Organometallic Ligands

<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>Sotalol is methane sulfonanilide beta adrenergic antagonist drug that is used for the treatment of ventricular arrhythmias and in the management of sinus rhythm in atrial fibrillation. This drug inhibits β-1 adrenoreceptors in the myocardium allowing for a longer sinus node cycle and to slow repolarization.</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>Tretinoin is a type of retinoic acid that can be used for the treatment of acne. It is a chemical inhibitor that binds to nuclear receptors and leads to an increase in apoptosis. This type of retinoic acid helps with cell detachment and increases shedding thus increasing cell turnover. Tretinoin has been shown to have antibacterial efficacy against Staphylococcus aureus, as well as synergistic effects when combined with other agents, such as cyclic lipopeptide antibiotics and quinolones. Additionally, Tretinoin is used in the research and treatment for promyelocytic leukaemia.</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>Amantadine is an antiviral drug that is used to treat dyskinesia in patients with Parkinson’s disease. This drug’s mechanism is not fully understood however it is said to aid in releasing dopamine from the nerve ending in brain cells. Amantadine is also an NDMA antagonist.</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>Long-acting muscarinic antagonist</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>Inhibitor of protein kinase PKC</p>

<p>Adenosine A3 receptor antagonist</p>

<p>Muscarinic antagonist; bronchodilator</p>

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

<p>Inhibitor of LRRK2 kinase</p>

<p>Prodrug of 5-aminosalicylic acid; anti-inflammatory</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>Serotonin uptake inhibitor; anti-depressant</p>

<p>Inhibitor of pan-Raf kinases</p>