"目录号: HY-14649
Metabolic Enzyme/ProteaseCell Cycle/DNA DamageNF-κB-
Retinoic acid 是一种天然的RAR/RXR核受体激动剂。Retinoic acid 也结合到PPARβ/δ，Kd为 17 nM。
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生物活性
Description
Retinoic acid is a natural agonist ofRAR/RXRnuclear receptors. Retinoic acid also bind toPPARβ/δ, withKdof 17 nM.
IC50& Target
RAR/RXR[1]
Kd: 17 nM (PPARβ/δ), 103 nM (PPARα), 178 (PPARγ)[2]
In Vitro
Retinoic acid (All-trans-retinoic acid, ATRA) is a highly potent derivative of vitamin A that is required for virtually all essential physiological processes and functions because of its involvement in transcriptional regulation of over 530 different genes. Retinoic acid exerts its actions by serving as an activating ligand of nuclear retinoic acid receptors (RARα-γ), which form heterodimers with retinoid X receptors (RXRα-γ)[1]. Retinoic acid (RA) bound to PPARα and PPARγ with a low affinity demonstrated by Kdvalues of 100-200 nM. In contrast, Retinoic acid associates with PPARβ/δ with a Kdof 17 nM, revealing both high affinity and isotype selectivity[2]. Undifferentiated P19 cells express the Retinoic acid (RA) receptors RARα, RARβ, RARγ, and PPARβ/δ, as well as the Retinoic acid -binding proteins CRABP-II and FABP5. Induction of differentiation by treatment of cells with Retinoic acid results in transient up-regulation of CRABP-II and down-regulation of FABP5 that are observed at the level of both the respective proteins and mRNAs. Following the initial decrease, the level of both FABP5 protein and mRNA increases to attain a 2-2.5-fold higher level in mature neurons as compared with undifferentiated P19 cells. Induction of differentiation does not markedly affect the levels of either RARα or PPARβ/δ. The level of RARγ mRNA decreases by about 5-fold by day 4 and remained low in mature neurons[3]. Retinoic acid (RA) is a morphogen derived from retinol (vitamin A) that plays important roles in cell growth, differentiation, and organogenesis. The Retinoic acid interacts with retinoic acid receptor (RAR) and retinoic acid X receptor (RXR) which then regulate the target gene expression[4].
Clinical Trial
University of Colorado, Denver-Merck Sharp & Dohme Corp.
Stage IV Melanoma-Stage III Melanoma-Advanced Melanoma
August 2017
Phase 1-Phase 2
University of Iowa-Molecular Insight Pharmaceuticals, Inc.
Neuroblastoma-Neuroendocrine Tumor
June 2009
Phase 2
University Hospital, Gentofte, Copenhagen
Hepatic Insufficiency
December 2010
M.D. Anderson Cancer Center-Celgene Corporation
Myeloma
December 2013
Phase 1
M.D. Anderson Cancer Center-AstraZeneca
Neuroblastoma
September 2007
Phase 1
University of Colorado, Denver
Melanoma
December 17, 2015
Phase 2
University of Washington
Male Infertility-Klinefelter's Syndrome-Y-chromosome Microdeletions
August 2014
Phase 2
University of North Carolina, Chapel Hill-National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
January 2012
Phase 2
New York University School of Medicine-Children's Hospitals and Clinics of Minnesota-Schneider Children's Hospital
Brain Tumors
October 2005
Phase 2
Sun Yat-sen University
Hypercholesterolemia
November 2014
Early Phase 1
Memorial Sloan Kettering Cancer Center
Neuroblastoma
August 2010
Phase 2
Yale University-Mayo Clinic
Cholangitis, Sclerosing
October 2011
Phase 1
University of Colorado, Denver
Drug Toxicity-Lung Cancer
January 1993
Phase 2
National Cancer Institute (NCI)-National Institutes of Health Clinical Center (CC)
Breast Cancer-Breast Neoplasm
May 1996
Phase 1
Memorial Sloan Kettering Cancer Center
Neuroblastoma
August 2010
Phase 2
Dana-Farber Cancer Institute-Brigham and Women's Hospital
Acute Myelogenous Leukemia-Myelodysplastic Syndrome
May 1997
Phase 2
Memorial Sloan Kettering Cancer Center
Neuroblastoma
August 2010
Phase 2
National Cancer Institute (NCI)-National Institutes of Health Clinical Center (CC)
Nephroblastoma-Neuroblastoma
July 1996
Phase 2
M.D. Anderson Cancer Center-Celgene Corporation
Myelodysplastic Syndrome-Acute Myelogenous Leukemia
July 2005
Phase 1
National Cancer Institute (NCI)-National Institutes of Health Clinical Center (CC)
HIV Infections-Immunologic Deficiency Syndromes-Lymphoproliferative Disorders
June 1995
Phase 2
University of Pittsburgh
Acute Myelogenous Leukemia-Myelodysplastic Syndrome
April 2011
Phase 1
M.D. Anderson Cancer Center
Acute Promyelocytic Leukemia
December 2006
Phase 2
M.D. Anderson Cancer Center-Celgene Corporation
Myelodysplastic Syndrome-Acute Myelogenous Leukemia
July 2005
Phase 2
H. Lee Moffitt Cancer Center and Research Institute
Small Cell Lung Cancer
October 2, 2007
Phase 2
Peking University People's Hospital-Beijing Municipal Science & Technology Commission-Beijing Hospital-Qilu Hospital of Shandong University-Navy General Hospital, Beijing-Beijing Tongren Hospital
Autoimmune Thrombocytopenia
June 1, 2012
Phase 2
James Graham Brown Cancer Center-University of Louisville
Cervical Cancer
October 2007
Phase 2
United Therapeutics
Primary Refractory Neuroblastoma
August 2009
Phase 2
Assistance Publique - Hôpitaux de Paris
Acute Myelogenous Leukaemia (AML)-Myelodysplastic Syndrome (MDS)
July 2006
Phase 2
Imago BioSciences,Inc.
Acute Myeloid Leukemia-Myelodysplastic Syndrome
October 2016
Phase 1
University of Ulm
Acute Myeloid Leukemia
June 2004
Phase 3
University of Ulm-German Federal Ministry of Education and Research
Acute Myeloid Leukemia (AML)
March 2011
Phase 3
University of Ulm
Acute Myeloid Leukemia
July 2004
Phase 2-Phase 3
Ulrike Kohlweyer-University Hospital Freiburg
Acute Myeloid Leukemia-Myelodysplastic Syndrome
May 2015
Phase 1-Phase 2
VU University Medical Center-EMC Rotterdam-UMC Utrecht-Vejle Hospital and University of Southern Denmark-Department of Medical Sciences, University of Torino
Multiple Myeloma
August 2016
Phase 1-Phase 2
National Heart, Lung, and Blood Institute (NHLBI)
Emphysema-Lung Diseases-Lung Diseases, Obstructive-Chronic Obstructive Pulmonary Disease
September 1999
Phase 2
Washington University School of Medicine
Leukemia, Myeloid, Acute
November 2010
Phase 1
Eastern Cooperative Oncology Group-National Cancer Institute (NCI)
Lung Cancer
February 2004
Phase 2
Gruppo Italiano Malattie EMatologiche dell'Adulto
Leukemia
October 1993
University of Bergen
Acute Myelogenous Leukemia
September 2009
Phase 1-Phase 2
H. Lee Moffitt Cancer Center and Research Institute-National Cancer Institute (NCI)-National Institutes of Health (NIH)
Lung Cancer
October 2006
Phase 2
First Affiliated Hospital Xi'an Jiaotong University-Tang-Du Hospital
Acute Promyelocytic Leukemia
September 2016
Phase 3
University of Bergen
Acute Myelogenous Leukemia
November 2004
Phase 1-Phase 2
St. Jude Children's Research Hospital-AstraZeneca-National Institutes of Health (NIH)
Neuroblastoma
August 2005
Phase 2
University of Cologne
Neuroblastoma
November 2015
Phase 2
