Nilotinib-d3 (AMN107-d3) is the deuterium labeled Nilotinib. Nilotinib is an orally available Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity[1][2].
体外研究 (In Vitro)
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
532.53
Formula
C28H19D3F3N7O
CAS 号
1215678-43-5
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Weisberg E, et al. Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias. Blood. 2007 Mar 1;109(5):2112-20.
[3]. Sako H, et al. Antitumor effect of the tyrosine kinase inhibitor Nilotinib on gastrointestinal stromal tumor (GIST) and Imatinib-resistant GIST cells. PLoS One. 2014 Sep 15;9(9):e107613.
[4]. Dervis Hakim G, et al. Mucosal healing effect of nilotinib in indomethacin-induced enterocolitis: A rat model. World J Gastroenterol. 2015 Nov 28;21(44):12576-85.
[5]. Fujita KI, et al. Involvement of the Transporters P-Glycoprotein and Breast Cancer Resistance Protein in Dermal Distribution of the Multikinase Inhibitor Regorafenib and Its Active Metabolites. J Pharm Sci. 2017 Sep;106(9):2632-2641.
[6]. Meirson T, et al. Targeting invadopodia-mediated breast cancer metastasis by using ABL kinase inhibitors. Oncotarget. 2018 Apr 24;9(31):22158-22183.
Nilotinib D6 (AMN107 D6) is a deuterium labeled Nilotinib. Nilotinib is an orally available Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity[1].
分子量
535.55
Formula
C28H16D6F3N7O
CAS 号
1268356-17-7
中文名称
尼洛替尼 d6
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Weisberg E, et al. Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias. Blood. 2007 Mar 1;109(5):2112-20.
Nilotinib monohydrochloride monohydrate is a second generation tyrosine kinase inhibitor (TKI), is significantly potent against BCR-ABL, and is active against many BCR-ABL mutants.
IC50 & Target
Bcr-Abl[1]
体外研究 (In Vitro)
The novel, selective Abl inhibitor, Nilotinib (AMN107), is designed to interact with the ATP-binding site of BCR-ABL with a higher affinity than Imatinib. In addition to being significantly more potent compared with Imatinib (IC50<30 nm), nilotinib also maintains activity against most of the bcr-abl point mutants that confer imatinib resistance[1]. Nilotinib demonstrates significant antitumor efficacy against GIST xenograft lines and Imatinib-resistant GIST cell lines. The parent cell lines GK1C and GK3C show Imatinib sensitivity with IC50 of 4.59±0.97 µM and 11.15±1.48 µM, respectively. The Imatinib-resistant cell lines GK1C-IR and GK3C-IR show Imatinib resistance with IC50 values of 11.74±0.17 µM (P<0.001) and 41.37±1.07 µM (P<0.001), respectively[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
The percentage of tumor growth inhibition (TGI) is 83.8% for Imatinib and 69.6% for Nilotinib in the GK1X xenograft line (n.s.). In the GK2X xenograft line, TGI is 83.0% for Imatinib and 85.3% for Nilotinib (n.s.). Additionally, the GK3X xenograft line TGI is 31.1% for Imatinib and 47.5% for Nilotinib (n.s.). These results suggest that, except for the GK1X xenograft line, Nilotinib shows equivalent or higher antitumor effects than Imatinib[2]. Nilotinib has a significant healing effect on the macroscopic and microscopic pathologic scores and ensures considerable mucosal healing in the indomethacin-induced enterocolitis rat model. While Nilotinib decreased the PDGFR α and β levels and apoptotic scores in the colon, it did not have a significant effect on the weight and TNF-α levels. Further experimental investigations could provide more definitive evidence for humans[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
583.99
Formula
C28H25ClF3N7O2
CAS 号
923288-90-8
中文名称
尼洛替尼盐酸盐一水合物;尼罗替尼盐酸盐一水合物
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Weisberg E, et al. Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias. Blood. 2007 Mar 1;109(5):2112-20.
[2]. Sako H, et al. Antitumor effect of the tyrosine kinase inhibitor Nilotinib on gastrointestinal stromal tumor (GIST) and Imatinib-resistant GIST cells. PLoS One. 2014 Sep 15;9(9):e107613.
[3]. Dervis Hakim G, et al. Mucosal healing effect of nilotinib in indomethacin-induced enterocolitis: A rat model. World J Gastroenterol. 2015 Nov 28;21(44):12576-85.
Cell Assay [2]
The human GIST cell lines GK1C and GK3C, and the Imatinib-resistant cell lines GK1C-IR and GK3C-IR are plated in 96-well microplates and cultured for 12 h before exposure to Imatinib (1-100 µM) or Nilotinib (1-100 µM) for 72 h. The cells are quantified by the WST-8 assay. The optical density (OD) is determined with Sunrise rainbow. The rate of inhibition is calculated as follows: % of inhibition=(OD of treated group-blank)/(OD of control group-blank)×100%. The concentration of tested drugs resulting in 50% growth inhibition (IC50) is calculated[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [2][3]
Mice[2] The GIST xenograft lines GK1X, GK2X and GK3X in nude mice are used. These xenograft lines are maintained by continual passage in BALB/cSLc-nu/nu mice. Mice bearing GK1X, GK2X and GK3X tumors (6-8 mice per group) are treated daily with vehicle or 40 mg/kg Imatinib or Nilotinib for 4 weeks. Tumor volume (TV) is determined from caliper measurements of tumor length (L) and width (w) according to the formula LW2/2. TV is determined every two to three days and on the day of evaluation. Mice are sacrificed and the percentage of tumor growth inhibition (TGI) is calculated as follows: TGI (%)=[1-(mean of treatment group tumor volume on evaluation day-mean of treatment group tumor volume on day 1)/(mean of control group tumor volume on evaluation day-mean of control group tumor volume on day 1)]×100. Rats[3] Female Wistar albino rats, weighing 226-243 g (mean weight, 241.09 g), for use in this study. Nilotinib, administered 20 mg/kg/d in two divided doses, is administered to the Nilotinib group of rats (n=7) for 13 d through an orogastric tube, beginning on the same day as indomethacin administration. Blood and tissue samples for pathological examination are obtained from all rats under ether anesthesia at the end of the 13-d period. All animals are then sacrificed by decapitation.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Weisberg E, et al. Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias. Blood. 2007 Mar 1;109(5):2112-20.
[2]. Sako H, et al. Antitumor effect of the tyrosine kinase inhibitor Nilotinib on gastrointestinal stromal tumor (GIST) and Imatinib-resistant GIST cells. PLoS One. 2014 Sep 15;9(9):e107613.
[3]. Dervis Hakim G, et al. Mucosal healing effect of nilotinib in indomethacin-induced enterocolitis: A rat model. World J Gastroenterol. 2015 Nov 28;21(44):12576-85.
Nilotinib is an orally available Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity.
IC50 & Target
Bcr-Abl[1]
体外研究 (In Vitro)
The novel, selective Abl inhibitor, Nilotinib (AMN107), is designed to interact with the ATP-binding site of BCR-ABL with a higher affinity than Imatinib. In addition to being significantly more potent compared with Imatinib (IC50<30 nm), nilotinib also maintains activity against most of the bcr-abl point mutants that confer imatinib resistance[1]. Nilotinib demonstrates significant antitumor efficacy against GIST xenograft lines and Imatinib-resistant GIST cell lines. The parent cell lines GK1C and GK3C show Imatinib sensitivity with IC50 of 4.59±0.97 µM and 11.15±1.48 µM, respectively. The Imatinib-resistant cell lines GK1C-IR and GK3C-IR show Imatinib resistance with IC50 values of 11.74±0.17 µM (P<0.001) and 41.37±1.07 µM (P<0.001), respectively[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
The percentage of tumor growth inhibition (TGI) is 83.8% for Imatinib and 69.6% for Nilotinib in the GK1X xenograft line (n.s.). In the GK2X xenograft line, TGI is 83.0% for Imatinib and 85.3% for Nilotinib (n.s.). Additionally, the GK3X xenograft line TGI is 31.1% for Imatinib and 47.5% for Nilotinib (n.s.). These results suggest that, except for the GK1X xenograft line, Nilotinib shows equivalent or higher antitumor effects than Imatinib[2]. Nilotinib has a significant healing effect on the macroscopic and microscopic pathologic scores and ensures considerable mucosal healing in the indomethacin-induced enterocolitis rat model. While Nilotinib decreased the PDGFR α and β levels and apoptotic scores in the colon, it did not have a significant effect on the weight and TNF-α levels. Further experimental investigations could provide more definitive evidence for humans[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
529.52
Formula
C28H22F3N7O
CAS 号
641571-10-0
中文名称
尼洛替尼;尼罗替尼
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
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : < 1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble or slightly soluble)
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:
[1]. Weisberg E, et al. Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias. Blood. 2007 Mar 1;109(5):2112-20.
[2]. Sako H, et al. Antitumor effect of the tyrosine kinase inhibitor Nilotinib on gastrointestinal stromal tumor (GIST) and Imatinib-resistant GIST cells. PLoS One. 2014 Sep 15;9(9):e107613.
[3]. Dervis Hakim G, et al. Mucosal healing effect of nilotinib in indomethacin-induced enterocolitis: A rat model. World J Gastroenterol. 2015 Nov 28;21(44):12576-85.
[4]. Fujita KI, et al. Involvement of the Transporters P-Glycoprotein and Breast Cancer Resistance Protein in Dermal Distribution of the Multikinase Inhibitor Regorafenib and Its Active Metabolites. J Pharm Sci. 2017 Sep;106(9):2632-2641.
[5]. Meirson T, et al. Targeting invadopodia-mediated breast cancer metastasis by using ABL kinase inhibitors. Oncotarget. 2018 Apr 24;9(31):22158-22183.
Cell Assay [2]
The human GIST cell lines GK1C and GK3C, and the Imatinib-resistant cell lines GK1C-IR and GK3C-IR are plated in 96-well microplates and cultured for 12 h before exposure to Imatinib (1-100 µM) or Nilotinib (1-100 µM) for 72 h. The cells are quantified by the WST-8 assay. The optical density (OD) is determined with Sunrise rainbow. The rate of inhibition is calculated as follows: % of inhibition=(OD of treated group-blank)/(OD of control group-blank)×100%. The concentration of tested drugs resulting in 50% growth inhibition (IC50) is calculated[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [2][3]
Mice[2] The GIST xenograft lines GK1X, GK2X and GK3X in nude mice are used. These xenograft lines are maintained by continual passage in BALB/cSLc-nu/nu mice. Mice bearing GK1X, GK2X and GK3X tumors (6-8 mice per group) are treated daily with vehicle or 40 mg/kg Imatinib or Nilotinib for 4 weeks. Tumor volume (TV) is determined from caliper measurements of tumor length (L) and width (w) according to the formula LW2/2. TV is determined every two to three days and on the day of evaluation. Mice are sacrificed and the percentage of tumor growth inhibition (TGI) is calculated as follows: TGI (%)=[1-(mean of treatment group tumor volume on evaluation day-mean of treatment group tumor volume on day 1)/(mean of control group tumor volume on evaluation day-mean of control group tumor volume on day 1)]×100. Rats[3] Female Wistar albino rats, weighing 226-243 g (mean weight, 241.09 g), for use in this study. Nilotinib, administered 20 mg/kg/d in two divided doses, is administered to the Nilotinib group of rats (n=7) for 13 d through an orogastric tube, beginning on the same day as indomethacin administration. Blood and tissue samples for pathological examination are obtained from all rats under ether anesthesia at the end of the 13-d period. All animals are then sacrificed by decapitation.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Weisberg E, et al. Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias. Blood. 2007 Mar 1;109(5):2112-20.
[2]. Sako H, et al. Antitumor effect of the tyrosine kinase inhibitor Nilotinib on gastrointestinal stromal tumor (GIST) and Imatinib-resistant GIST cells. PLoS One. 2014 Sep 15;9(9):e107613.
[3]. Dervis Hakim G, et al. Mucosal healing effect of nilotinib in indomethacin-induced enterocolitis: A rat model. World J Gastroenterol. 2015 Nov 28;21(44):12576-85.
[4]. Fujita KI, et al. Involvement of the Transporters P-Glycoprotein and Breast Cancer Resistance Protein in Dermal Distribution of the Multikinase Inhibitor Regorafenib and Its Active Metabolites. J Pharm Sci. 2017 Sep;106(9):2632-2641.
[5]. Meirson T, et al. Targeting invadopodia-mediated breast cancer metastasis by using ABL kinase inhibitors. Oncotarget. 2018 Apr 24;9(31):22158-22183.