PF-07059013: A Noncovalent Modulator of Hemoglobin for Treatment of Sickle Cell Disease.

Anemia, Sickle Cell / drug therapy Animals Erythrocytes / metabolism Hemoglobin A / drug effects Hemoglobin, Sickle / drug effects Mice Oxygen / metabolism Quinolines / chemistry

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:
14 01 2021
Historique:
pubmed: 29 12 2020
medline: 9 3 2021
entrez: 28 12 2020
Statut: ppublish

Résumé

Sickle cell disease (SCD) is a genetic disorder caused by a single point mutation (β6 Glu → Val) on the β-chain of adult hemoglobin (HbA) that results in sickled hemoglobin (HbS). In the deoxygenated state, polymerization of HbS leads to sickling of red blood cells (RBC). Several downstream consequences of polymerization and RBC sickling include vaso-occlusion, hemolytic anemia, and stroke. We report the design of a noncovalent modulator of HbS, clinical candidate PF-07059013 (

Identifiants

DOI: 10.1021/acs.jmedchem.0c01518 PMID: 33356244
pubmed: 33356244
doi: 10.1021/acs.jmedchem.0c01518
doi:

Substances chimiques

Hemoglobin, Sickle 0
Quinolines 0
Hemoglobin A 9034-51-9
Oxygen S88TT14065

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

326-342

Auteurs

Ariamala Gopalsamy (A)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.

Ann E Aulabaugh (AE)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Amey Barakat (A)

Rare Diseases Research Unit, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.

Kevin C Beaumont (KC)

Primary Pharmacology Group, Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.

Shawn Cabral (S)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Daniel P Canterbury (DP)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Agustin Casimiro-Garcia (A)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.
ORCID: 0000-0001-9618-2547

Jeanne S Chang (JS)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Ming Z Chen (MZ)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Chulho Choi (C)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Robert L Dow (RL)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.
ORCID: 0000-0002-3045-5503

Olugbeminiyi O Fadeyi (OO)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Xidong Feng (X)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Scott P France (SP)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.
ORCID: 0000-0003-1679-6165

Roger M Howard (RM)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.
ORCID: 0000-0001-5884-4896

Jay M Janz (JM)

Rare Diseases Research Unit, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.

Jayasankar Jasti (J)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Reema Jasuja (R)

Rare Diseases Research Unit, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.

Lyn H Jones (LH)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.
ORCID: 0000-0002-8388-5865

Amanda King-Ahmad (A)

Primary Pharmacology Group, Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Kelly M Knee (KM)

Rare Diseases Research Unit, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.

Jeffrey T Kohrt (JT)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Chris Limberakis (C)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Spiros Liras (S)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.
ORCID: 0000-0002-0334-2095

Carlos A Martinez (CA)

Medicinal Sciences, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Kim F McClure (KF)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.

Arjun Narayanan (A)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.

Jatin Narula (J)

Primary Pharmacology Group, Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.

Jonathan J Novak (JJ)

Primary Pharmacology Group, Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Thomas N O'Connell (TN)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Mihir D Parikh (MD)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

David W Piotrowski (DW)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.
ORCID: 0000-0002-4659-6300

Olga Plotnikova (O)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Ralph P Robinson (RP)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.
ORCID: 0000-0002-4066-5299

Parag V Sahasrabudhe (PV)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Raman Sharma (R)

Primary Pharmacology Group, Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Benjamin A Thuma (BA)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Dipy Vasa (D)

Drug Product Design, Pfizer Worldwide Research and Development, Cambridge, Massachusetts 02139, United States.

Liuqing Wei (L)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

A Zane Wenzel (AZ)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Jane M Withka (JM)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Jun Xiao (J)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Hatice G Yayla (HG)

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

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Classifications MeSH

questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Hémoglobinopathies › Drépanocytose › PF-07059013: A Noncovalent Modulator of...
questionsmedicales.fr › Eucaryotes › Animaux › PF-07059013: A Noncovalent Modulator of...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Sang › Cellules sanguines › Érythrocytes › PF-07059013: A Noncovalent Modulator of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Hémoprotéines › Globines › Hémoglobines › Hémoglobine A › PF-07059013: A Noncovalent Modulator of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Hémoprotéines › Globines › Hémoglobines › Hémoglobines anormales › Hémoglobine S › PF-07059013: A Noncovalent Modulator of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › PF-07059013: A Noncovalent Modulator of...
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questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Quinoléines › PF-07059013: A Noncovalent Modulator of...