Organometallic Ligands

<p>Nilutamide is an antineoplastic agent that is used to treat prostate cancer. This drug is an androgen receptor antagonist and binds with androgen receptors thus blocking its action and resulting in growth arrest.</p>

<p>Soyasaponin II is a naturally occurring triterpenoid saponin that is primarily extracted from soybeans, a rich source of biologically active phytochemicals. Its mode of action involves the modulation of cellular pathways and the alteration of membrane dynamics, which can affect various signaling cascades. This compound is particularly noted for its potential anti-inflammatory, antioxidant, and anticancer properties, making it a subject of extensive research in pharmacological contexts.</p>

<p>Fluvastatin is a statin that lowers blood cholesterol and triglycerides by inhibiting HMG-CoA reductase, an enzyme that plays a critical role in the synthesis of cholesterol. Fluvastatin has also been shown to reduce the incidence of myocardial infarction, and to reduce atherosclerotic lesions in animal models, reducing the incidence of cardiovascular disease. Fluvastatin also has been shown to inhibit the activation of toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS), which may be related to its anti-inflammatory effects. Furthermore, through lowering blood cholesterol, Fluvastatin also inhibits tubulointerstitial injury and prevents renal damage caused by high concentrations of the lipid.</p>

<p>BRAF kinase inhibitor; antineoplastic</p>

<p>Apixaban is an anticoagulant agent used for the prophylaxis of stroke and deep vein thrombosis leading to pulmonary embolism. This drug is an inhibitor of factor Xa and prothrominase. As a result, this prevents the formation of a thrombus.</p>

<p>A potent antagonist of androgen receptor with IC50 value of 16 nM. Binds androgen receptors, thereby inhibiting nuclear translocation, DNA binding and transcriptional activation. Has therapeutic applications in non-metastatic, castration-resistant prostate cancer.</p>

<p>Rosuvastatin is a drug that belongs to the group of statins. It is used for the treatment of high cholesterol and as an adjunct therapy for patients with coronary heart disease. Rosuvastatin reduces serum cholesterol by inhibiting HMG-CoA reductase, which is the rate-limiting enzyme in the production of cholesterol. Furthermore, this drug has been shown to have anti-inflammatory properties, which may be due to its ability to inhibit prostaglandin synthesis.</p>

<p>GC 376 is an inhibitor of the main protease Mpro (3CLpro) in coronaviruses as well as picornaviruses. This broad-spectrum antiviral compound has been used as investigational veterinary drug for treatment of feline infectious peritonitis virus (FIPV) infections. Recent studies also showed that GC 376 inhibits the main protease Mpro (3CLpro) from SARS-CoV-2 with IC50 of 0.03 μM and EC50 of 3.37 μM.</p>

<p>Required for blood coagulation</p>

<p>Polmacoxib is a non-steroidal anti-inflammatory drug (NSAID), which is derived through synthetic chemical processes. It functions as a selective cyclooxygenase-2 (COX-2) inhibitor. By selectively inhibiting the COX-2 enzyme, polmacoxib reduces the conversion of arachidonic acid to prostaglandins that mediate inflammation and pain, while sparing the COX-1 enzyme that protects gastric mucosa and maintains platelet function.</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>Tricyclic antidepressant</p>

<p>Histone acetyltransferase inhibitor of p300/CBP; anti-proliferative</p>

<p>6-O-Feruloylglucose is a bioactive compound, which is a glycosylated derivative of ferulic acid. It is derived from plant sources, particularly being prevalent in the cell walls of cereals and other plant materials. The compound's mode of action is associated with its ability to act as an antioxidant, neutralizing free radicals by donating hydrogen atoms or quenching reactive oxygen species. This makes it a significant molecule in the potential prevention of oxidative stress-related conditions.</p>

<p>Hydroxyl radical scavenger; anti-vasospastic</p>

<p>Budesonide is a glucocorticoid receptor drug that is used to treat inflammatory diseases of the lungs such as COPD, Crohn’s disease and asthma. This drug promotes anti-inflammatory genes such as interleukin-10. Budesonide aims to reduce inflammation in patients suffering from respiratory disease.</p>

<p>Enalapril is a long-acting angiotensin-converting enzyme inhibitor. It is used to treat hypertension and congestive heart failure, as well as chronic cough due to postnasal drip or bronchitis. Enalapril is an active inhibitor of the synthesis of angiotensin II and other vasoconstrictor substances that are involved in the regulation of blood pressure. It binds reversibly to the active site on angiotensin-converting enzyme (ACE) and blocks its activity by forming strong hydrogen bonds with residues on ACE, thereby preventing it from converting angiotensin I into angiotensin II. This leads to a significant reduction in blood pressure.</p>

<p>Fibroblast growth factor receptor inhibitor</p>

<p>As a synthetic trifluorinated glucocorticoid receptor agonist, Fluticasone exhibits anti-inflammatory properties. When binding to and activating glucocorticoid receptors, Fluticasone initiates the activation of lipocortin which inhibits cytosolic phospholipase A2. Consequently, the cascade of inflammatory mediator synthesis reactions are inactivated and the production of inflammatory cells namely mast cells, dendritic cells, macrophages and eosinophils and the cytokines that they produce are greatly reduced.It is this anti-inflammatory role which has enabled Fluticasone to successfully treat conditions such as asthma, emphysema, allergic rhinitis and atopic dermatitis. It has also been seen to increase anti-inflammatory effects of annexoin-1 and mitogen-activated kinase phosphatase-1; reduce mucus gland secretions and increase the number of beta-2 receptors on smooth muscles of the airways.<br>Fluticasone 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>Pramipexole is a non-ergot dopamine agonist that is used for the treatment for the signs and symptoms of Parkinson’s disease and restless leg syndrome. The exact mechanism for this drug is unknown, however it is thought to cause stimulation of the dopamine receptors in the striatum of the brain.</p>

<p>Verapamil is drug that belongs to the class of drugs known as calcium channel blockers. It is used to treat high blood pressure, angina and other cardiovascular disorders. It works by relaxing the blood vessels so that blood can flow more easily. It does this by inhibiting the calcium ion influx through slow channels into conductile, contractile myocardial cells and vascular smooth muscle cells.</p>

<p>Ibandronate is a bisphosphate used in the treatment of osteoporosis in postmenopausal women. This drug slows down the activity of osteoclasts resulting in a slower process of bone breakdown. This drug also inhibits farnesyl diphosphate and induces apoptosis of hematopoietic tumor cells.</p>

<p>Bestatin is a competitive protease inhibitor. It inhibits aminopeptidase N and is being studied for the use and treatment for acute myelocytic leukemia.</p>

<p>Ticlopidine is a platelet aggregation inhibitor that is used in the prevention of conditions associated with thrombi such as stroke and ischemic attacks. This drug blocks the ADP receptor that is involved in GPIIb/IIIa receptor activation leading to platelet aggregation. By reducing platelet aggregation, ticlopidine helps prevent the formation of harmful blood clots that could block blood flow in arteries.</p>

<p>Sarpogrelate is a serotonin antagonist drug that is used for the treatment of various diseases such as diabetes, coronary artery disease and atherosclerosis. This drug inhibits serotonin-induced platelet aggregation.</p>

<p>A selective VHL inhibitor that stabilizes the hydroxylated form of HIF-α, resulting in upregulation of downstream target genes and proteins. Provides a tool for studying hypoxic signaling pathway.</p>

<p>Benserazide is a drug that is used for the treatment of Parkinson’s disease and restless leg syndrome. This drug is a decarboxylase inhibitor and is usually used in combination with Levodopa.</p>

<p>Lercanidipine is a calcium channel blocker that is used for the treatment of hypertension. This drug inhibits ion channels and interferes with the release of calcium from the sarcoplasmic reticulum. As a result, coronary and systemic arteries are dilated, allowing for an increased supply of oxygen to myocardial tissue. .</p>

<p>Flunarizine is calcium channel blocker that helps to reduce muscle spasms. It shows antimigraine and anticonvulsive activity. This occurs by inhibiting the influx of extracellular calcium through myocardial and vascular membrane pores by physically inhibiting the voltage-dependent calcium channels. Additionally, this drug is a D2 dopamine receptor antagonist.</p>

<p>Dutasteride is an androgenic compound and a 5α-reductase inhibitor that is used to treat benign prostatic hyperplasia (BPH) and male pattern baldness. Dutasteride reduces prostate volume and improves symptoms of BPH by inhibiting the enzyme 5α-reductase, which converts testosterone to dihydrotestosterone.</p>

<p>Dapoxetine is a serotonin reuptake inhibitor drug that is used to treat premature ejaculation. This drug works by increasing the levels of serotonin in the brain, which in turn can help to delay the reflex that triggers ejaculation. As a result, it delays ejaculation and improves control over this.</p>

<p>Tizanidine is an alpha-2 adrenergic agonist drug that is used in the treatment of muscle spasticity. This drug binds to alpha-2 adrenergic receptors and causes presynaptic inhibition of motor neurons. Additionally, it leads to a reduction in the release of amino acids such as glutamate and aspartate which have an excitatory effect.</p>

<p>Diclofenac is a non-steroidal anti-inflammatory drug that is used to treat the signs and symptoms of arthritis and osteoarthritis. This drug inhibits COX-1 and COX-2 enzymes. As a result, it reduces pain and inflammation in joints. Diclofenac is usually used as a first line therapy for acute and chronic pain.</p>

<p>Pan-EGFR inhibitor (HER1, HER2 and HER4); antineoplastic</p>

<p>Procarbazine is an alkylating agent used in chemotherapy to treat brain cancer and Hodgkin's lymphoma. It methylates guanine in DNA which causes the strands to become prone to breakage, thus inhibiting both DNA and RNA synthesis. The drug has been shown to be effective in vitro against a variety of human carcinoma cell lines.</p>

<p>Quinapril is an angiotensin-converting enzyme (ACE) inhibitor prodrug that is used to treat hypertension and congestive heart failure. It blocks the conversion of angiotensin I to angiotensin II, resulting in vasodilation which lowers blood pressure.</p>

<p>Autocamtide-3-related inhibitory peptide is a calmodulin-dependent protein kinase II (CaMKII) inhibitor. AC3-I is derived from Autocamtide-3, a substrate for CaMKII, with the Thr-9 phosphorylation site substituted with Ala.CAMK represents a class of Ca2+/calmodulin-dependent protein kinase enzymes. CAMKs are activated by increases in the concentration of intracellular calcium ions (Ca2+) and transfers phosphates from ATP to defined serine or threonine residues in other proteins. Activated CAMK is involved in the phosphorylation of transcription factors and therefore, in the regulation of expression of responding genes.</p>

<p>The peptide IRW, characterised from egg protein, exhibits inhibitory properties against the angiotensin converting enzyme (ACE2) and could be used to prevent cardiovascular disease with further research. Treatment of hypertensive mice with IRW induced endothelium-dependent vasorelaxation and reduced vascular inflammation. The IRW tripeptide acts as anti-hypertensive by upregulating ACE2 activity via the Mas receptor (MasR) and upregulating Akt/eNOS signalling in the aorta. IRW also induces superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity. These may play a factor in IRW's role as an anti-inflammatory. IRW shows promise as a nutraceutical for inflammatory conditions and a tool for drug development in cardiovascular disease.</p>

<p>Cell permeable peptide which is able to activate phosphoinositide 3- kinase, for which it binds with high affinity to the p85 subunit. 740 Y-P also has mitogenic activity as it is able to induce mitosis in muscle cells, and promotes cell survival in neurones. PI 3- kinase's are a family of enzymes involved in many cellular pathways including cell proliferation, growth, differentiation, survival, motility, and intracellular trafficking. PI 3 Kinases are therefore also involved in many cancers.</p>

<p>AMARA peptide is a fragment containing the phosphorylation site for AMP activated protein kinase (AMPK) and is a substrate for all AMPK subfamily kinases. As such it is used to measure AMPK related kinase activity.</p>

<p>Axltide-is a substrate peptide for use in kinase assays and is based on the mouse insulin receptor substrate 1 (IRS1) (amino acid 979-989).IRS1 is a membrane-proximal adaptor protein, which binds to, and is phosphorylated by, the insulin receptor (IR) at its tyrosine residue. IRS1 transmits the extracellular signal for insulin to serine/threonine kinases, such as Akt which then deliver the signal into the cell to mediate the various actions of insulin.</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>Amino acids 487-496 of Poly(ADP-ribose) polymerase 1 (PARP1). PARP1 is a nuclear DNA repair enzyme that binds to DNA when damage is detected. PARP1 coordinates double and single strand break repair by first cleaving NAD+ into nicotinamide and ADP-ribose, and then synthesising poly-(ADP-ribose) (PAR) chains from ADP-ribose on target proteins (PARylation). PARylation of histone proteins mediates relaxation of the chromatin and recruitment of DNA-break repair enzymes.PARP1 can also act as a transcriptional co-activator, modulating the expression of itself and many other genes by direct binding to or PARylation of enhancers and promoters. PARP1 is also involved in maintaining mtDNA.PARP1 belongs to the PARP family which has 7 known and 10 putative members. PARP1 accounts for &gt;85% of the PARP activity in cellular systems.</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>eV1-2 is a selective εPKC inhibitor peptide which interferes with protein-protein interactions between the ϵPKC isozyme and its anchoring protein (ϵRACK). ϵPKC and ϵRACK regulate the contraction rate of heart muscle cells and provide protection from ischemia induced cell death. ϵV1-2 is derived from the C2 domain of ϵPKC, a region important for protein-protein interactions and thus acts as a competitive inhibitor of these interactions. The C2 region is well conserved between species, but different enough from other PKC isozymes to allow for targeted inhibition (ϵV1-2 is 88% identical between sea slugs and rat ϵPKC, yet only 36% identical between rat ϵPKC and rat θ´PKC). This peptide contains a C-terminal cysteine residue for conjugation to a carrier protein.</p>

<p>Amino acids 651-660 of Poly(ADP-ribose) polymerase 1 (PARP1). PARP1 is a nuclear DNA repair enzyme that binds to DNA when damage is detected. PARP1 coordinates double and single strand break repair by first cleaving NAD+ into nicotinamide and ADP-ribose, and then synthesising poly-(ADP-ribose) (PAR) chains from ADP-ribose on target proteins (PARylation). PARylation of histone proteins mediates the relaxation of the chromatin and recruitment of DNA-break repair enzymes.PARP1 can also act as a transcriptional co-activator, modulating the expression of itself and many other genes by direct binding to or PARylation of enhancers and promoters. PARP1 is also involved in maintaining mtDNA.PARP1 belongs to the PARP family which has 7 known and 10 putative members. PARP1 accounts for &gt;85% of the PARP activity in cellular systems.</p>

<p>Ile-Pro-Pro (IPP) has the ability to inhibit angiotensin-converting enzyme and stimulate the production of nitric oxide. It could be used to improve hypertension thus reducing the risk of cardiovascular diseases.</p>

<p>Potently inhibits PARP-1 and PARP-2 enzymes, orally bioavailable and crosses blood-brain barrier. Sensitises cancer cells to DNA-damaging chemotherapy and radiotherapy. Combination therapies investigated in clinical trials for solid and blood malignancies.</p>