"目录号: HY-13756
Autophagy-
Tacrolimus 结合到FK506 结合蛋白(FKBP)形成复合体，复合体抑制钙调磷酸酶 (PP2B)。Tacrolimus 是一种 mTOR 非依赖性的自噬诱导剂。
Autophagy
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生物活性
Description
Tacrolimus binds toFK506 binding protein(FKBP). This complex inhibits calcineurin phosphatase (PP2B). Tacrolimus is a mTOR-independentautophagyinducer.
IC50& Target
PP2B (calcineurin phosphatase)[1]
Autophagy inducer[2]
In Vitro
Tacrolimus (FK506) inhibits calcium-dependent events, such as IL-2 gene transcription, NO synthase activation, cell degranulation, and apoptosis. Tacrolimus also potentiates the actions of glucocorticoids and progesterone by binding to FKBPs contained within the hormone receptor complex, preventing degradation. The agent may enhance expression of the TGFβ-1 gene in a fashion analogous to that demonstrated for CsA. T cell proliferation in response to ligation of the T cell receptor is inhibited by Tacrolimus[1]. Tacrolimus (FK506) is a powerful immunosuppressive drug widely used to prevent organ rejection after transplantation. Tacrolimus inhibit other calcineurin-dependent transcription factors including the ubiquitously expressed cAMP response element-binding protein (CREB). Tacrolimus inhibit CREB transcriptional activity at the coactivator level. The depolarization-induced transcriptional activity of the CBP C-terminus is enhanced by overexpression of calcineurin and is inhibited by Tacrolimus in a concentration-dependent manner with IC50of 1 nM consistent with IC50for inhibition of calcineurin[3].
In Vivo
In the pleurisy induced by carrageenan, Tacrolimus (1 mg/kg, i.p.) and Dexamethasone (0.5 mg/kg, i.p.) administered 0.5 h before causes a significant decrease in leukocytes, neutrophils and exudation (P<0.01). Under the same conditions, Tacrolimus and Dexamethasone do not modify the blood's white or red cells (P>0.05). Tacrolimus shows a long lasting antiinflammatory effect, inhibiting leukocytes and neutrophils for up to 24 h (P<0.01), whereas the inhibition of exudation is less marked (up to 2 h) (P<0.01). These drugs caused a marked reduction in MPO activity, as well as IL-1β and TNFα levels (P<0.01), but only Tacrolimus inhibits ADA activity (P<0.01). Tacrolimus significantly inhibits cell migration induces by either bradykinin, histamine or substance P (P<0.05)[4].
Clinical Trial
NCT00578903
Baylor College of Medicine-The Methodist Hospital System-Texas Children's Hospital-Center for Cell and Gene Therapy, Baylor College of Medicine
Aplastic Anemia
February 2002
Phase 2
NCT00579111
Baylor College of Medicine-Center for Cell and Gene Therapy, Baylor College of Medicine-The Methodist Hospital System
Myelodysplastic and Myeloproliferative Disorders-Acute Myelogenous Leukemia-Acute Lymphoblastic Leukemia-Chronic Myelogenous Leukemia-Multiple Myeloma-Plasma Cell Dyscrasia-Lymphoproliferative Disorders-Hematologic Diseases
June 2007
Phase 1-Phase 2
NCT00302549
Nanjing University School of Medicine-Sun Yat-sen University
Lupus Nephritis
May 2004
NCT00567918
Astellas Pharma Inc
Keratoconjunctivitis-Conjunctivitis
May 2004
Phase 3
NCT02118896
Astellas Pharma Europe Ltd.-Astellas Pharma Inc
Kidney Transplantation-Liver Transplantation-Heart Transplantation
January 2003
Phase 3
NCT00619398
Astellas Pharma Inc
Liver Transplantation
January 2008
Phase 3
NCT01451489
Nanjing University School of Medicine
FSGS
October 13, 2011
NCT01647945
Edda Spiekerkoetter-Stanford University
Pulmonary Arterial Hypertension
July 2012
Phase 2
NCT00956059
Health Science Center of Xi’an Jiaotong University
Focal Segmental Glomerulosclerosis
September 2009
NCT00567762
Astellas Pharma Inc
Keratoconjunctivitis-Conjunctivitis
February 2004
Phase 3
NCT00909571
Astellas Pharma Inc-Astellas Pharma Korea, Inc.
Liver Transplantation
April 2009
Phase 3
NCT00931255
University of Maryland-Wyeth is now a wholly owned subsidiary of Pfizer
Kidney Transplant-Delayed Graft Function-Slow Graft Function-defined at Creatinine >= 3.0 by Post-op Day 5 Without Requiring Dialysis
April 2009
Phase 4
NCT00615667
Sun Yat-sen University
Kidney Diseases-Nephrotic Syndrome-Tacrolimus
June 2006
Phase 3
NCT00481819
Astellas Pharma Inc
Kidney Transplantation
July 2007
Phase 3
NCT02752529
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Cirrhosis, Liver
March 2016
NCT00463723
University Hospital Freiburg-Sucampo Pharmaceuticals, Inc.
Penetrating Keratoplasty
Phase 2-Phase 3
NCT01161459
Zhi-Hong Liu, M.D.-Nanjing University School of Medicine
Idiopathic Membranous Nephropathy
June 2010
NCT00615173
Sun Yat-sen University
Kidney Diseases-Lupus Nephritis-Tacrolimus-Induction Phase-Maintenance Phase
July 2006
Phase 3
NCT00965094
Novartis Pharmaceuticals-Novartis
Chronic Renal Failure
December 2009
Phase 4
NCT00056979
Baylor College of Medicine-Texas Children's Hospital-The Methodist Hospital System
Inherited Metabolic Storage Diseases
June 2002
Phase 1-Phase 2
NCT00034528
National Institute of Allergy and Infectious Diseases (NIAID)
Hemoglobinopathies-Anemia, Sickle Cell-Hemoglobin SC Disease-Thalassemia-Thalassemia Major
September 2001
Phase 2
NCT00177099
Hordinsky, Maria K., MD-University of Minnesota - Clinical and Translational Science Institute
Alopecia
July 2003
Phase 1
NCT00058825
Baylor College of Medicine-Texas Children's Hospital-The Methodist Hospital System
Hematologic Malignancies
August 2000
Phase 1-Phase 2
NCT00056966
Baylor College of Medicine-Texas Children's Hospital-The Methodist Hospital System-Center for Cell and Gene Therapy, Baylor College of Medicine
Hematologic Malignancy
November 2002
Phase 1-Phase 2
NCT00048399
Baylor College of Medicine-The Methodist Hospital System-Texas Children's Hospital
Graft Failure
December 2000
Phase 1-Phase 2
NCT00040417
Baylor College of Medicine-Texas Children's Hospital-The Methodist Hospital System
Sickle Cell Anemia-Hemoglobinopathy-Thalassemia
August 2000
Phase 2
NCT00302523
Nanjing University School of Medicine
Idiopathic Membranous Nephropathy
March 2006
NCT00302536
Nanjing University School of Medicine
Focal Glomerulosclerosis
March 2006
NCT02608606
Pontificia Universidad Catolica de Chile
Evidence of Liver Transplantation-Effects of Immunosuppressant Therapy
March 2015
NCT02794610
The Eye Center and The Eye Foundation for Research in Ophthalmology
Ocular Penetration of Topical Tacrolimus
May 2016
NCT02444143
University of Illinois at Chicago-Astellas Pharma US, Inc.
Kidney Transplantation
May 2015
Phase 4
NCT01131988
Dr. Reddy's Laboratories Limited
Healthy
January 2008
Phase 1
NCT02456025
The Eye Center and The Eye Foundation for Research in Ophthalmology
Vernal Keratoconjunctivitis
April 2013
Phase 4
NCT01132027
Dr. Reddy's Laboratories Limited
Healthy
January 2008
Phase 1
NCT03020589
University of North Carolina, Chapel Hill
Renal Transplant
January 2017
Phase 4
NCT00935298
The Second Artillery General Hospital-Capital Medical University-Shanghai Changzheng Hospital-Pharmacology Research Institute-Air Force General Hospital of the PLA-Health Department of General Logistics
Renal Transplantation
July 2009
Phase 4
NCT01655563
The Hospital for Sick Children
Heart Transplantation-Liver Transplantation-Kidney Transplantation
September 2011
Phase 2
NCT00492661
Janssen-Cilag Pty Ltd
Renal Transplantion-Kidney Transplantion
July 2007
Phase 4
NCT02014103
University of Cincinnati-University of Colorado, Denver-Children's Hospital Medical Center, Cincinnati
Complication of Transplant
March 2015
Phase 4
NCT00843856
Imperial College Healthcare NHS Trust
Glomerulonephritis, Membranous
February 2009
Phase 4
NCT02837978
Qiang Shu-Qilu Hospital of Shandong University
Arthritis, Rheumatoid
January 2015
Phase 4
NCT02743247
Seoul National University Hospital-Ministry of Food and Drug Safety, Korea
Healthy Volunteers
October 2015
Phase 1
NCT00950391
Washington University School of Medicine
Peripheral Nerve Injury
August 2010
Phase 1-Phase 2
NCT00535691
Astellas Pharma Inc