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Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure.

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Title: Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure.
Authors: Granberg KL; Medicinal Chemistry, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden., Sakamaki S; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan., Larsson N; Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden., Bergström F; Drug Metabolism and Pharmacokinetics (DMPK), Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden., Fuchigami R; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan., Niwa Y; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan., Ryberg E; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden., Backmark A; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden., Kato H; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan., Miyazaki S; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan., Iguchi K; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan., Sakamoto T; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan., Persson M; Cardiovascular, Renal and Metabolism Safety, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden., Idei A; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan., Prieto Garcia L; Drug Metabolism and Pharmacokinetics (DMPK), Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden., Villar IC; Regulatory Toxicology & Safety Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, Cambridge CB2 0AA, U.K., Gradén H; Medicinal Chemistry, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden., Bergonzini G; Compound Synthesis and Management, Discovery Sciences, R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden., Arvidsson T; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden., Fujita T; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan., Althage M; Translational Science and Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), Biopharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden., Ulander J; Data Science and Modelling, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden., Kimura J; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan., Yoneda H; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan., Fjellström O; Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), Biopharmaceutical, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden., Mochida H; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan., Lal M; Bioscience Renal, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), Biopharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.
Source: Journal of medicinal chemistry [J Med Chem] 2024 Mar 28; Vol. 67 (6), pp. 4419-4441. Date of Electronic Publication: 2024 Mar 19.
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Journal Info: Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE
Database: MEDLINE Ultimate
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PubType: Academic Journal
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  Data: Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure.
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  Data: <searchLink fieldCode="AU" term="%22Granberg+KL%22">Granberg KL</searchLink>; Medicinal Chemistry, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Sakamaki+S%22">Sakamaki S</searchLink>; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan.<br /><searchLink fieldCode="AU" term="%22Larsson+N%22">Larsson N</searchLink>; Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Bergström+F%22">Bergström F</searchLink>; Drug Metabolism and Pharmacokinetics (DMPK), Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Fuchigami+R%22">Fuchigami R</searchLink>; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan.<br /><searchLink fieldCode="AU" term="%22Niwa+Y%22">Niwa Y</searchLink>; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan.<br /><searchLink fieldCode="AU" term="%22Ryberg+E%22">Ryberg E</searchLink>; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Backmark+A%22">Backmark A</searchLink>; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Kato+H%22">Kato H</searchLink>; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan.<br /><searchLink fieldCode="AU" term="%22Miyazaki+S%22">Miyazaki S</searchLink>; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan.<br /><searchLink fieldCode="AU" term="%22Iguchi+K%22">Iguchi K</searchLink>; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan.<br /><searchLink fieldCode="AU" term="%22Sakamoto+T%22">Sakamoto T</searchLink>; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan.<br /><searchLink fieldCode="AU" term="%22Persson+M%22">Persson M</searchLink>; Cardiovascular, Renal and Metabolism Safety, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Idei+A%22">Idei A</searchLink>; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan.<br /><searchLink fieldCode="AU" term="%22Prieto+Garcia+L%22">Prieto Garcia L</searchLink>; Drug Metabolism and Pharmacokinetics (DMPK), Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Villar+IC%22">Villar IC</searchLink>; Regulatory Toxicology & Safety Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, Cambridge CB2 0AA, U.K.<br /><searchLink fieldCode="AU" term="%22Gradén+H%22">Gradén H</searchLink>; Medicinal Chemistry, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Bergonzini+G%22">Bergonzini G</searchLink>; Compound Synthesis and Management, Discovery Sciences, R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Arvidsson+T%22">Arvidsson T</searchLink>; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Fujita+T%22">Fujita T</searchLink>; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan.<br /><searchLink fieldCode="AU" term="%22Althage+M%22">Althage M</searchLink>; Translational Science and Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), Biopharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Ulander+J%22">Ulander J</searchLink>; Data Science and Modelling, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Kimura+J%22">Kimura J</searchLink>; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan.<br /><searchLink fieldCode="AU" term="%22Yoneda+H%22">Yoneda H</searchLink>; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan.<br /><searchLink fieldCode="AU" term="%22Fjellström+O%22">Fjellström O</searchLink>; Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), Biopharmaceutical, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Mochida+H%22">Mochida H</searchLink>; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan.<br /><searchLink fieldCode="AU" term="%22Lal+M%22">Lal M</searchLink>; Bioscience Renal, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), Biopharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83 Mölndal, Sweden.
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