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  1. Article ; Online: Epileptic Encephalopathy

    Hernandez, Ciria C / Hu, Ningning / Shen, Wangzhen / Macdonald, Robert L

    Biomolecules

    2023  Volume 13, Issue 12

    Abstract: Variants in ... ...

    Abstract Variants in the
    MeSH term(s) Humans ; Receptors, GABA-A/metabolism ; Mutation, Missense ; Mutation ; Seizures ; Brain Diseases
    Chemical Substances Receptors, GABA-A
    Language English
    Publishing date 2023-12-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom13121790
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  2. Article ; Online: Targeting the central melanocortin system for the treatment of metabolic disorders.

    Sweeney, Patrick / Gimenez, Luis E / Hernandez, Ciria C / Cone, Roger D

    Nature reviews. Endocrinology

    2023  Volume 19, Issue 9, Page(s) 507–519

    Abstract: A large body of preclinical and clinical data shows that the central melanocortin system is a promising therapeutic target for treating various metabolic disorders such as obesity and cachexia, as well as anorexia nervosa. Setmelanotide, which functions ... ...

    Abstract A large body of preclinical and clinical data shows that the central melanocortin system is a promising therapeutic target for treating various metabolic disorders such as obesity and cachexia, as well as anorexia nervosa. Setmelanotide, which functions by engaging the central melanocortin circuitry, was approved by the FDA in 2020 for use in certain forms of syndromic obesity. Furthermore, the FDA approvals in 2019 of two peptide drugs targeting melanocortin receptors for the treatment of generalized hypoactive sexual desire disorder (bremelanotide) and erythropoietic protoporphyria-associated phototoxicity (afamelanotide) demonstrate the safety of this class of peptides. These approvals have also renewed excitement in the development of therapeutics targeting the melanocortin system. Here, we review the anatomy and function of the melanocortin system, discuss progress and challenges in developing melanocortin receptor-based therapeutics, and outline potential metabolic and behavioural disorders that could be addressed using pharmacological agents targeting these receptors.
    MeSH term(s) Humans ; Melanocortins/therapeutic use ; Sexual Dysfunctions, Psychological/drug therapy ; Sexual Dysfunctions, Psychological/metabolism ; Obesity/drug therapy ; Cachexia ; Metabolic Diseases/drug therapy
    Chemical Substances Melanocortins
    Language English
    Publishing date 2023-06-26
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2489381-X
    ISSN 1759-5037 ; 1759-5029
    ISSN (online) 1759-5037
    ISSN 1759-5029
    DOI 10.1038/s41574-023-00855-y
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  3. Article ; Online: The unique structural characteristics of the Kir 7.1 inward rectifier potassium channel: a novel player in energy homeostasis control.

    Hernandez, Ciria C / Gimenez, Luis E / Dahir, Naima S / Peisley, Alys / Cone, Roger D

    American journal of physiology. Cell physiology

    2023  Volume 324, Issue 3, Page(s) C694–C706

    Abstract: The inward rectifier potassium channel Kir7.1, encoded by ... ...

    Abstract The inward rectifier potassium channel Kir7.1, encoded by the
    MeSH term(s) Humans ; Mutation ; Neurons/metabolism ; Potassium/metabolism ; Potassium Channels, Inwardly Rectifying/genetics ; Potassium Channels, Inwardly Rectifying/metabolism ; Protein Domains
    Chemical Substances Potassium (RWP5GA015D) ; Potassium Channels, Inwardly Rectifying ; KCNJ13 protein, human
    Language English
    Publishing date 2023-01-30
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 392098-7
    ISSN 1522-1563 ; 0363-6143
    ISSN (online) 1522-1563
    ISSN 0363-6143
    DOI 10.1152/ajpcell.00335.2022
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  4. Article ; Online: A structural look at GABA

    Hernandez, Ciria C / Macdonald, Robert L

    Brain research

    2019  Volume 1714, Page(s) 234–247

    Abstract: Understanding the genetic variation in ... ...

    Abstract Understanding the genetic variation in GABA
    MeSH term(s) Epilepsy/genetics ; Epilepsy/physiopathology ; Epileptic Syndromes/genetics ; Epileptic Syndromes/metabolism ; Epileptic Syndromes/physiopathology ; Humans ; Mutation/genetics ; Receptors, GABA-A/genetics ; Receptors, GABA-A/metabolism ; Receptors, GABA-A/physiology ; Structure-Activity Relationship
    Chemical Substances Receptors, GABA-A
    Language English
    Publishing date 2019-03-07
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1200-2
    ISSN 1872-6240 ; 0006-8993
    ISSN (online) 1872-6240
    ISSN 0006-8993
    DOI 10.1016/j.brainres.2019.03.004
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  5. Article ; Online: GABRG2

    Hernandez, Ciria C / Shen, Yanwen / Hu, Ningning / Shen, Wangzhen / Narayanan, Vinodh / Ramsey, Keri / He, Wen / Zou, Liping / Macdonald, Robert L

    Biomolecules

    2023  Volume 13, Issue 3

    Abstract: Febrile seizures (FS) are the most common form of epilepsy in children between six months and five years of age. FS is a self-limited type of fever-related seizure. However, complicated prolonged FS can lead to complex partial epilepsy. We found that ... ...

    Abstract Febrile seizures (FS) are the most common form of epilepsy in children between six months and five years of age. FS is a self-limited type of fever-related seizure. However, complicated prolonged FS can lead to complex partial epilepsy. We found that among the GABA
    MeSH term(s) Humans ; Seizures, Febrile/genetics ; Receptors, GABA-A/genetics ; Epilepsies, Myoclonic/genetics ; Epilepsy/genetics ; Mutation, Missense ; Mutation
    Chemical Substances Receptors, GABA-A ; GABRG2 protein, human
    Language English
    Publishing date 2023-02-22
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom13030414
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  6. Article ; Online: Novel Cocrystal Structures of Peptide Antagonists Bound to the Human Melanocortin Receptor 4 Unveil Unexplored Grounds for Structure-Based Drug Design.

    Gimenez, Luis E / Martin, Charlotte / Yu, Jing / Hollanders, Charlie / Hernandez, Ciria C / Wu, Yiran / Yao, Deqiang / Han, Gye Won / Dahir, Naima S / Wu, Lijie / Van der Poorten, Olivier / Lamouroux, Arthur / Mannes, Morgane / Zhao, Suwen / Tourwé, Dirk / Stevens, Raymond C / Cone, Roger D / Ballet, Steven

    Journal of medicinal chemistry

    2024  Volume 67, Issue 4, Page(s) 2690–2711

    Abstract: Melanocortin 4 receptor (MC4-R) antagonists are actively sought for treating cancer cachexia. We determined the structures of complexes ... ...

    Abstract Melanocortin 4 receptor (MC4-R) antagonists are actively sought for treating cancer cachexia. We determined the structures of complexes with
    MeSH term(s) Humans ; Receptor, Melanocortin, Type 4 ; Peptides/pharmacology ; Ligands ; Drug Design ; Receptor, Melanocortin, Type 3 ; Receptors, Melanocortin
    Chemical Substances Receptor, Melanocortin, Type 4 ; Peptides ; Ligands ; Receptor, Melanocortin, Type 3 ; Receptors, Melanocortin
    Language English
    Publishing date 2024-02-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c01822
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    Zs.B 151: Show issues Location:
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  7. Article ; Online: Development of an automated screen for Kv7.2 potassium channels and discovery of a new agonist chemotype.

    Hernandez, Ciria C / Tarfa, Rahilla A / Miguel I Limcaoco, Jose / Liu, Ruiting / Mondal, Pravat / Hill, Clare / Keith Duncan, R / Tzounopoulos, Thanos / Stephenson, Corey R J / O'Meara, Matthew J / Wipf, Peter

    Bioorganic & medicinal chemistry letters

    2022  Volume 71, Page(s) 128841

    Abstract: To identify pore domain ligands on Kv7.2 potassium ion channels, we compared wild-type (WT) and W236L mutant Kv7.2 channels in a series of assays with previously validated and novel agonist chemotypes. Positive controls were retigabine, flupirtine, and ... ...

    Abstract To identify pore domain ligands on Kv7.2 potassium ion channels, we compared wild-type (WT) and W236L mutant Kv7.2 channels in a series of assays with previously validated and novel agonist chemotypes. Positive controls were retigabine, flupirtine, and RL-81; i.e. Kv7.2 channel activators that significantly shift voltage-dependent activation to more negative potentials (ΔV
    MeSH term(s) KCNQ Potassium Channels/genetics ; KCNQ Potassium Channels/metabolism ; KCNQ2 Potassium Channel/genetics ; KCNQ2 Potassium Channel/metabolism
    Chemical Substances KCNQ Potassium Channels ; KCNQ2 Potassium Channel
    Language English
    Publishing date 2022-06-04
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1063195-1
    ISSN 1464-3405 ; 0960-894X
    ISSN (online) 1464-3405
    ISSN 0960-894X
    DOI 10.1016/j.bmcl.2022.128841
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  8. Article ; Online: Dravet syndrome-associated mutations in

    Hernandez, Ciria C / Tian, XiaoJuan / Hu, Ningning / Shen, Wangzhen / Catron, Mackenzie A / Yang, Ying / Chen, Jiaoyang / Jiang, Yuwu / Zhang, Yuehua / Macdonald, Robert L

    Brain communications

    2021  Volume 3, Issue 2, Page(s) fcab033

    Abstract: Dravet syndrome is a rare, catastrophic epileptic encephalopathy that begins in the first year of life, usually with febrile or afebrile hemiclonic or generalized tonic-clonic seizures followed by status epilepticus. ...

    Abstract Dravet syndrome is a rare, catastrophic epileptic encephalopathy that begins in the first year of life, usually with febrile or afebrile hemiclonic or generalized tonic-clonic seizures followed by status epilepticus.
    Language English
    Publishing date 2021-03-11
    Publishing country England
    Document type Journal Article
    ISSN 2632-1297
    ISSN (online) 2632-1297
    DOI 10.1093/braincomms/fcab033
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  9. Article ; Online: Reply.

    Janve, Vaishali S / Hernandez, Ciria C / Verdier, Kelienne M / Hu, Ningning / Macdonald, Robert L

    Annals of neurology

    2016  Volume 80, Issue 2, Page(s) 312–313

    Language English
    Publishing date 2016-06-24
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 80362-5
    ISSN 1531-8249 ; 0364-5134
    ISSN (online) 1531-8249
    ISSN 0364-5134
    DOI 10.1002/ana.24701
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  10. Article ; Online: Phosphatidylinositol 4,5-bisphosphate (PIP

    Choveau, Frank S / De la Rosa, Victor / Bierbower, Sonya M / Hernandez, Ciria C / Shapiro, Mark S

    The Journal of biological chemistry

    2018  Volume 293, Issue 50, Page(s) 19411–19428

    Abstract: Phosphatidylinositol 4,5-bisphosphate ( ... ...

    Abstract Phosphatidylinositol 4,5-bisphosphate (PIP
    MeSH term(s) Amino Acid Sequence ; Animals ; CHO Cells ; Cricetulus ; Cytoplasm/metabolism ; Humans ; KCNQ3 Potassium Channel/chemistry ; KCNQ3 Potassium Channel/genetics ; KCNQ3 Potassium Channel/metabolism ; Models, Molecular ; Mutation ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Protein Binding ; Protein Conformation, alpha-Helical ; Protein Domains
    Chemical Substances KCNQ3 Potassium Channel ; Phosphatidylinositol 4,5-Diphosphate
    Language English
    Publishing date 2018-10-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.RA118.005401
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