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Metabotropic Glutamate Receptors

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mGluR Metabotropic glutamate receptors mGluR (metabotropic glutamate receptor) is a type of glutamate receptor that are active through an indirect metabotropic process. They are members of thegroup C family of G-protein-coupled receptors, or GPCRs. Like all glutamate receptors, mGluRs bind with glutamate, an amino acid that functions as an excitatoryneurotransmitter. The mGluRs perform a variety of functions in the central and peripheral nervous systems: mGluRs are involved in learning, memory, anxiety, and the perception of pain. mGluRs are found in pre- and postsynaptic neurons in synapses of the hippocampus, cerebellum, and the cerebral cortex, as well as other parts of the brain and in peripheral tissues. Eight different types of mGluRs, labeled mGluR1 to mGluR8, are divided into groups I, II, and III. Receptor types are grouped based on receptor structure and physiological activity. www.MedChemExpress.com 1 mGluR Agonists, Antagonists, Inhibitors, Modulators & Activators (-)-Camphoric acid (1R,2S)-VU0155041 Cat. No.: HY-122808 Cat. No.: HY-14417A (-)-Camphoric acid is the less active enantiomer (1R,2S)-VU0155041, Cis regioisomer of VU0155041, is of Camphoric acid. Camphoric acid stimulates a partial mGluR4 agonist with an EC50 of 2.35 osteoblast differentiation and induces μM. glutamate receptor expression. Camphoric acid also significantly induced the activation of NF-κB and AP-1. Purity: ≥98.0% Purity: ≥98.0% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10 mM × 1 mL, 100 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 25 mg (2R,4R)-APDC (R)-ADX-47273 Cat. No.: HY-102091 Cat. No.: HY-13058B (2R,4R)-APDC is a selective group II metabotropic (R)-ADX-47273 is a potent mGluR5 positive glutamate receptors (mGluRs) agonist. allosteric modulator, with an EC50 of 168 nM for (2R,4R)-APDC has anticonvulsant and potentiation . neuroprotective effects. Purity: >98% Purity: 99.25% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 5 mg, 10 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg (RS)-MCPG (RS)-PPG (alpha-MCPG) Cat. No.: HY-100371 Cat. No.: HY-107514 (RS)-MCPG (alpha-MCPG) is a competitive and (RS)-PPG is a potent and selective agonist for selective group I/group II metabotropic group III mGluRs. The EC50s of 5.2 μM, 4.7 glutamate receptor (mGluR) antagonist. μM, 185 μM, and 0.2 μM for hmGluR4a, hmGluR6, (RS)-MCPG blocks theta-burst stimulation hmGluR7b, and hmGluR8a, respectively. (TBS)-induced shifts in both juvenile and neonatal Anticonvulsive and neuroprotective activity. rat hippocampal neurons. Purity: 99.05% Purity: >98% 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: 1 mg, 5 mg (S)-3,5-DHPG (S)-MCPG Cat. No.: HY-12598 ((+)-MCPG) Cat. No.: HY-100406 (S)-3,5-DHPG is a weak, but selective group I (S)-MCPG ((+)-MCPG) is a potent group I/II metabotropic glutamate receptors (mGluRs) metabotropic glutamate receptor (mGluRs) agonist with Ki values of 0.9 µM and 3.9 µM for antagonist and the active isomer of (RS)-MCPG mGluR1a and mGluR5a, respectively. (S)-3,5-DHPG (HY-100371). (S)-MCPG can be used for the study of exhibits anxiolytic activity in rats subjected to the function of mGluRs in spatial learning. hypoxia. Purity: ≥99.0% Purity: 98.80% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10 mM × 1 mL, 5 mg Size: 5 mg, 10 mg, 25 mg, 50 mg (±)-LY367385 3,3'-Difluorobenzaldazine Cat. No.: HY-135464 (DFB) Cat. No.: HY-14611 (±)-LY367385 is the racemate of LY367385. LY367385 3,3'-Difluorobenzaldazine (DFB) is a selective is a highly potent and selective mGluR1a positive allosteric modulator of mGluR5. antagonist. LY367385 has an IC50 of 8.8 μM for 3,3'-Difluorobenzaldazine potentiates 3- to 6-fold inhibits of quisqualate-induced phosphoinositide action for mGlu5 agonists (Glutamate, Quisqualate, (PI) hydrolysis, compared with > 100 μM for and 3,5-Dihydroxyphenylglycine), with EC50s in mGlu5a. the 2 to 5 μM range. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg Size: 1 mg, 5 mg 2 Tel: 609-228-6898 Fax: 609-228-5909 Email: [email protected] ADX-47273 ADX71743 Cat. No.: HY-13058 Cat. No.: HY-110278 ADX-47273 is a potent, selective and ADX71743 is a highly selective, noncompetitive and brain-penetrant mGluR5 positive allosteric brain-penetrant metabotropic glutamate receptor modulator (PAM), with an EC50 of 0.17 μM for 7 negative allosteric modulator (mGlu7 potentiation of glutamate (50 nM) response. NAM). ADX71743 has anxiolytic-like activity. ADX-47273 has antipsychotic and procognitive activities. Purity: 99.34% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg, 100 mg Size: 1 mg, 5 mg ADX88178 AMN082 Cat. No.: HY-18654 Cat. No.: HY-103565 ADX88178 is a potent metabotropic glutamate AMN082, a selective, orally active, and brain receptor 4 positive allosteric modulator penetrant mGluR7 agonist, directly activates (mGluR4 PAM) with an EC50 of 4 nM for human receptor signaling via an allosteric site in the mGluR4. transmembrane domain. Purity: 99.60% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg Size: 5 mg Auglurant AZD 2066 (VU0424238) Cat. No.: HY-16617 Cat. No.: HY-110255 Auglurant (VU0424238) is a novel and selective AZD 2066 is a selective, orally active and mGlu5 antagonist with an IC50 value of 11 nM brain-penetrant antagonist of mGluR5. AZD 2066 (rat) and an IC50 value of 14 nM (human). has antinociception effects. Auglurant (VU0424238) has an acceptable CNS penetration. Purity: 99.40% Purity: ≥99.0% Clinical Data: No Development Reported Clinical Data: Phase 2 Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg, 100 mg Size: 5 mg AZD 2066 hydrate AZD 9272 Cat. No.: HY-110255A Cat. No.: HY-110254 AZD 2066 hydrate is a selective, orally active and AZD 9272 is a brain penetrant mGluR5 brain-penetrant antagonist of mGluR5. AZD 2066 antagonist. hydrate has antinociception effects. Purity: ≥99.0% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 5 mg Size: 1 mg, 5 mg AZD-8529 AZD-8529 mesylate Cat. No.: HY-107457 Cat. No.: HY-107457A AZD-8529 is a potent, highly selective and orally AZD-8529 mesylate is a potent, highly selective bioavailable positive allosteric modulator of and orally bioavailable positive allosteric mGluR2, with an EC50 of 285 nM, and shows no modulator of mGluR2, with an EC50 of 285 nM, positive allosteric modulator responses at 20-25 M and shows no positive allosteric modulator on the mGluR1, 3, 4, 5, 6, 7, and 8 subtypes. responses at 20-25 M on the mGluR1, 3, 4, 5, 6, 7, and 8 subtypes. Purity: 98.43% Purity: 99.05% Clinical Data: Phase 2 Clinical Data: No Development Reported Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg www.MedChemExpress.com 3 Basimglurant Biphenylindanone A (RG7090; CTEP Derivative) Cat. No.: HY-15446 (BINA) Cat. No.: HY-15442 Basimglurant (RG7090) is a potent, selective and Biphenylindanone A (BINA) is a selective human orally available mGlu5 negative allosteric mGluR2 (hmGluR2) potentiator for the modulator with a Kd of 1.1 nM. treatment of many neurological disorders. Purity: 99.56% Purity: ≥99.0% Clinical Data: Phase 1 Clinical Data: No Development Reported Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg, 100 mg Size: 10 mM × 1 mL, 1 mg, 5 mg BMS-984923 BMT-145027 Cat. No.: HY-122559 Cat. No.: HY-100728 BMS-984923, a potent mGluR5 silent allosteric BMT-145027 is an mGluR5 positive allosteric modulator (SAM), with exquisite binding affinity modulator without inherent agonist activity, (Ki = 0.6 nM), exhibits good oral bioavailability exhibits an EC50 of 47 nM. and BBB penetration. Purity: >98% Purity: 98.19% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 5 mg, 10 mg, 50 mg CALP1 CALP1 TFA Cat. No.: HY-P1077 Cat. No.: HY-P1077A CALP1 is a calmodulin (CaM) agonist (Kd of CALP1 TFA is a calmodulin (CaM) agonist 88 µM) with binding to the CaM (Kd of 88 µM) with binding to the CaM EF-hand/Ca2+-binding site. CALP1 blocks calcium EF-hand/Ca2+-binding site. CALP1 TFA blocks calcium influx and apoptosis (IC50 of 44.78 µM) through influx and apoptosis (IC50 of 44.78 µM) through inhibition of calcium channel opening. inhibition of calcium channel opening. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 1 mg, 5 mg CDPPB CFMTI Cat. No.: HY-14569 Cat. No.: HY-100402 CDPPB is a potent, selective and brain penetrant CFMTI inhibits L-glutamate-induced intracellular positive allosteric modulator of the Ca2+ mobilization in CHO cells expressing human metabotropic glutamate receptor subtype 5 and rat mGluR1a, with IC50s of 2.6 and 2.3 nM, (mGluR5), with an EC50 of 27 nM in Chinese respectively. hamster ovary cells expressing human mGluR5. Purity: 98.05% Purity: ≥98.0% Clinical Data: No Development Reported 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, 25 mg, 50 mg, 100 mg CHPG CHPG sodium salt Cat. No.: HY-101364 Cat. No.: HY-101364A CHPG is a selective mGluR5 agonist, and CHPG sodium salt is a selective mGluR5 agonist, attenuates SO2-induced oxidative stress and and attenuates SO2-induced oxidative stress and inflammation through TSG-6/NF-κB pathway in BV2 inflammation through TSG-6/NF-κB pathway in BV2 microglial cells.
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  • Draft COMP Agenda 16-18 January 2018

    Draft COMP Agenda 16-18 January 2018

    12 January 2018 EMA/COMP/818236/2017 Inspections, Human Medicines Pharmacovigilance and Committees Committee for Orphan Medicinal Products (COMP) Draft agenda for the meeting on 16-18 January 2018 Chair: Bruno Sepodes – Vice-Chair: Lesley Greene 16 January 2018, 09:00-19:30, room 2F 17 January 2018, 08:30-19:30, room 2F 18 January 2018, 08:30-18:30, room 2F Health and safety information In accordance with the Agency’s health and safety policy, delegates are to be briefed on health, safety and emergency information and procedures prior to the start of the meeting. Disclaimers Some of the information contained in this agenda is considered commercially confidential or sensitive and therefore not disclosed. With regard to intended therapeutic indications or procedure scopes listed against products, it must be noted that these may not reflect the full wording proposed by applicants and may also vary during the course of the review. Additional details on some of these procedures will be published in the COMP meeting reports once the procedures are finalised. Of note, this agenda is a working document primarily designed for COMP members and the work the Committee undertakes. Note on access to documents Some documents mentioned in the agenda cannot be released at present following a request for access to documents within the framework of Regulation (EC) No 1049/2001 as they are subject to on- going procedures for which a final decision has not yet been adopted. They will become public when adopted or considered public according to the principles stated in the Agency policy on access to documents (EMA/127362/2006).
  • Biomolecules

    Biomolecules

    biomolecules Review Receptor Ligands as Helping Hands to L-DOPA in the Treatment of Parkinson’s Disease Fabio Del Bello , Mario Giannella, Gianfabio Giorgioni * , Alessandro Piergentili and Wilma Quaglia Scuola di Scienze del Farmaco e dei Prodotti della Salute, Università di Camerino, Via S. Agostino 1, 62032 Camerino, Italy; [email protected] (F.D.B.); [email protected] (M.G.); [email protected] (A.P.); [email protected] (W.Q.) * Correspondence: [email protected]; Tel.: +39-0737402368 Received: 18 March 2019; Accepted: 6 April 2019; Published: 9 April 2019 Abstract: Levodopa (LD) is the most effective drug in the treatment of Parkinson’s disease (PD). However, although it represents the “gold standard” of PD therapy, LD can cause side effects, including gastrointestinal and cardiovascular symptoms as well as transient elevated liver enzyme levels. Moreover, LD therapy leads to LD-induced dyskinesia (LID), a disabling motor complication that represents a major challenge for the clinical neurologist. Due to the many limitations associated with LD therapeutic use, other dopaminergic and non-dopaminergic drugs are being developed to optimize the treatment response. This review focuses on recent investigations about non-dopaminergic central nervous system (CNS) receptor ligands that have been identified to have therapeutic potential for the treatment of motor and non-motor symptoms of PD. In a different way, such agents may contribute to extending LD response and/or ameliorate LD-induced side effects. Keywords: Parkinson’s disease; levodopa therapy; levodopa-induced side effects; dopaminergic drugs; non-dopaminergic receptor ligands 1. Introduction Parkinson’s disease (PD), also known as idiopathic paralysis agitans, is one of the most frequent chronic neurodegenerative diseases worldwide.