生物活性

• 描述Adenosine deaminase (ADA) is a critical enzyme that mediates the intracellular level of adenosine via the irreversible deamination of adenosine to inosine and thereby degrades purine and deoxypurine nucleotides. Pentostatin irreversibly inhibits ADA with a K_i value of 0.09 nM, which results in the accumulation of triphosphate metabolites in the cytosol and impedes DNA synthesis in dividing cells^[3]. The treatment with pentostatin (1 – 100M) in combination with 2′-deoxyadenosine inhibited the colony growth in T-cells lacking surface CD26/ADA complex expression in a dose-dependent manner. Pentostatin at 0.5μM reduced the cell survival to 50% of control in KE-37 and FRO cell lines. It also led to a 50% survival reduction versus control at 1.0 and 11μM in Jurkat cell line and CEM cell line, respectively. Incubation of T-cell lines with pentostatin (25μM) and 2′-deoxyadenosine (25μM) increased the percentage of apoptotic nuclei and the number of apoptotic cells detected in the sub-G₁ areas compared to the control group^[4]. In nude mice inoculated with human monocytoid U937 cells, injection of pentostatin (0.25 and 2.5mg/kg, 3 times per week) significantly prolonged the mean survival rate (28.6 and 31.2 days, respectively) in comparison to the controls (21.5 days)^[5].

• 动物研究
  剂量	Rat: 0.1 mg/kg, 1 mg/kg[3] (s.c.) Dog: 0.2 mg/kg[4] (i.v.) Mice: 2 mg/kg[2] (i.p.)
  给药途径	s.c., i.v., i.p.

• 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
  NCT02551718	Acute Leukemia of Ambiguous Li... more >>neage Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia Refractory Adult Acute Lymphoblastic Leukemia Refractory Childhood Acute Lymphoblastic Leukemia Collapse <<	Not Applicable	Recruiting	-	United States, Washington ... more >> Fred Hutch/University of Washington Cancer Consortium Recruiting Seattle, Washington, United States, 98109 Contact: Pamela S. Becker    206-616-1589    pbecker@u.washington.edu    Principal Investigator: Pamela S. Becker Collapse <<
  NCT03663933	Lymphoproliferative Disorders ... more >> Autoimmune Lymphoproliferative Primary T-cell Immunodeficiency Disorders Immune System Diseases Common Variable Immunodeficiency Collapse <<	Phase 2	Recruiting	May 1, 2024	United States, Maryland ... more >> National Institutes of Health Clinical Center Recruiting Bethesda, Maryland, United States, 20892 Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937 Collapse <<
  NCT01862965	Chronic Graft-versus-host Dise... more >>ase Collapse <<	Phase 2	Active, not recruiting	June 2018	Germany ... more >> Universitätsklinikum Hamburg-Eppendorf Hamburg, Germany, 20246 Universitätsklinikum Jena Jena, Germany, 07743 Universitätsmedizin der Johannes Gutenberg-Universität Mainz Mainz, Germany, 55101 Klinikum der Universität Regensburg Regensburg, Germany, 93053 Universitätsklinikum Ulm Ulm, Germany, 89081 Deutsche Klinik fuer Diagnostik GmbH Wiesbaden, Germany, 65191 Collapse <<

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• 参考文献

• [1] Bethge WA, Kerbauy FR, et al. Extracorporeal photopheresis combined with pentostatin in the conditioning regimen for canine hematopoietic cell transplantation does not prevent GVHD. Bone Marrow Transplant. 2014 Sep;49(9):1198-204.

  [2] Dalla Rosa L, da Silva AS, et al. Cordycepin (3'-deoxyadenosine) pentostatin (deoxycoformycin) combination treatment of mice experimentally infected with Trypanosoma evansi. Parasitology. 2013 Apr;140(5):663-71.

  [3] Shewach DS, Krawczyk SH, Acevedo OL, Townsend LB. Inhibition of adenosine deaminase by azapurine ribonucleosides. Biochem Pharmacol. 1992 Nov 3;44(9):1697-700. doi: 10.1016/0006-2952(92)90061-m. PMID: 1449528.

  [4] Aldinucci D, Poletto D, Lorenzon D, Nanni P, Degan M, Olivo K, Rapanà B, Pinto A, Gattei V. CD26 expression correlates with a reduced sensitivity to 2'-deoxycoformycin-induced growth inhibition and apoptosis in T-cell leukemia/lymphomas. Clin Cancer Res. 2004 Jan 15;10(2):508-20. doi: 10.1158/1078-0432.ccr-0755-03. PMID: 14760072.

  [5] Niitsu N, Yamamoto-Yamaguchi Y, Kasukabe T, Okabe-Kado J, Umeda M, Honma Y. Antileukemic efficacy of 2-deoxycoformycin in monocytic leukemia cells. Blood. 2000 Aug 15;96(4):1512-6. PMID: 10942399.

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