stimulation

Vardenafil (Vivanza) is an oral therapy for the treatment of erectile dysfunction. It is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection. The tissue concentration of cGMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the human corpus cavernosum is the cGMPspecific phosphodiesterase type 5 (PDE5); therefore, the inhibition of PDE5 enhances erectile function by increasing the amount of cGMP.

Vardenafil hydrochloride trihydrate (BAY38-9456) is a new type PDE inhibitor with IC50 of 0.7 and 180 nM for PDE5 and PDE1, respectively.

Vardenafil hydrochloride is a New Phosphodiesterase Type 5(PDE5) Inhibitor, in the Treatment of Erectile Dysfunction in Men With Diabetes

Vardenafil dihydrochloride (Levitra) is a new type PDE inhibitor with IC50 of 0.7 and 180 nM for PDE5 and PDE1, respectively.

Adalimumab (anti-TNF-alpha) is the first fully human recombinant IgG1 monoclonal antibody that specifically targets human TNF-alpha.

Topterone (Win 17,665) is a potent topical antiandrogen that inhibits the stimulation of lumbar organ development by testosterone and dihydrotestosterone in castrated immature male hamsters.

VA-K-14 hydrochloride(VAK14 HCl) is a selective thyrotropin receptor (TSHR) antagonist (IC50= 12.3 μM) that inhibits TSHR stimulation by serum and monoclonal TSHR-stimulating antibodies from patients with GD and abrogates TSHR signaling.

KW-2450 free base is an orally bioavailable inhibitor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) tyrosine kinases with potential antineoplastic activity. IGF-1R IR inhibitor KW-2450 free base selectively binds to and inhibits the activities of IGF-1R and IR, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. IGF-R1 and IR tyrosine kinases, overexpressed in a variety of human cancers, play significant roles in the stimulation of cellular proliferation, oncogenic transformation, and suppression of apoptosis.

5-Hydroxy-1-methylhydantoin (HD-003) is an antioxidant potentially for the treatment of renal failure. A creatinine metabolite, 5-Hydroxy-1-methylhydantoin , a hydroxyl radical scavenger, has previously been shown to confer renoprotection by inhibiting the progression of chronic kidney disease in rats. 5-Hydroxy-1-methylhydantoin is a novel anti-oxidant drug completely suppressed the expression of B2-kinin receptors (B2KR) in response to high glucose (25 mM) stimulation in VSMC and was also shown to attenuate the effects of BK on VSMC remodeling. 5-Hydroxy-1-methylhydantoin inhibited the BK-induced increase in MAPK phosphorylation and attenuated the increase in connective tissue growth factor (CTGF) protein levels in VSMC. These findings suggest that 5-Hydroxy-1-methylhydantoin may confer vascular protection against high glucose concentrations and BK-stimulation to ameliorate vascular injury and remodeling through its anti-oxidant properties.

Addition of the Rhamnose (6-Deoxy-L-mannose)-rich polysaccharide, RROP-1, to normal human dermal fibroblasts (NHDFs) and human endothelial cells produced a dose-dependent stimulation of the calcium-signaling pathway, inducing fast and transient increases in Ca2 influx and intracellular free Ca2 level.

Gemfibrozil (CI-719) interacts with peroxisome proliferator-activated receptors (PPARalpha) resulting in PPARalpha-mediated stimulation of fatty acid oxidation and an increase in lipoprotein lipase (LPL) synthesis. Gemfibrozil is a fibric acid derivative with hypolipidemic effects. This enhances triglyceride-rich lipoprotein clearance and reduces the expression of apolipoprotein C-III (apoC-III). The reduction in hepatic production of apoC-III result in the subsequent reduction of serum levels of very-low-density-lipoprotein cholesterol (VLDL-C). In addition, gemfibrozil-mediated PPARalpha stimulation of apoA-I and apoA-II expression results in an increase in high-density lipoprotein cholesterol (HDL-C).

Cepharanthine (NSC-623442) is a natural alkaloid that inhibits TNF-α-mediated NFκB stimulation, plasma membrane lipid peroxidation, and platelet aggregation, as well as cytokine production. Cepharanthine exhibits anti-inflammatory, antioxidant, and antitumor activities.

Tropicamide (Ro 1-7683) is a synthetic muscarinic antagonist with anticholinergic properties similar to atropine. Upon ocular administration, it binds to and blocks muscarinic receptors in the sphincter and ciliary muscles, inhibiting cholinergic responses and causing pupil dilation and ciliary muscle paralysis. Tropicamide is used as a diagnostic agent to induce short-duration mydriasis and cycloplegia.

Arecoline hydrobromide (Arecoline HBr) is a muscarinic acetylcholine receptor agonist.

Neocuproine is a copper(I) chelator that enhances the purinergic component of vasoconstriction induced by electric field stimulation, and is often used as a ligand reagent and copper ion detector.Neocuproine forms stable complexes with copper ions and can play a catalytic role in certain chemical reactions and analytical methods.Neocuproine acts as a redox-active on the iron and cobalt ligand platform for protection against oxidative damage in NSC34 cells.

Tacrolimus monohydrate (LCP-Tacro) is a macrolide from the culture broth of a strain of Streptomyces tsukubaensis, binds to FK506 binding protein (FKBP) to form a complex. Tacrolimus inhibits calcineurin phosphatase, which inhibits T-lymphocyte signal transduction and IL-2 transcription. Immunosuppressive properties. It prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro and has strong immunosuppressive activity in vivo.

Bisdemethoxycurcumin (Curcumin III) is a natural demethoxy derivative of curcumin. It is a potent activator of macrophage phagocytosis, interacting with 1α, 25-dihydroxy vitamin D3 to stimulate amyloid-β clearance by macrophages (optimal stimulation at 100 nM BDMC) [1]. More stable than curcumin in physiological media, BDMC suppresses proliferation of cancer cells [2]. It down-regulates the transcriptional coactivator p300, suppressing the Wnt β-catenin pathway, and inhibits LPS induction of iNOS expression [3].

Atropine (DL-Hyoscyamine) Sulfate is the sulfate salt of atropine, a naturally-occurring alkaloid isolated from the plant Atropa belladonna. Atropine functions as a sympathetic, competitive antagonist of muscarinic cholinergic receptors, thereby abolishing the effects of parasympathetic stimulation.

LJI308 is a potent, and pan-RSK (p90 ribosomal S6 kinase) inhibitor with IC50 of 6 nM, 4 nM, and 13 nM for RSK1, RSK2, and RSK3, respectively.

1. β-Anhydroicaritin exhibits immunosuppressive effect on the mouse macrophages stimulated by LPS. 2. β-Anhydroicaritin phytosomes can inhibit enhanced bone turnover induced by ovariectomy, improve BMD the biomechanical properties of vertebrae, without any stimulation on uterus. 3. β-Anhydroicaritin possesses significant protective effects on the zymosan-induced peritonitis mice, which might be associated with the regulation of Ca(2+); influx in macrophages and iNOS expression.

Talabostat mesylate (PT100) is an orally active, selective inhibitor of dipeptidyl peptidases IV (DPP4, IC50: 0.18 nM), including tumor-associated fibroblast activation protein. This agent may also stimulate the production of colony stimulating factors, such as granulocyte colony-stimulating factor (G-CSF), resulting in the stimulation of hematopoiesis.

1. Kuwanon G (Moracenin B) as dual inhibitors of PTP1B and α-glucosidase enzymes, as well as insulin sensitizers, it may potentially be utilized as an effective treatment for Type II diabetes mellitus. 2. Kuwanon G has anti-inflammatory activity, it can attenuate atherosclerosis through inhibiting foam cell formation and inflammatory response. 3. Kuwanon G is a potent inhibitor of Mycobacterium tuberculosis protein tyrosine phosphatase B. 4. Kuwanon G shows acetylcholinesterase (AChE) and butyrylcholinesterase(BChE) inhibitory activities, it may be a promising candidate for preventive and therapeutic agents for Alzheimer's disease. 5. Kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. 6. Kuwanon G has antibacterial activity against oral pathogens. 7. Kuwanon G is a specific antagonist for the GRP-preferring receptor and can be useful for studying the physiological and pathological role of GRP.

BPTU (BMS-646786) is an allosteric antagonist of P2Y1 (EC50 = 0.06-0.3 μM). Non-nucleotide ligand. Binds receptor outside of the helical bundle. Blocks inhibition of spontaneous contraction of rat and mouse colon induced by electrical field stimulation, nicotine and P2Y agonists. Antithrombotic; reduces platelet aggregation.

Compound 1T-0216 is a blocker of AKT1-FAK interactions and reduces stimulation of FAK phosphorylation by extracellular stress in human SW620 colon cancer cells without affecting basal FAK phosphorylation.