生物活性

• 描述Gemcitabine (dFdCTP, LY-188011, NSC 613327, (+)-2'-Deoxy-2',2'-difluorocytidine) is a deoxycytidine analogue that has a spectrum of activity against solid tumors^[1]. Gemcitabine can inhibit DNA synthesis through a combination of two actions. The first, gemcitabine can inhibit ribonucleotide reductase (RR) and then cause the decrease of the deoxynucleotide pool sizes for DNA repair and synthesis^[2]. The second, gemcitabine inhibit DNA synthesis through competition with dCTP and incorporation into DNA^[3]. Gemcitabine can induce S-phase arrest and cell growth inhibition^[4].
• 作用机制Gemcitabine, as nucleoside analogue, can inhibit DNA synthesis through inhibition of ribonucleotide reductase and incorporation into DNA^[5].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  23132-87	-	Growth Inhibition Assay	-	IC50=43.05 nM	SANGER
  647-V	-	Growth Inhibition Assay	-	IC50=0.248 nM	SANGER
  697	-	Growth Inhibition Assay	-	IC50=6.25 nM	SANGER

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• 动物研究
  剂量	Mice (i.p.): min = 3.5 mg/kg, max = 240 mg/kg[6]
  给药途径	i.p.
  动物药代数据	Animal Rats[7] Dose 5 mg/kg Administration i.v. Cmax 8078 ± 4176 μg/l AUC0→∞ 25288 ± 11487 μg/l·h Vz 1.788 ± 1.265 l/kg AUC0→t 23480 ± 13061 μg/l·h CL 0.255 ± 0.161 l/h/kg t1/2z 5.04 ± 2.06 h

• 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
  NCT02240238	Solid Tumors	Phase 1 Phase 2	Recruiting	November 30, 2019	United States, California ... more >> California Cancer Associates for Research and Excellence Recruiting Encinitas, California, United States, 92024 UC San Diego Moores Cancer Center Recruiting La Jolla, California, United States, 92037 Pacific Hematology Oncology Associates Recruiting San Francisco, California, United States, 94115 United States, Illinois Northwestern University Feinberg School of Medicine Recruiting Chicago, Illinois, United States, 60611 United States, Massachusetts Tufts Medical Center Recruiting Boston, Massachusetts, United States, 02111 United States, North Carolina University of North Carolina at Chapel Hill Recruiting Chapel Hill, North Carolina, United States, 27599 United States, Ohio University Hospitals Case Medical Center Recruiting Cleveland, Ohio, United States, 44121 United States, Oklahoma University of Oklahoma Health Sciences Center Recruiting Oklahoma City, Oklahoma, United States, 73104 United States, Texas University of Texas Southwestern Medical Center Recruiting Dallas, Texas, United States, 75390 MD Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Bulgaria Multiprofile Hospital for Active Treatment Serdika EOOD Recruiting Sofia, Sofia-Grad, Bulgaria, 1632 Complex Oncology Center - Shumen EOOD Recruiting Shumen, Bulgaria, 9700 Italy Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST Recruiting Meldola, Italy, 47014 ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda Recruiting Milano, Italy, 20162 Poland Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Recruiting Krakow, Poland, 31826 Med-Polonia Sp. z o.o. Recruiting Poznan, Poland, 60693 Romania Fundeni Clinical Institute Recruiting Bucharest, Romania, 22328 Coltea Clinical Hospital Recruiting Bucharest, Romania, 30171 Prof Dr I Chiricuta Institute of Oncology Recruiting Cluj-Napoca, Romania, 400015 Oncology Center Sfantul Nectarie Recruiting Craiova, Romania, 200347 Euroclinic Oncology Center SRL Recruiting Iasi, Romania, 700106 Institutul Regional de Oncologie Iasi Recruiting Iasi, Romania, 700483 Collapse <<
  NCT00610740	-	-	Completed	-	-
  NCT00610740	Cervical Cancer ... more >> Endometrial Cancer Ovarian Cancer Collapse <<	Phase 2	Completed	-	United States, Minnesota ... more >> University of Minnesota Cancer Center Minneapolis, Minnesota, United States, 55455 Collapse <<

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• 参考文献

• [1] Hertel LW, Boder GB, et al. Evaluation of the antitumor activity of gemcitabine (2',2'-difluoro-2'-deoxycytidine). Cancer Res. 1990 Jul 15;50(14):4417-22.

  [2] Heinemann V, Xu YZ, et al. Cellular elimination of 2',2'-difluorodeoxycytidine 5'-triphosphate: a mechanism of self-potentiation. Cancer Res. 1992 Feb 1;52(3):533-9.

  [3] Huang P, Chubb S, et al. Action of 2',2'-difluorodeoxycytidine on DNA synthesis. Cancer Res. 1991 Nov 15;51(22):6110-7.

  [4] Shi Z, Azuma A, et al. S-Phase arrest by nucleoside analogues and abrogation of survival without cell cycle progression by 7-hydroxystaurosporine. Cancer Res. 2001 Feb 1;61(3):1065-72.

  [5] Action of 2',2'-Difluorodeoxycytidine on DNA Synthesis

  [6] Boven E, Schipper H, et al. The influence of the schedule and the dose of gemcitabine on the anti-tumour efficacy in experimental human cancer. Br J Cancer. 1993 Jul;68(1):52-6.

  [7] Chu W, Tian P, et al. Improving Plasma Stability and Bioavailability In Vivo of Gemcitabine Via Nanoparticles of mPEG-PLG-GEM Complexed with Calcium Phosphate. Pharm Res. 2018 Oct 11;35(12):230.

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