"目录号: HY-13701
Cell Cycle/DNA Damage-
Nelarabine (Arranon, 506U78)是嘌呤核苷酸类似物，为DNA合成抑制剂，对肿瘤细胞的IC50为0.067-2.15 μM，可作用于T细胞急性淋巴细胞白血病。
Nucleoside Antimetabolite/Analog
相关产品
5-Fluorouracil-Gemcitabine-5-Azacytidine-Cytarabine-Capecitabine-5-BrdU-Forodesine hydrochloride-Triciribine-Trifluorothymidine-Merimepodib-Raltitrexed-Floxuridine-Tipiracil hydrochloride-6-Mercaptopurine-Dacarbazine-
生物活性
Description
Nelarabine (Arranon, 506U78) is a purine nucleoside analog and DNA synthesis inhibitor with IC50 from 0.067-2.15 μM in tumor cells. Nelarabine is a chemotherapy drug used in T-cell acute lymphoblastic leukemia. IC50 Value: 0.44 uM (HSB2 cell lines); 1.24 μM(ALL-SIL cell lines); 2.15 μM(JURKAT cell lines); 0.067 uM (PER-255 cell lines) [1]Target: Nucleoside antimetabolite/analogin vitro: The IC50 of Nelarabine is 25-fold and 113-fold higher than ARAC in T- and B-lineage, respectively. T-ALL cells are eightfold more sensitive to Nelarabine than B-lineage but there is considerable overlap. The efficacy of NEL in T-lineage and B-lineage cell lines is 25-fold and 113-fold less than ARAC, respectively [1].in vivo: The median age was 34 years (range, 16-66 years); 32 (82%) patients were male. The rate of complete remission was 31% (95% confidence interval [CI], 17%, 48%) and the overall response rate was 41% (95% CI, 26%, 58%). The principal toxicity was grade 3 or 4 neutropenia and thrombocytopenia, occurring in 37% and 26% of patients, respectively [2]. Nelarabine has activity in T-cell malignancies, as evaluated in 2 Phase I and 5 Phase II studies. It received accelerated approval from the FDA based on the resuits of 2 Phase II trials, one in pediatric patients (PGAA 2001) and the other in adults (CALGB 19801)Toxicity: The principal toxicity was grade 3 or 4 neutropenia and thrombocytopenia, occurring in 37% and 26% of patients, respectively [2].Clinical trial: Drug Use Investigation for Arranon G (Nelarabine) Injection 250 mg.
Clinical Trial
NCT00004239
Alliance for Clinical Trials in Oncology-National Cancer Institute (NCI)
Chronic Myeloproliferative Disorders-Leukemia-Lymphoma-Multiple Myeloma and Plasma Cell Neoplasm-Myelodysplastic Syndromes
December 1999
Phase 1
NCT00004239
Alliance for Clinical Trials in Oncology-National Cancer Institute (NCI)
Chronic Myeloproliferative Disorders-Leukemia-Lymphoma-Multiple Myeloma and Plasma Cell Neoplasm-Myelodysplastic Syndromes
December 1999
Phase 1
NCT00004239
Alliance for Clinical Trials in Oncology-National Cancer Institute (NCI)
Chronic Myeloproliferative Disorders-Leukemia-Lymphoma-Multiple Myeloma and Plasma Cell Neoplasm-Myelodysplastic Syndromes
December 1999
Phase 1
NCT01094860
M.D. Anderson Cancer Center-GlaxoSmithKline
Leukemia
June 2010
Phase 1
NCT00866671
GlaxoSmithKline
Leukaemia, Lymphoblastic, Acute
February 2009
NCT01376115
Novartis Pharmaceuticals-Novartis
Cancer
January 18, 2008
NCT02763384
Washington University School of Medicine
T-Acute Lymphoblastic Leukemia-Adult T Lymphoblastic Lymphoma
December 2, 2016
Phase 2
NCT00005080
National Cancer Institute (NCI)
Anaplastic Large Cell Lymphoma-Angioimmunoblastic T-cell Lymphoma-Recurrent Adult T-cell Leukemia/Lymphoma-Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma-Recurrent Mycosis Fungoides/Sezary Syndrome-Small Intestine Lymphoma-Stage I Cutaneous T-cell Non-Hodgkin Lymphoma-Stage I Mycosis Fungoides/Sezary Syndrome-Stage II Cutaneous T-cell Non-Hodgkin Lymphoma-Stage II Mycosis Fungoides/Sezary Syndrome-Stage III Cutaneous T-cell Non-Hodgkin Lymphoma-Stage III Mycosis Fungoides/Sezary Syndrome-Stage
May 2000
Phase 2
NCT00684619
Johann Wolfgang Goethe University Hospital
T-ALL, T-NHL (Lymphoblastic)
June 2003
Phase 2
NCT00981799
Therapeutic Advances in Childhood Leukemia Consortium-GlaxoSmithKline-Novartis
Relapsed T-Cell Acute Lymphoblastic Leukemia-Relapsed T-Cell Lymphoblastic Lymphoma
June 2010
Phase 1-Phase 2
NCT00501826
M.D. Anderson Cancer Center-Novartis
Leukemia-Lymphoblastic Lymphoma-Leukemia, Lymphoblastic, Acute
July 11, 2007
Phase 2
NCT00005982
National Cancer Institute (NCI)
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma-Recurrent Mycosis Fungoides/Sezary Syndrome
April 2000
Phase 2
NCT00005950
National Cancer Institute (NCI)
Angioimmunoblastic T-cell Lymphoma-Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue-Nodal Marginal Zone B-cell Lymphoma-Recurrent Adult T-cell Leukemia/Lymphoma-Recurrent Grade 1 Follicular Lymphoma-Recurrent Grade 2 Follicular Lymphoma-Recurrent Marginal Zone Lymphoma-Recurrent Small Lymphocytic Lymphoma-Splenic Marginal Zone Lymphoma-Waldenström Macroglobulinemia
April 2000
Phase 2
NCT00406757
GlaxoSmithKline
Leukaemia, Lymphoblastic, Acute and Lymphoma, Lymphoblastic-Lymphoblastic Lymphoma-Acute Lymphoblastic Leukemia
August 2006
Phase 1
NCT02619630
Assistance Publique - Hôpitaux de Paris
T-cell Adult Acute Lymphoblastic Leukemia
December 2015
Phase 2
NCT00003545
National Cancer Institute (NCI)-Southwest Oncology Group
Leukemia-Lymphoma
August 1998
Phase 2
NCT00003837
National Cancer Institute (NCI)
Leukemia-Lymphoma
September 1999
NCT00006020
Southwest Oncology Group-National Cancer Institute (NCI)
Leukemia
July 2000
Phase 2
NCT00003635
GlaxoSmithKline-National Cancer Institute (NCI)
Leukemia
January 1999
Phase 2
NCT00002970
National Cancer Institute (NCI)-Children's Cancer Group
Recurrent Childhood Acute Lymphoblastic Leukemia-Recurrent Childhood Lymphoblastic Lymphoma-T-cell Childhood Acute Lymphoblastic Leukemia
June 1997
Phase 2
NCT02881086
Johann Wolfgang Goethe University Hospital
Acute Lymphoblastic Leukemia-Lymphoblastic Lymphoma
August 2016
Phase 3
NCT01085617
University College London Hospitals-National Cancer Institute (NCI)
Leukemia-Mucositis-Oral Complications
January 2010
Phase 3
NCT00408005
National Cancer Institute (NCI)
Adult T Acute Lymphoblastic Leukemia-Childhood T Acute Lymphoblastic Leukemia-Stage II Adult T-Cell Leukemia/Lymphoma-Stage II Childhood Lymphoblastic Lymphoma-Stage II Contiguous Adult Lymphoblastic Lymphoma-Stage II Non-Contiguous Adult Lymphoblastic Lymphoma-Stage III Adult Lymphoblastic Lymphoma-Stage III Adult T-Cell Leukemia/Lymphoma-Stage III Childhood Lymphoblastic Lymphoma-Stage IV Adult Lymphoblastic Lymphoma-Stage IV Adult T-Cell Leukemia/Lymphoma-Stage IV Childhood Lymphoblastic Lymp
January 22, 2007
Phase 3
NCT00016302
National Cancer Institute (NCI)
T-cell Childhood Acute Lymphoblastic Leukemia-Untreated Childhood Acute Lymphoblastic Leukemia
April 2001
NCT02518750
St. Jude Children's Research Hospital-Novartis Pharmaceuticals-Spectrum Pharmaceuticals, Inc
Acute Lymphoblastic Leukemia-Lymphoma, Non-Hodgkin's-Leukemia, T-Cell-Leukemia, B-Cell
November 23, 2016
Phase 2
NCT03020030
Dana-Farber Cancer Institute-Baxalta US Inc.
Acute Lymphoblastic Leukemia, Pediatric
January 2017
Phase 3
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References
[1].Beesley AH, et al. In vitro cytotoxicity of nelarabine, clofarabine and flavopiridol in paediatric acute lymphoblastic leukaemia. Br J Haematol. 2007 Apr;137(2):109-16.
[2].DeAngelo DJ, et al. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood. 2007 Jun 15;109(12):5136-42.