Imatinib (STI571) 是一种口服生物可用的酪氨

Imatinib  (Synonyms: 伊马替尼; STI571; CGP-57148B)

Imatinib (STI571) 是一种口服生物可用的酪氨酸激酶抑制剂，可选择性抑制 BCR/ABL，v-Abl，PDGFR，c-kit 激酶活性。Imatinib (STI571) 靠近 ATP 结合位点结合，将其锁定在封闭或自我抑制的构象中，因此半竞争性抑制蛋白质的酶活性。Imatinib 还抑制 SARS-CoV 和 MERS-CoV。

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
MCE中国是全球领先的科研化学品和生物活性化合物供应商，总部位于美国新泽西。我们的产品范围覆盖各种抑制剂、激动剂、API和化合物库。专业、高效的企业灵魂铸造了在行业的卓越地位。热情和充满活力的研发团队拥有着大量的化学和生物科学家。专注于生物活性化合物，拥有着多年的发展历程和丰富的行业经验。

生物活性    
Imatinib (STI571) is an orally bioavailable tyrosine kinases inhibitor that selectively inhibits BCR/ABL, v-Abl, PDGFR and c-kit kinase activity. Imatinib (STI571) works by binding close to the ATP binding site, locking it in a closed or self-inhibited conformation, therefore inhibiting the enzyme activity of the protein semicompetitively[1][2][3][4]. Imatinib also is an inhibitor of SARS-CoV and MERS-CoV[5].

IC50 & Target    
BCR/ABL, v-Abl, PDGFR, c-kit[1][2][4]

体外研究(In Vitro)    
Imatinib (STI571) inhibits c-Kit autophosphorylation, activation of MAPK, and activation of Akt without altering total protein levels of c-kit, MAPK, or Akt. The concentration that produces 50% inhibition for these effects is approximately 100 nM[1].
Imatinib (STI571) is very effective (in vitro IC50 of 25 nM) against the chronic myeloid leukemia-causing kinase Bcr-Abl. Imatinib also efficiently inhibits Kit (in vitro IC50, 410 nM) and PDGFR (in vitro IC50, 380 nM)[2].
Imatinib (STI571) is a multi-target inhibitor of v-Abl, c-Kit and inhibits Bcr/Abl, v-Abl, Tel/Abl, the native PDGFβ receptor, and c-Kit, but it does not inhibit Src family kinases, c-Fms, Flt3, the EGFR or multiple other tyrosine kinases. Imatinib inhibits tyrosine phosphorylation and cell growth of Ba/F3 cells expressing Bcr/Abl, Tel/Abl, Tel/PDGFβR, and Tel/Arg with an IC50 of approximately 0.5 μM in each case, but it has no effect on untransformed Ba/F3 cells growing in IL-3 or on Ba/F3 cells transformed by Tel/JAK2[4].
The IC50s of Imatinib(STI571) is a multi-target inhibitor of v-Abl, c-Kit and on BON-1 and H727 cells after exposure for 48 h are 32.4 and 32.8 μM, respectively[6].

体内研究(In Vivo)    
In the phosphorothioate antisense oligodeoxynucleotides (PS-ASODN) group, tumor growth is inhibited by 59.437%, which is markedly higher than in the Imatinib (STI571) is a multi-target inhibitor of v-Abl, c-Kit and group (11.071%) and liposome negative control group (2.759%). Telomerase activity is significantly lower (P<0.01) in the PS-ASODN group (0.689±0.158) compare with the Imatinib group (1.838±0.241), liposome negative control group (2.013±0.273), and saline group (2.004±0.163)[7].
Imatinib (25 mg/kg/day, p.o.) suppresses the growth of endometriotic tissue and reduces the number of ovarian follicles in a rat model. Imatinib effectively treats experimental endometriosis by its inhibitor effects on angiogenesis and cell proliferation[8].

分子量    
493.60

性状    
Solid

Formula    
C29H31N7O

CAS 号    
152459-95-5

中文名称    
伊马替尼

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
4°C    2 years
In solvent    -80°C    1 year
-20°C    6 months
溶解性数据    
In Vitro: 
DMSO : 12.5 mg/mL (25.32 mM; Need ultrasonic)

H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    2.0259 mL    10.1297 mL    20.2593 mL
5 mM    0.4052 mL    2.0259 mL    4.0519 mL
10 mM    0.2026 mL    1.0130 mL    2.0259 mL
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 1 years; -20℃, 6 months。-80℃ 储存时，请在 1 年内使用， -20℃ 储存时，请在 6 个月 内使用。

In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 0.5% CMC-Na/saline water

Solubility: 11 mg/mL (22.29 mM); Suspended solution; Need ultrasonic

2.
请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 1.25 mg/mL (2.53 mM); Clear solution

3.
请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

Solubility: ≥ 1.25 mg/mL (2.53 mM); Clear solution

4.
请依序添加每种溶剂： 10% DMSO    90% corn oil

Solubility: ≥ 1.25 mg/mL (2.53 mM); Clear solution
 

参考文献

[1]. Heinrich MC, et al. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood. 2000 Aug 1;96(3):925-32.  [Content Brief] [2]. Guida T, et al. Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res. 2007 Jun 1;13(11):3363-9.  [Content Brief] [3]. Iqbal N, et al. Imatinib: a breakthrough of targeted therapy in cancer. Chemother Res Pract. 2014;2014:357027.  [Content Brief] [4]. Okuda K, et al. ARG tyrosine kinase activity is inhibited by STI571.Blood. 2001 Apr 15;97(8):2440-8  [Content Brief] [5]. Jeanne M Sisk, et al. Coronavirus S Protein-Induced Fusion Is Blocked Prior to Hemifusion by Abl Kinase Inhibitors. J Gen Virol. 2018 May;99(5):619-630.  [Content Brief] [6]. Yao JC, et al. Clinical and in vitro studies of imatinib in advanced carcinoid tumors. Clin Cancer Res. 2007 Jan 1;13(1):234-40.  [Content Brief] [7]. Sun XC, et al. Depletion of telomerase RNA inhibits growth of gastrointestinal tumors transplanted in mice. World J Gastroenterol. 2013 Apr 21;19(15):2340-7.  [Content Brief] [8]. Yildiz C, et al. Effect of imatinib on growth of experimental endometriosis in rats. Eur J Obstet Gynecol Reprod Biol. 2016 Feb;197:159-63.  [Content Brief] [9]. Coleman CM, et al, Frieman MB. Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion. J Virol. 2016;90(19):8924‐8933. Published 2016 Sep 12.  [Content Brief]