Discovery of a Potent, Selective, and Orally Available MTHFD2 Inhibitor (DS18561882) with in Vivo Antitumor Activity.

Administration, Oral Aminohydrolases / antagonists & inhibitors Animals Antineoplastic Agents / administration & dosage Breast Neoplasms / drug therapy Cell Line, Tumor Cell Membrane Permeability / drug effects Crystallography, X-Ray Female Humans Male Methylenetetrahydrofolate Dehydrogenase (NADP) / antagonists & inhibitors Mice, Inbred BALB C Multifunctional Enzymes / antagonists & inhibitors Structure-Activity Relationship Xenograft Model Antitumor Assays

Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
27 11 2019
Historique:
pubmed: 23 10 2019
medline: 15 7 2020
entrez: 23 10 2019
Statut: ppublish

Résumé

We report the discovery of a potent and isozyme-selective MTHFD2 inhibitor, DS18561882 (

Identifiants

DOI: 10.1021/acs.jmedchem.9b01113 PMID: 31638799
pubmed: 31638799
doi: 10.1021/acs.jmedchem.9b01113
doi:

Substances chimiques

Antineoplastic Agents 0
MTHFD2 protein, human 0
Multifunctional Enzymes 0
Methylenetetrahydrofolate Dehydrogenase (NADP) EC 1.5.1.5
Aminohydrolases EC 3.5.4.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

10204-10220

Auteurs

Junya Kawai (J)

R&D Division , Daiichi Sankyo Co., Ltd. , 1-2-58 Hiromachi , Shinagawa-ku, Tokyo 140-8710 , Japan.
ORCID: 0000-0002-8188-5765

Tadashi Toki (T)

R&D Division , Daiichi Sankyo Co., Ltd. , 1-2-58 Hiromachi , Shinagawa-ku, Tokyo 140-8710 , Japan.

Masahiro Ota (M)

Daiichi Sankyo RD Novare Co., Ltd. , 1-16-13 Kitakasai , Edogawa-ku, Tokyo 134-8630 , Japan.

Hidekazu Inoue (H)

R&D Division , Daiichi Sankyo Co., Ltd. , 1-2-58 Hiromachi , Shinagawa-ku, Tokyo 140-8710 , Japan.

Yoshimi Takata (Y)

R&D Division , Daiichi Sankyo Co., Ltd. , 1-2-58 Hiromachi , Shinagawa-ku, Tokyo 140-8710 , Japan.

Takashi Asahi (T)

R&D Division , Daiichi Sankyo Co., Ltd. , 1-2-58 Hiromachi , Shinagawa-ku, Tokyo 140-8710 , Japan.

Makoto Suzuki (M)

Daiichi Sankyo RD Novare Co., Ltd. , 1-16-13 Kitakasai , Edogawa-ku, Tokyo 134-8630 , Japan.

Takashi Shimada (T)

Daiichi Sankyo RD Novare Co., Ltd. , 1-16-13 Kitakasai , Edogawa-ku, Tokyo 134-8630 , Japan.

Kaori Ono (K)

Daiichi Sankyo RD Novare Co., Ltd. , 1-16-13 Kitakasai , Edogawa-ku, Tokyo 134-8630 , Japan.

Kanae Suzuki (K)

R&D Division , Daiichi Sankyo Co., Ltd. , 1-2-58 Hiromachi , Shinagawa-ku, Tokyo 140-8710 , Japan.

Sachiko Takaishi (S)

R&D Division , Daiichi Sankyo Co., Ltd. , 1-2-58 Hiromachi , Shinagawa-ku, Tokyo 140-8710 , Japan.

Hitoshi Ohki (H)

R&D Division , Daiichi Sankyo Co., Ltd. , 1-2-58 Hiromachi , Shinagawa-ku, Tokyo 140-8710 , Japan.

Satoshi Matsui (S)

R&D Division , Daiichi Sankyo Co., Ltd. , 1-2-58 Hiromachi , Shinagawa-ku, Tokyo 140-8710 , Japan.

Shinji Tsutsumi (S)

R&D Division , Daiichi Sankyo Co., Ltd. , 1-2-58 Hiromachi , Shinagawa-ku, Tokyo 140-8710 , Japan.

Yasuhide Hirota (Y)

R&D Division , Daiichi Sankyo Co., Ltd. , 1-2-58 Hiromachi , Shinagawa-ku, Tokyo 140-8710 , Japan.

Kiyoshi Nakayama (K)

Daiichi Sankyo Co., Ltd. , 3-5-1 Nihonbashi-honcho , Chuo-ku, Tokyo 103-8426 , Japan.

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Classifications MeSH

questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Administration par voie orale › Discovery of a Potent, Selective, and Orally...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Aminohydrolases › Discovery of a Potent, Selective, and Orally...
questionsmedicales.fr › Eucaryotes › Animaux › Discovery of a Potent, Selective, and Orally...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Discovery of a Potent, Selective, and Orally...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › Discovery of a Potent, Selective, and Orally...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Discovery of a Potent, Selective, and Orally...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Perméabilité des membranes cellulaires › Discovery of a Potent, Selective, and Orally...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Cristallographie aux rayons X › Discovery of a Potent, Selective, and Orally...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Discovery of a Potent, Selective, and Orally...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Oxidoreductases acting on CH-NH group donors › Methylenetetrahydrofolate Dehydrogenase (NADP) › Discovery of a Potent, Selective, and Orally...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée BALB C › Discovery of a Potent, Selective, and Orally...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Enzymes multifonctionnelles › Discovery of a Potent, Selective, and Orally...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › Discovery of a Potent, Selective, and Orally...
questionsmedicales.fr › Techniques d'investigation › Transplantation tumorale › Tests d'activité antitumorale sur modèle de xénogreffe › Discovery of a Potent, Selective, and Orally...