"目录号: HY-14660
Dabrafenib 是一种ATP竞争性的BRAF抑制剂，能够抑制 CRAF 和 BRAFV600E的活性，IC50值分别为 5 nM 和 0.6 nM。
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Sorafenib-Vemurafenib-PLX8394-Doramapimod-LGX818-Dabrafenib Mesylate-PLX-4720-LY3009120-PLX7904-GW 5074-MLN 2480-AZ 628-HG6-64-1-Ro 5126766-TAK-632-
生物活性
Description
Dabrafenib is an ATP-competitive inhibitor ofBRAFwithIC50s of 5 nM and 0.6 nM for CRAF and BRAFV600E, respectively.
IC50& Target
IC50: 0.6 nM (BRAFV600E), 5 nM (CRAF)[4]
In Vitro
Dabrafenib (GSK2118436, 1 μM) with 0.01 μM GSK1120212 inhibits more than 90% of cell growth in the NRAS mutant clones. GSK2118436 is sufficient to reduce S6P phosphorylation in A375[1]. Dabrafenib suppresses the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6[2]. Dabrafenib inhibits the release of HMGB1 and downregulates HMGB1-dependent inflammatory responses by enhancing the expressions of cell adhesion molecules (CAMs) in human endothelial cells[3].
In Vivo
Dabrafenib-treated females have mostly immature reproductive tracts with no evidence of ovulation, similar to age-matched controls; however, DAB-treated females have keratinized and histologically open vaginas[5].
Clinical Trial
University Medical Center Groningen
Melanoma
October 2016
Phase 1
Memorial Sloan Kettering Cancer Center-National Comprehensive Cancer Network-Novartis
Melanoma
September 2012
Phase 2
Melanoma Institute Australia
Melanoma
October 2014
Phase 2
University Hospital Tuebingen
Metastatic Melanoma (Carrying BRAF V600 Mutation)
January 2014
Phase 2
M.D. Anderson Cancer Center-Novartis Pharmaceuticals
Melanoma
October 2014
Phase 2
UNC Lineberger Comprehensive Cancer Center-GlaxoSmithKline
Stage III Melanoma-Stage IV Melanoma-Unresectable Melanoma-BRAF Mutant Melanoma
October 2012
Phase 2
University of California, San Francisco-GlaxoSmithKline
BRAFV600E Melanoma Patients
April 2013
Phase 2
Stanford University-National Cancer Institute (NCI)
Ameloblastoma-BRAF Gene Mutation
August 2017
Phase 2
Canadian Cancer Trials Group-Novartis
Melanoma-Brain Metastases
November 23, 2016
Phase 2
GlaxoSmithKline
Melanoma
May 2017
Phase 1
National Cancer Institute (NCI)
BRAF V600E Mutation Present-BRAF V600K Mutation Present-Metastatic Malignant Neoplasm in the Thyroid Gland-Recurrent Thyroid Gland Carcinoma-Unresectable Thyroid Gland Carcinoma
August 29, 2013
Phase 1
National Cancer Institute (NCI)-Glaxosmithkline Biologicals S.A.
BRAF Gene Mutation-Hepatic Complication-Renal Failure-Solid Neoplasm
August 23, 2013
Phase 1
GlaxoSmithKline
Melanoma and Brain Metastases
April 2014
Phase 2
Novartis Pharmaceuticals-Novartis
Non-Small-Cell Lung Cancer
October 31, 2017
Phase 2
Universitair Ziekenhuis Brussel
Malignant Melanoma
October 2014
Phase 2
GlaxoSmithKline
Cancer
March 12, 2014
Phase 2
University of Utah
Stage III or IV Melanoma
December 2014
Phase 1
GlaxoSmithKline
Solid Tumours
February 12, 2013
Phase 1
GlaxoSmithKline
Neoplasms, Brain
February 27, 2013
Phase 1
GlaxoSmithKline
Melanoma
May 2012
Phase 3
GlaxoSmithKline
Cancer
March 18, 2014
Phase 2
National Cancer Institute (NCI)
BRAF V600E Mutation Present-BRAF V600K Mutation Present-Metastatic Malignant Solid Neoplasm-Recurrent Malignant Solid Neoplasm-Recurrent Melanoma-Stage III Skin Melanoma-Stage IIIA Skin Melanoma-Stage IIIB Skin Melanoma-Stage IIIC Skin Melanoma-Stage IV Skin Melanoma-Unresectable Solid Neoplasm
May 29, 2014
Phase 1
Massachusetts General Hospital-Novartis-Multiple Myeloma Research Consortium
Multiple Myeloma
May 2017
Phase 1
GlaxoSmithKline
Melanoma
January 8, 2013
Phase 3
GlaxoSmithKline
Cancer
December 20, 2013
Phase 1
National Cancer Institute (NCI)
Metastatic Melanoma-Recurrent Melanoma-Solid Neoplasm-Stage IIIA Skin Melanoma-Stage IIIB Skin Melanoma-Stage IIIC Skin Melanoma-Stage IV Skin Melanoma
October 25, 2013
Phase 1-Phase 2
Manisha Shah-National Comprehensive Cancer Network-Ohio State University Comprehensive Cancer Center
Unspecified Adult Solid Tumor, Protocol Specific
November 19, 2012
Phase 1
Novartis Pharmaceuticals-Novartis
Anaplastic Astrocytoma-Glioblastoma-Giant Cell Glioblastoma-Gliosarcoma-Anaplastic Oligodendroglioma-Anaplastic Oligoastrocytoma-Anaplastic Ependymoma-Choroid Plexus Carcinoma-Anaplastic Ganglioglioma-Pineal Parenchymal Tumor-Pineoblastoma-Medulloblastoma-PNET-Rhabdoid Tumor-Perineurioma-MPNST-Malignant Meningloma-Anaplastic Hemangiopericytoma
October 30, 2017
Phase 2
James Graham Brown Cancer Center-University of Louisville
Melanoma
September 2014
Phase 1-Phase 2
Novartis Pharmaceuticals-Novartis
Renal Impairment
December 19, 2016
Phase 1
Novartis Pharmaceuticals-Novartis
Hepatic Impairment
December 21, 2016
Phase 1
Manisha Shah-National Comprehensive Cancer Network-Ohio State University Comprehensive Cancer Center
Follicular Thyroid Cancer-Insular Thyroid Cancer-Papillary Thyroid Cancer-Recurrent Thyroid Cancer
November 7, 2012
Phase 2
GlaxoSmithKline
Cancer
June 2011
Phase 2
GlaxoSmithKline
Melanoma
November 2013
Phase 2
Memorial Sloan Kettering Cancer Center-Massachusetts General Hospital-Weill Medical College of Cornell University
Melanoma
January 2017
Phase 1
University of Pittsburgh-Bristol-Myers Squibb
Metastatic Melanoma
August 2015
Phase 1
National Cancer Institute (NCI)-GlaxoSmithKline-Novartis Pharmaceuticals
Adult Solid Neoplasm-Recurrent Colon Carcinoma-Recurrent Melanoma-Recurrent Ovarian Carcinoma-Stage IIIC Colon Cancer-Stage IIIC Ovarian Cancer-Stage IIIC Skin Melanoma-Stage IV Skin Melanoma
July 19, 2013
Phase 1-Phase 2
M.D. Anderson Cancer Center-Bristol-Myers Squibb
Melanoma
December 2016
Phase 2
National Cancer Institute (NCI)
BRAF V600E Mutation Present-BRAF V600K Mutation Present-Recurrent Melanoma-Stage III Skin Melanoma-Stage IIIA Skin Melanoma-Stage IIIB Skin Melanoma-Stage IIIC Skin Melanoma-Stage IV Skin Melanoma
July 22, 2014
Phase 2
National Human Genome Research Institute (NHGRI)-National Institutes of Health Clinical Center (CC)
BRAF V600E Mutation
October 14, 2014
Phase 2
Novartis Pharmaceuticals-Novartis
Melanoma
February 17, 2017
Phase 3
Craig L Slingluff, Jr-National Cancer Institute (NCI)-University of Virginia
Melanoma
April 2016
Phase 1-Phase 2
GlaxoSmithKline
Cancer
January 15, 2015
Phase 1
GlaxoSmithKline
Melanoma and Brain Metastases
February 21, 2014
Phase 2
Vanderbilt-Ingram Cancer Center-National Cancer Institute (NCI)-National Comprehensive Cancer Network
Recurrent Melanoma-Stage IIB Melanoma (Locally Advanced)-Stage IIC Melanoma (Locally Advanced)-Stage IIIA Melanoma-Stage IIIB Melanoma-Stage IIIC Melanoma-Stage IV Melanoma (Limited, Resectable)
January 2013
Phase 2
