CAS |
95058-81-4 |
Chinese Name |
吉西他滨 |
English Name |
Gemcitabine |
Synonyms |
LY188011;NSC 613327 |
Molecular Formula |
C9H11F2N3O4 |
Molecular Weight |
263.2 |
Solubility |
Soluble in Water/DMSO ≥3mg/mL |
Purity |
HPLC≥98% |
Appearance |
White to off-white Solid |
Storage |
Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year |
EC |
EINECS 619-100-6 |
MDL |
MFCD00869720 |
SMILES |
O=C1N(C=CC(N)=N1)[C@H]2C(F)([C@@H]([C@H](O2)CO)O)F |
InChIKey |
SDUQYLNIPVEERB-QPPQHZFASA-N |
InChI |
InChI=1S/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m1/s1 |
PubChem CID |
60750 |
Target Point |
DNA/RNA Synthesis |
Passage |
Cell Cycle;DNA Damage/DNA Repair |
Background |
Gemcitabine is a DNA synthesis inhibitor. Is a pyrimidine nucleoside analog. It can inhibit DNA synthesis and repair, leading to autophagy and apoptosis. |
Biological Activity |
Gemcitabine (NSC 613327;LY188011) 是一种 DNA合成 抑制剂,抑制 BxPC-3,Mia Paca-2,PANC-1,PL-45 和 AsPC-1细胞生长的 IC50 分别为 37.6, 42.9, 92.7, 89.3 和 131.4 nM[1-5]。 |
In Vitro |
MTS测定证明,15nM的吉西他滨,50μM的吲哚-3-甲醇(I3C)和该组合不影响hTERT-HPNE细胞活力。然而,用15nM的吉西他滨,50μM的I3C和该组合治疗分别导致BxPC-3细胞31%,19%和72%的细胞死亡[1]。 |
In Vivo |
治疗LSL-KrasG12D/+; LSL-Trp53R172H;与安慰剂组相比,使用吉西他滨(50 mg/kg,ip)或组合DMAPT /吉西他滨的Pdx-1-Cre小鼠显著增加中位生存时间超过30天(254.5 [P = 0.015]或255天[ P = 0.018]分别为217.5天)[2]。吉西他滨可通过大鼠气管内喷雾给药,无明显毒性,最大耐受剂量为4mg/kg,每周一次,持续9周。在剂量为2,4和6 mg/kg时,吉西他滨的毒性低于口服给药[3]。 |
Cell Experiment |
将细胞(人胰腺细胞系,Mia PaCa-2,BxPC-3,AsPC-1,PANC-1,PL-45和正常胰腺导管上皮细胞,hTERT-HPNE细胞)接种到96孔板中(3000细胞/孔)一式三份。孵育过夜后,更换培养基并用I3C和/或NBMPR处理细胞24小时。再次更换培养基,并在存在或不存在相同浓度的I3C和/或NBMPR的情况下,在含有不同浓度的吉西他滨的培养基中培养细胞48小时。然后按照制造商的说明对细胞进行CellTiter 96 AQueous One Solution Cell Proliferation Assay(MTS)。在加入20μLMTS试剂/孔后2小时测量490nm处的吸光度[1]。 |
Animal Experiment |
小鼠[2]在1个月大时,LSL-KrasG12D/+; LSL-Trp53R172H;将Pdx-1-Cre小鼠随机分入治疗组(安慰剂,DMAPT,吉西他滨,DMAPT /吉西他滨)。安慰剂(载体=羟丙基甲基纤维素,0.2%吐温80 [HPMT])和DMAPT(HPMT中40mg/kg体重)通过每天一次口服洗胃施用。每周两次通过腹膜内注射施用吉西他滨(PBS中50mg/kg体重)。每周监测小鼠体重。继续治疗直至小鼠出现嗜睡,腹胀或体重减轻的迹象,此时将其处死。通过检测单个LoxP位点的存在,在小鼠胰腺中确认成功的切除 - 重组事件。大鼠[3]该研究在80只雌性Wistar大鼠中进行,初始重量约为250g。通过耳标识别动物并如下分组。将40只大鼠分成5组,每组8只:4组通过气管内喷雾分别以2,4,6和8mg/kg的剂量肺组织给予吉西他滨(LD2,LD4,LD6,LD8组)和一组接受0.9%盐水载体溶液(组LDv)的喷雾给药。将剩余的40只大鼠分成5组,每组8只:4组分别通过管饲法分别以2,4,6和8mg/kg的剂量口服递送吉西他滨(OD2,OD4,OD6,OD8组),组通过管饲法接受相同体积的0.9%盐水(组ODv)。该协议包括以1周为间隔的九个会话。在两个疗程之间,将动物保持在标准实验室条件下,并在每个笼子中由四只动物的一组饲养,其中有垫料并且可以自由获得颗粒食物和自来水。将笼子放置在与抽吸系统连接的封闭腔室中。 |
Data Literature Source |
[1]. Wang H,et al. Enhanced efficacy of Gemcitabine by indole-3-carbinol in pancreatic cell lines: the role of human equilibrativenucleoside transporter 1. Anticancer Res. 2011 Oct;31(10):3171-80. [2]. Yip-Schneider MT,et al. Dimethylaminoparthenolide and Gemcitabine: a survival study using a genetically engineered mouse model of pancreatic cancer. BMC Cancer. 2013 Apr 17;13:194. [3]. Gagnadoux F,et al. Safety of pulmonary administration of gemcitabine in rats. J Aerosol Med. 2005 Summer;18(2):198-206 [4]. Lou M,et al. Physical interaction between human ribonucleotide reductase large subunit and thioredoxin increases colorectal cancer malignancy. J Biol Chem. 2017 Jun 2;292(22):9136-9149. [5]. Wang Y,et al. Licoricidin enhances gemcitabine-induced cytotoxicity in osteosarcoma cells by suppressing the Akt and NF-κB signal pathways. Chem Biol Interact. 2018 May 18;290:44-51. |
Unit |
Bottle |
Specification |
10mg 10mM*1mL in DMSO 50mg |