生物活性

• 描述The DNA methyltransferase (DNMT) family are enzymes that can mediate the DNA methylation. Inhibiting the DNMTs have shown particular promise in reducing the formation of tumors^[5]. The decitabine is a potent inhibitor of the DNA methylation with IC50 value of 100 and 10 ng/ml for 72 and 96h of exposure on both HL-60 and KG1a leukemic cells^[6]. The human aortic smooth muscle cells (HASMCs) were treated with decitabine for 48 hours. The DNMT1 expression measured by western blotting assay in the nuclear fraction was reduced by the decitabine. The expression of the osteogenic genes ALP, Max2, BMP2, Pit-1, SM22 and -SMA in HASMCs measured by RT-qPCR was increased by decitabine^[7]. The hyperoxia-indued lung injury Sprague-Dawley rats were injected with decitabine at a dose of 0.5 mg/kg/day for 14 days. The survival rate of the treatment group was significantly higher than the hyperoxia group. The P16 methylation rate in the lung tissues measured by PCR was induced by the hyperoxia and the decitabine could effectively reverse the hypermethylation of P16^[8].
• 作用机制Decitabine could combine with DNA during DNA replication and form covalent complexes with the DNMT1. Therefore, the methyl transfer activity of the enzyme is inhibited^[8].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  A375	0.5 μM	Growth Inhibition Assay	1/5/8 d	inhibits proliferation and induces differentiation of melanoma cells	21796622
  A498	0.01-10μM	Apoptosis Assay	72 h	induces synergistic responses with romidepsin	22826467
  A549	5/10/20/50 μM	Apoptosis Assay	48 h	inhibits the cell viability	23582784

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• 动物研究
  剂量	Mice: 50 mg/kg - 150 mg/kg[3] (i.v.), 1 mg/kg - 32 mg/kg[3] (i.p.), 25 mg/kg[4] (p.o.)
  给药途径	i.v., i.p., p.o.
  动物药代数据	Animal Dogs[4] Dose 4 mg/kg Administration i.v. t1/2β 69 ± 4.5 min t1/2α 5.5 ± 0.9 min Vdβ 958 ± 164 ml/kg CL 6.6 ± 0.9 ml/min/kg Vdss 779 ± 102 ml/kg AUC0→∞ 478 ± 54 μg/ml/min K10 0.021 ± 0.004 min-1

• 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
  NCT02564536	Chronic Myelomonocytic Leukemi... more >>a Juvenile Myelomonocytic Leukemia Atypical Chronic Myeloid Leukemia Myeloproliferative Neoplasm Myelodysplastic Syndromes Myelofibrosis Collapse <<	Phase 1	Withdrawn(Lack of funding foll... more >>owing full FDA clinical hold) Collapse <<	June 30, 2020	-
  NCT01130506	Previously Treated Myelodyspla... more >>stic Syndrome Recurrent Adult Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia Secondary Acute Myeloid Leukemia Therapy-Related Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia Collapse <<	Phase 1	Completed	-	United States, Ohio ... more >> Ohio State University Comprehensive Cancer Center Columbus, Ohio, United States, 43210 United States, Texas M D Anderson Cancer Center Houston, Texas, United States, 77030 Collapse <<
  NCT03240211	PTCL CTCL	Phase 1	Recruiting	December 2020	United States, New York ... more >> 51 West 51st Street, Suite 200 Recruiting New York, New York, United States, 10019 Contact: Michelle Malanga    212-326-5731    mm4629@cumc.columbia.edu    Italy University of Bologna Not yet recruiting Bologna, Italy Principal Investigator: Pier Luigi Zinzani, MD, PhD          Korea, Republic of Samsung Medical Center Not yet recruiting Seoul, Korea, Republic of Principal Investigator: Won Seog Kim, MD, PhD Collapse <<

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