UBC12 interaction in a reversible manner, selectively inhibits Cul3/1 neddylation and induces accumulation of p21, p27, and NRF2 proteins.</p>

<p>Inhibitor of cyclin-dependent kinases CDK4 and CDK6</p>

<p>Irbp (1-20) is a synthetic peptide fragment derived from the interphotoreceptor retinoid-binding protein (IRBP). This product originates from a segment of IRBP, a vital protein found in the interphotoreceptor matrix of the eye. IRBP plays a crucial role in the transport of retinoids between the photoreceptors and retinal pigment epithelium, essential for the visual cycle.</p>

<p>Inhibitor of transcriptional coactivator PGC-1a; anti-diabetic agent</p>

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

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

<p>Inhibitor of carbonic anhydrase; muscle relaxant</p>

<p>Inhibits VEGFR1, VEGFR2, VEGFR3, c-kit and PDGFR tyrosine kinases</p>

<p>Antagonist of muscarinic (M3) receptor</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>A potent ATP-competitive inhibitor of tropomyosin-related kinases (TRK1, TRK2 and TRK3), members of the receptor tyrosine kinase family of neurotrophin receptors. Tumors with oncogenic TRK fusions are sensitive to larotrectinib, leading to reduced proliferation and tumor growth in patients with soft tissue sarcoma, triple-negative breast cancer and lung cancer.</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>Full antagonist to the estrogen beta receptor (ERβ) with 36-fold selectivity for the β over α receptor. ERβ is a tumour suppressor and PHTPP is a useful tool to study the biology of estrogen-dependent tumours.</p>