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Phosphodiesterase (PDE) Phosphodiesterase (PDE) is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many other families of phosphodiesterases, including phospholipases C and D, autotaxin, sphingomyelin phosphodiesterase, DNases, RNases, and restriction endonucleases, as well as numerous less-well-characterized small-molecule phosphodiesterases. The cyclic nucleotide phosphodiesterases comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP. They regulate the localization, duration, and amplitude of cyclic nucleotide signaling within subcellular domains. PDEs are therefore important regulators ofsignal transduction mediated by these second messenger molecules. www.MedChemExpress.com 1 Phosphodiesterase (PDE) Inhibitors, Activators & Modulators (+)-Medioresinol Di-O-β-D-glucopyranoside (R)-(-)-Rolipram Cat. No.: HY-N8209 ((R)-Rolipram; (-)-Rolipram) Cat. No.: HY-16900A (+)-Medioresinol Di-O-β-D-glucopyranoside is a (R)-(-)-Rolipram is the R-enantiomer of Rolipram. lignan glucoside with strong inhibitory activity Rolipram is a selective inhibitor of of 3', 5'-cyclic monophosphate (cyclic AMP) phosphodiesterases PDE4 with IC50 of 3 nM, 130 nM phosphodiesterase. and 240 nM for PDE4A, PDE4B, and PDE4D, respectively. Purity: >98% Purity: 99.91% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 10 mM × 1 mL, 10 mg, 50 mg (R)-DNMDP (S)-(+)-Rolipram Cat. No.: HY-122751 ((+)-Rolipram; (S)-Rolipram) Cat. No.: HY-B0392 (R)-DNMDP is a potent and selective cancer cell (S)-(+)-Rolipram ((+)-Rolipram) is a cyclic cytotoxic agent. (R)-DNMDP, the R-form of DNMDP, AMP(cAMP)-specific phosphodiesterase (PDE) binds PDE3A directly. DNMDP binding to PDE3A inhibitor, with an IC50 of 1100 nM. promotes an interaction between PDE3A and Schlafen (S)-(+)-Rolipram can suppresse tumor necrosis 12 (SLFN12). factor-alpha (TNFα) production by human mononuclear cells. Purity: >98% Purity: 99.89% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 5 mg, 10 mg, 50 mg, 100 mg Size: 10 mM × 1 mL, 10 mg, 50 mg, 100 mg 3-O-Methylquercetin Acefylline Cat. No.: HY-N1860 (Theophyllineacetic acid; Theophylline-7-acetic acid) Cat. No.: HY-B1505 3-O-Methylquercetin (3-MQ), a main constituent of Acefylline (Theophyllineacetic acid), a xanthine Rhamnus nakaharai, inhibits total cAMP and derivative, is an adenosine receptor antagonist. cGMP-phosphodiesterase (PDE) of guinea pig Acefylline is a peptidylarginine deiminase (PAD) trachealis. 3-O-Methylquercetin (3-MQ) exhibits activator. Acefylline is also a bronchodilator, IC50 values of 31.9 μM 86.9 μM 18.6 μM and 1.6 μM which inhibits rat lung cAMP phosphodiesterase for PDE1, PDE5, PDE2 and PDE4, respectively. isoenzymes. Purity: >98% Purity: 99.89% Clinical Data: No Development Reported Clinical Data: Launched Size: 1 mg, 5 mg Size: 10 mM × 1 mL, 100 mg Acetildenafil AMG 579 Cat. No.: HY-13927 Cat. No.: HY-12913 Acetildenafil is a derivative of the AMG 579 is a potent, selective, and efficacious phosphodiesterase 5 (PDE5) inhibitor Sildenafil. inhibitor of phosphodiesterase 10A (PDE10A) with an IC50 of 0.1 nM. Purity: >98% Purity: 99.79% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg, 100 mg Amino Tadalafil Aminophylline Cat. No.: HY-117109 Cat. No.: HY-B0140 Amino Tadalafil is an analog of Tadalafil. Aminophylline is a competitive and non-selective Tadalafil is a potent inhibitor of phosphodiesterase (PDE) inhibitor. Aminophylline phosphodiesterase 5 (PDE5) with applications in is a competitive adenosine receptor antagonist. several conditions, including erectile Aminophylline has apulmonary vasodilator action as dysfunction, pulmonary arterial hypertension, and well as a bronchodilator action and has the lower urinary tract dysfunction. potential for asthma research. Purity: >98% Purity: 99.91% Clinical Data: No Development Reported Clinical Data: Launched Size: 1 mg, 5 mg Size: 10 mM × 1 mL, 100 mg, 500 mg 2 Tel: 609-228-6898 Fax: 609-228-5909 Email: [email protected] Amrinone AN3199 (Inamrinone) Cat. No.: HY-B1294 Cat. No.: HY-19830 Amrinone (Inamrinone) is a positive AN3199 is a PDE4 inhibitor with an IC50 of 94.5 inotropic-vasodilator agent. Amrinone is a nM. AN3199 can be used for the research of selective phosphodiesterase III inhibitor that inflammation-associated diseases such as asthma increases cyclic adenosine monophosphate by and chronic obstructive pulmonary disease (COPD). preventing its breakdown. Purity: ≥98.0% Purity: 99.67% Clinical Data: Launched Clinical Data: No Development Reported Size: 10 mM × 1 mL, 25 mg, 50 mg, 100 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg Anagrelide hydrochloride Apremilast (BL4162A) Cat. No.: HY-B0523A (CC-10004) Cat. No.: HY-12085 Anagrelide hydrochloride (BL4162A) is a drug used Apremilast (CC-10004) is an orally available for the treatment of essential thrombocytosis. inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4) with an IC50 of 74 nM. Apremilast inhibits TNF-α release by lipopolysaccharide (LPS) with an IC50 of 104 nM. Purity: 99.65% Purity: 99.87% Clinical Data: Launched Clinical Data: Launched Size: 10 mM × 1 mL, 10 mg, 50 mg, 100 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg Apremilast D5 ATX inhibitor 1 (CC-10004 D5) Cat. No.: HY-12085S Cat. No.: HY-111410 Apremilast D5 (CC-10004 D5) is a deuterium labeled ATX inhibitor 1 is a potent ATX (IC50=1.23 nM, Apremilast. Apremilast is an orally available FS-3 and 2.18 nM, bis-pNPP) inhibitor. inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4) with an IC50 of 74 nM. Apremilast inhibits TNF-α release by lipopolysaccharide (LPS) with an IC50 of 104 nM. Purity: >98% Purity: 99.75% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg, 100 mg ATX inhibitor 5 Autotaxin modulator 1 Cat. No.: HY-133019 Cat. No.: HY-12812 ATX inhibitor 5 is a potent and orally active Autotaxin modulator 1 is an autotaxin (ATX) enzyme autotaxin (ATX) inhibitor, with an IC50 of 15.3 inhibitor, extracted from patent WO 2014018881 A1, nM. ATX inhibitor 5 shows anti-hepatofibrosis Compound Example 12b. effects and reduces CCl4-induced hepatic fibrosis level prominently. Purity: 99.77% Purity: 98.93% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10 mM × 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg, 100 mg Autotaxin-IN-1 Autotaxin-IN-3 Cat. No.: HY-123637 Cat. No.: HY-135053 Autotaxin-IN-1 is a potent autotaxin inhibitor, Autotaxin-IN-3 is a Autotaxin(ATX) inhibitor with which has favorable potency (IC50=2.2 nM), PK an IC50 of 2.4 nM, compound 33, sourced from properties, and a robust PK/PD relationship. patent WO2018212534A1. Autotaxin-IN-1 is used in treatment of osteoarthritis pain. Purity: >98% Purity: 98.21% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg, 100 mg www.MedChemExpress.com 3 Autotaxin-IN-4 Autotaxin-IN-5 Cat. No.: HY-135088 Cat. No.: HY-135089 Autotaxin-IN-4 (compound 51), extracted from Autotaxin-IN-5 (compound 63), extracted from patent WO2018212534A1, is an Autotaxin inhibitor. patent WO2018212534A1, is an Autotaxin inhibitor. Autotaxin-IN-4 has the potential to treat Autotaxin-IN-5 has the potential to treat idiopathic pulmonary fibrosis. idiopathic pulmonary fibrosis. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 1 mg, 5 mg Avanafil Ayanin (TA1790) Cat. No.: HY-18252 Cat. No.: HY-N2913 Avanafil(TA-1790) is a potent and highly selective Ayanin is a bioflavonoid isolated from Croton phosphodiesterase-5(PDE-5) inhibitor(IC50=5.2 nM) schiedeanus Schlecht. Ayanin is a non-selective for erectile dysfunction; lower selectivity phosphodiesterase1-4 inhibitor and can be used for against PDE1, PDE6, and PDE11. the study of respiratory disease,such as allergic asthma et al. Purity: 98.01% Purity: >98% Clinical Data: Launched Clinical Data: No Development Reported Size: 10 mM × 1 mL, 50 mg, 100 mg, 500 mg Size: 1 mg, 5 mg Balipodect Bay 60-7550 (TAK-063) Cat. No.: HY-12472 (BAY 607550) Cat. No.: HY-14992 Balipodect (TAK-063) is a highly potent, selective Bay 60-7550 is a potent and selective PDE2 and orally active PDE10A inhibitor with IC50 of inhibitor with a Ki of 3.8 nM. 0.30 nM; >15000-fold selectivity over other PDEs. Purity: 98.69% Purity: 98.12% Clinical Data: Phase 2 Clinical Data: No Development Reported Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg, 100 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 100 mg BAY 73-6691 BAY 73-6691 racemate ((R)-BAY 73-6691) Cat. No.: HY-104028 Cat. No.: HY-104028A BAY 73-6691 ((R)-BAY 73-6691) is a potent, brain BAY 73-6691 racemate is a phosphodiesterase 9 penetrant, and selective PDE9A inhibitor. inhibitor extracted from patent WO 2017070293 A1. Purity: 99.81% Purity: 99.84% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10 mM × 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg, 100 mg BC11-38 BI-2545 Cat. No.: HY-108618 Cat. No.: HY-124772 BC11-38 is a potent, selective, and biologically BI-2545 is a potent autotaxin (ATX) inhibitor that active PDE11 inhibitor, with IC50s of 0.28 µM and significantly reduces LPA, with IC50s of 2.2 nM >100 µM for PDE11 and PDE1-10, respectively.
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  • ED Analogues Analysis

    ED Analogues Analysis

    UPLC-MS/MS for the Screening, Confirmation and Quantification of 32 Drugs illegally added to Herbal/Dietary Supplements for the Enhancement of Male Sexual Performance 1Salman Azimi*, 2Nayan Mistry and 2Michelle Wood 1Drug Quality Control Laboratory, Pharmacy & Drug Control Dept., Supreme Council of Health, PO Box 1919, Doha - Qatar. 2 Figure-5: Photographs of six positive samples. Forty-three suspected Waters Corporation, Atlas Park, Wythenshawe, Manchester, M22 5PP, UK. samples were analyzed in this study; 18 were found to be adulterated with ED drugs. ABSTRACT RESULTS & DISCUSSION The adulteration of herbal/dietary supplements with erectile dysfunction (ED) drugs and their analogues is reported For the purpose of screening , a spectral library for known ED drugs and analogues was prepared. Owing to recent reports Table 2: List of 32 compounds with retention times, and optimised MRM transitions parameters. Table-3: Summary of results for eight adulterated herbal/dietary samples. The screening results, including spectral match worldwide and is an increasing problem[1]. The sale of so-called 100%, ‘all-natural’ products has become a highly of increased availability of ‘all-in-one’/ ‘combination’ herbal products[2], we also added the naturally-occurring substances factors, RT data and final screening status ( = positive or - = negative) are presented, in addition to the quantitative data Retention Precursor Cone Quantifier Qualifier %CV (n=4) from the subsequent confirmatory analysis. profitable business for online pharmacies, however these products can pose a serious threat to consumers owing to the Icariin and yohimbine, the synthetic, dapoxetine (used for premature ejaculation) and testosterone. The library was CE CE Dwell LOQ undisclosed presence of approved/prescription drugs or the unknown safety and toxicity profile of unapproved ED drugs.
  • The Single Cyclic Nucleotide-Specific Phosphodiesterase of the Intestinal Parasite Giardia Lamblia Represents a Potential Drug Target

    The Single Cyclic Nucleotide-Specific Phosphodiesterase of the Intestinal Parasite Giardia Lamblia Represents a Potential Drug Target

    RESEARCH ARTICLE The single cyclic nucleotide-specific phosphodiesterase of the intestinal parasite Giardia lamblia represents a potential drug target Stefan Kunz1,2*, Vreni Balmer1, Geert Jan Sterk2, Michael P. Pollastri3, Rob Leurs2, Norbert MuÈ ller1, Andrew Hemphill1, Cornelia Spycher1¤ a1111111111 1 Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland, 2 Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute of Molecules, Medicines and Systems (AIMMS), Vrije a1111111111 Universiteit Amsterdam, Amsterdam, The Netherlands, 3 Department of Chemistry and Chemical Biology, a1111111111 Northeastern University, Boston, Massachusetts, United States of America a1111111111 a1111111111 ¤ Current address: Euresearch, Head Office Bern, Bern, Switzerland * [email protected] Abstract OPEN ACCESS Citation: Kunz S, Balmer V, Sterk GJ, Pollastri MP, Leurs R, MuÈller N, et al. (2017) The single cyclic Background nucleotide-specific phosphodiesterase of the Giardiasis is an intestinal infection correlated with poverty and poor drinking water quality, intestinal parasite Giardia lamblia represents a potential drug target. PLoS Negl Trop Dis 11(9): and treatment options are limited. According to the Center for Disease Control and Preven- e0005891. https://doi.org/10.1371/journal. tion, Giardia infections afflict nearly 33% of people in developing countries, and 2% of the pntd.0005891 adult population in the developed world. This study describes the single cyclic nucleotide- Editor: Aaron R. Jex, University of Melbourne, specific phosphodiesterase (PDE) of G. lamblia and assesses PDE inhibitors as a new gen- AUSTRALIA eration of anti-giardial drugs. Received: December 5, 2016 Accepted: August 21, 2017 Methods Published: September 15, 2017 An extensive search of the Giardia genome database identified a single gene coding for a class I PDE, GlPDE.