生物活性

• 描述Fludarabine Phosphate is the phosphate form of Fludarabine. Fludarabine (2-F-ARAA, 2-fluoro ARA-A) is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia (see https://www.fda.gov/) for targeting on DNA synthesis. It can also work as an inhibitor of stat1 activation. The mechanism of Fludarabine action against to DNA synthesis is similar to other nucleotide analogues. Fludarabine can be phosphorylated to form as the Fludarabine triphosphate and then compete with natural nucleotides to inhibit DNA polymeraseα and incorporate into DNA strand. It can also act on ribonucleotide reductase and thus deplete the dATP pool. Fludarabine can also cause a specific depletion of STAT1, but not of other STATs, as well as cytokine-induced activation of STAT1 and STAT1-dependent gene transcription in lymphocytes.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  HL60 cells	-	Proliferation assay	48 h	Antiproliferative activity against human HL60 cells assessed as cell growth inhibition after 48 hrs by MTT assay, IC50=0.09 μM	25960323
  K562 cells	-	Proliferation assay	48 h	Antiproliferative activity against human K562 cells assessed as cell growth inhibition after 48 hrs by MTT assay, IC50=0.4 μM	25960323
  KG1 cells	-	Proliferation assay	48 h	Antiproliferative activity against human KG1 cells assessed as cell growth inhibition after 48 hrs by MTT assay, IC50=0.15 μM	25960323

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• 动物研究
  剂量	Mice: 0.3 mg/kg - 0.8 mg/kg[3] (i.p.) Rat: 0.75 mg/kg - 60 mg/kg[4] (i.p.); 20 mg/kg, 75 mg/kg[5] (i.g.)
  给药途径	i.p., i.g.
  动物药代数据	Animal Rats[5] Dogs[5] Dose 20 mg/kg 86.7 mg/m2 Administration i.v. or i.g. i.v. or p.o. F 71.3% (plasma) 100.8 ± 15.4% (p.o.) V 3.20 L/kg (i.v.) T1/2 3.40 h (i.v.) 2.68 h (i.g.) 1.6 - 2.3 h (i.v.) 1.5 - 2.5 h (p.o.) Tmax 0.25 h (i.v.) 1.0 h (i.g.) 0.07 h (i.v.) 0.6 h (p.o.) CL 10.8 ml/min/kg (i.v.) 89 ± 14 ml/min/m2 (i.v.) Cmax 21.9 μM (i.v.) 8.21 μM (i.g.) 20.3 ± 1.0 μM (i.v.) 15.4 ± 3.8 μM (p.o.) AUC 84.2 μM·h (i.v.) 59.9 μM·h (i.g.) 46.2 ± 7.7 μM·h/ml (i.v.) 46.8 ± 11.9 μM·h/ml (p.o.)

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01056614	Accelerated Phase Chronic Myel... more >>ogenous Leukemia Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Blastic Phase Chronic Myelogenous Leukemia Childhood Acute Myeloid Leukemia in Remission Childhood Chronic Myelogenous Leukemia Childhood Myelodysplastic Syndromes Chronic Phase Chronic Myelogenous Leukemia de Novo Myelodysplastic Syndromes Hematopoietic/Lymphoid Cancer Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Previously Treated Myelodysplastic Syndromes Recurrent Adult Acute Myeloid Leukemia Recurrent Childhood Acute Myeloid Leukemia Relapsing Chronic Myelogenous Leukemia Collapse <<	Phase 2	Completed	-	United States, Washington ... more >> Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington, United States, 98109 Collapse <<
  NCT02333162	Previously Treated Myelodyspla... more >>stic Syndrome Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Hematologic Malignancy Collapse <<	Phase 1	Recruiting	December 2020	United States, Illinois ... more >> University of Chicago Comprehensive Cancer Center Recruiting Chicago, Illinois, United States, 60637 Contact: Hongtao Liu    773-834-0589    hliu2@medicine.bsd.uchicago.edu    Principal Investigator: Hongtao Liu Collapse <<
  NCT00086580	B-Cell Chronic Lymphocytic Leu... more >>kemia Collapse <<	Phase 3	Completed	-	-

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• 参考文献

• [1] Huang P, Chubb S, Plunkett W. Termination of DNA synthesis by 9-beta-D-arabinofuranosyl-2-fluoroadenine. A mechanism for cytotoxicity. J Biol Chem. 1990 Sep 25;265(27):16617-25.

  [2] Umbach GE, Hug V, et al. Responses of human bone marrow progenitor cells to fluoro-ara-AMP, homoharringtonine, and elliptinium. Invest New Drugs. 1984;2(3):263-5.

  [3] Weiss L, Abdul-Hai A, et al. Fludarabine in combination with cyclophosphamide decreases incidence of GVHD and maintains effective graft-versus-leukemia effect after allogeneic stem cell transplantation in murine lymphocytic leukemia. Bone Marrow Transplant. 2003 Jan;31(1):11-5.

  [4] Chlorambucil and fludarabine as a new pre-transplant conditioning for patients with chronic lymphocytic leukemia: results of in vivo experiments

  [5] OFORTA

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