Amuvatinib hydrochloride(Synonyms: MP470 hydrochloride; HPK 56 hydrochloride)

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

Amuvatinib hydrochloride (Synonyms: MP470 hydrochloride; HPK 56 hydrochloride)

Amuvatinib hydrochloride (MP470 hydrochloride) 是一种多靶点酪氨酸激酶抑制剂,对突变 c-KitPDGFRαFlt3c-Metc-Ret 具有有效活性。Amuvatinib hydrochloride (MP470 hydrochloride) 还是一种 DNA 修复抑制剂,靶向蛋白 DNA 修复 RAD51,从而破坏 DNA 损伤修复。具有抗肿瘤活性。

Amuvatinib hydrochloride(Synonyms: MP470 hydrochloride;  HPK 56 hydrochloride)

Amuvatinib hydrochloride Chemical Structure

CAS No. : 1055986-67-8

规格 是否有货
100 mg   询价  
250 mg   询价  
500 mg   询价  

* Please select Quantity before adding items.

Amuvatinib hydrochloride 的其他形式现货产品:

Amuvatinib

生物活性

Amuvatinib hydrochloride (MP470 hydrochloride) is an orally bioavailable multi-targeted tyrosine kinase inhibitor with potent activity against mutant c-Kit, PDGFRα, Flt3, c-Met and c-Ret. Amuvatinib hydrochloride (MP470 hydrochloride) is also a DNA repair suppressor through suppression of DNA repair protein RAD51, thereby disrupting DNA damage repair[1][2][3]. Antineoplastic activity[4].

IC50 & Target[1]

PDGFRαV561D

40 nM (IC50)

PDGFRαD842V

81 nM (IC50)

c-KitD816H

10 nM (IC50)

c-KitV560G

34 nM (IC50)

c-KitV654A

127 nM (IC50)

c-KitD816V

950 nM (IC50)

体外研究
(In Vitro)

Amuvatinib (MP470) inhibits c-Kit (D816V), c-Kit (D816H), c-Kit (V560G), c-Kit (V654A), PDGFRα (D842V), and PDGFRα (V561D) with IC50s of 950 nM, 10 nM, 34 nM, 127 nM, 81 nM, and 40 nM, respectively[4].
Amuvatinib (MP470), a novel receptor tyrosine kinase (RTK) inhibitor has shown growth inhibitory activity against a variety of cancer cell lines. Amuvatinib (0.1-10 μM, 4 days incubation) is effective on LNCaP and PC-3 cells with IC50s of ~4 μM and 8 μM, respectively. When Erlotinib (10 μM) is combined with varying doses of Amuvatinib, the IC50 of Amuvatinib decreases to 2 μM on LNCaP cells[5].
Akt activity (as measured by phosphorylation on Ser473) is significantly reduced by 10 μM Amuvatinib (treated for 30 hours) alone but is not reduced by Erlotinib or Imatinib Mesylate (IM). Moreover, Amuvatinib plus Erlotinib completely abolished Akt phosphorylation in LNCaP cells with an unchanged total protein level of Akt[5].

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.

Cell Viability Assay[2]

Cell Line: Prostate cancer cell lines (LNCaP, PC-3 and DU-145)
Concentration: 0.1-10 μM
Incubation Time: 4 days
Result: The IC50 for LNCaP and PC-3 was ~4 μM and 8 μM, respectively. Had only a modest effect on the viability of DU-145 cells.

Western Blot Analysis[2]

Cell Line: LNCaP cells
Concentration: 2,5,10 μM
Incubation Time: 30 hours
Result: Akt activity (as measured by phosphorylation on Ser473) was significantly reduced at 10 μM.

体内研究
(In Vivo)

Four LNCaP xenograft arms each with 12 mice are dosed intraperitoneally with DMSO (control) or Erlotinib 80 mg/kg or Amuvatinib (MP470) 50 mg/kg or Erlotinib 80 mg/kg plus Amuvatinib 50 mg/kg daily for 2 weeks and then observed for a further 11 days. Individual therapy with Amuvatinib or Erlotinib shows modest tumor growth inhibition (TGI), while Amuvatinib plus Erlotinib has a marked effect on TGI (45-65%). However, due to the high doses of Amuvatinib used, only five or one mouse remained alive in the combination arm at the end of treatment or at the end of the study, respectively. Therefore the Amuvatinib dose is reduced to 10 mg/kg or 20 mg/kg for the combination treatment. TGI in the group receiving 10 mg/kg Amuvatinib+80 mg/kg Erlotinib is not significantly different from the control group. However, mice receiving 20 mg/kg Amuvatinib+80 mg/kg Erlotinib have a significant TGI compared to the control group (p=0.01)[5].

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 Model: Forty eight 6-7 week-old SCID male mice with LNCaP xenograft model[2]
Dosage: 10 mg/kg and 20 mg/kg, 50 mg/kg
Administration: Administered i.p. daily from days 1 to 24
Result: Individual therapy showed modest tumor growth inhibition (TGI), while combination had a marked effect on TGI (45-65%).

Clinical Trial

Formula

C23H21N5O3S.xHCl

CAS 号

1055986-67-8

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]. Choy G, et al. Safety, tolerability, and pharmacokinetics of amuvatinib from three phase 1 clinical studies in healthy volunteers. Cancer Chemother Pharmacol. 2012 Jul;70(1):183-90.

    [2]. Baxter PA, et al. Plasma and cerebrospinal fluid pharmacokinetics of MP470 in non-human primates. Cancer Chemother Pharmacol. 2011 Apr;67(4):809-12.

    [3]. Tibes R, et al. A phase I, first-in-human dose-escalation study of amuvatinib, a multi-targeted tyrosine kinase inhibitor, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Feb;71(2):463-71.

    [4]. David J. Bearss, et al. Pharmaceutical formulations comprising salts of a protein kinase inhibitor and methods of using same. US20080226747A1.

    [5]. Qi W, et al. MP470, a novel receptor tyrosine kinase inhibitor, in combination with Erlotinib inhibits the HER family/PI3K/Akt pathway and tumor growth in prostate cancer. BMC Cancer. 2009 May 11;9:142.

所有产品仅用作科学研究或药证申报,我们不为任何个人用途提供产品和服务

Amuvatinib(Synonyms: MP470; HPK 56)

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

Amuvatinib (Synonyms: MP470; HPK 56) 纯度: 98.07%

Amuvatinib (MP470) 是一种多靶点酪氨酸激酶抑制剂,对突变 c-KitPDGFRαFlt3c-Metc-Ret 具有有效活性。Amuvatinib (MP470) 还是一种 DNA 修复抑制剂,靶向蛋白 DNA 修复 RAD51,从而破坏 DNA 损伤修复。具有抗肿瘤活性。

Amuvatinib(Synonyms: MP470;  HPK 56)

Amuvatinib Chemical Structure

CAS No. : 850879-09-3

规格 价格 是否有货 数量
Free Sample (0.1-0.5 mg)   Apply now  
10 mM * 1 mL in DMSO ¥1083 In-stock
2 mg ¥750 In-stock
5 mg ¥1100 In-stock
10 mg ¥1800 In-stock
50 mg ¥5400 In-stock
100 mg ¥9500 In-stock
200 mg   询价  
500 mg   询价  

* Please select Quantity before adding items.

Amuvatinib 相关产品

相关化合物库:

  • Drug Repurposing Compound Library Plus
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生物活性

Amuvatinib (MP470) is an orally bioavailable multi-targeted tyrosine kinase inhibitor with potent activity against mutant c-Kit, PDGFRα, Flt3, c-Met and c-Ret. Amuvatinib (MP470) is also a DNA repair suppressor through suppression of DNA repair protein RAD51, thereby disrupting DNA damage repair[1][2][3]. Antineoplastic activity[4].

IC50 & Target

PDGFRαV561D

40 nM (IC50)

PDGFRαD842V

81 nM (IC50)

c-KitD816H

10 nM (IC50)

c-KitV560G

34 nM (IC50)

c-KitV654A

127 nM (IC50)

c-KitD816V

950 nM (IC50)

体外研究
(In Vitro)

Amuvatinib (MP470) inhibits c-Kit (D816V), c-Kit (D816H), c-Kit (V560G), c-Kit (V654A), PDGFRα (D842V), and PDGFRα (V561D) with IC50s of 950 nM, 10 nM, 34 nM, 127 nM, 81 nM, and 40 nM, respectively[4].
Amuvatinib (MP470), a novel receptor tyrosine kinase (RTK) inhibitor has shown growth inhibitory activity against a variety of cancer cell lines. Amuvatinib (0.1-10 μM, 4 days incubation) is effective on LNCaP and PC-3 cells with IC50s of ~4 μM and 8 μM, respectively. When Erlotinib (10 μM) is combined with varying doses of Amuvatinib, the IC50 of Amuvatinib decreases to 2 μM on LNCaP cells[5].
Akt activity (as measured by phosphorylation on Ser473) is significantly reduced by 10 μM Amuvatinib (treated for 30 hours) alone but is not reduced by Erlotinib or Imatinib Mesylate (IM). Moreover, Amuvatinib plus Erlotinib completely abolished Akt phosphorylation in LNCaP cells with an unchanged total protein level of Akt[5].

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.

Cell Viability Assay[2]

Cell Line: Prostate cancer cell lines (LNCaP, PC-3 and DU-145)
Concentration: 0.1-10 μM
Incubation Time: 4 days
Result: The IC50 for LNCaP and PC-3 was ~4 μM and 8 μM, respectively. Had only a modest effect on the viability of DU-145 cells.

Western Blot Analysis[2]

Cell Line: LNCaP cells
Concentration: 2,5,10 μM
Incubation Time: 30 hours
Result: Akt activity (as measured by phosphorylation on Ser473) was significantly reduced at 10 μM.

体内研究
(In Vivo)

Four LNCaP xenograft arms each with 12 mice are dosed intraperitoneally with DMSO (control) or Erlotinib 80 mg/kg or Amuvatinib (MP470) 50 mg/kg or Erlotinib 80 mg/kg plus Amuvatinib 50 mg/kg daily for 2 weeks and then observed for a further 11 days. Individual therapy with Amuvatinib or Erlotinib shows modest tumor growth inhibition (TGI), while Amuvatinib plus Erlotinib has a marked effect on TGI (45-65%). However, due to the high doses of Amuvatinib used, only five or one mouse remained alive in the combination arm at the end of treatment or at the end of the study, respectively. Therefore the Amuvatinib dose is reduced to 10 mg/kg or 20 mg/kg for the combination treatment. TGI in the group receiving 10 mg/kg Amuvatinib+80 mg/kg Erlotinib is not significantly different from the control group. However, mice receiving 20 mg/kg Amuvatinib+80 mg/kg Erlotinib have a significant TGI compared to the control group (p=0.01)[5].

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 Model: Forty eight 6-7 week-old SCID male mice with LNCaP xenograft model[2]
Dosage: 10 mg/kg and 20 mg/kg, 50 mg/kg
Administration: Administered i.p. daily from days 1 to 24
Result: Individual therapy showed modest tumor growth inhibition (TGI), while combination had a marked effect on TGI (45-65%).

Clinical Trial

分子量

447.51

Formula

C23H21N5O3S

CAS 号

850879-09-3

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 : 50 mg/mL (111.73 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.2346 mL 11.1729 mL 22.3459 mL
5 mM 0.4469 mL 2.2346 mL 4.4692 mL
10 mM 0.2235 mL 1.1173 mL 2.2346 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°C, 6 months; -20°C, 1 month。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 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: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (5.59 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.59 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH₂O 中,得到澄清透明的生理盐水溶液

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [1]. Choy G, et al. Safety, tolerability, and pharmacokinetics of amuvatinib from three phase 1 clinical studies in healthy volunteers. Cancer Chemother Pharmacol. 2012 Jul;70(1):183-90.

    [2]. Tibes R, et al. A phase I, first-in-human dose-escalation study of amuvatinib, a multi-targeted tyrosine kinase inhibitor, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Feb;71(2):463-71.

    [3]. Baxter PA, et al. Plasma and cerebrospinal fluid pharmacokinetics of MP470 in non-human primates. Cancer Chemother Pharmacol. 2011 Apr;67(4):809-12.

    [4]. David J. Bearss, et al. Pharmaceutical formulations comprising salts of a protein kinase inhibitor and methods of using same. US20080226747A1.

    [5]. Qi W, et al. MP470, a novel receptor tyrosine kinase inhibitor, in combination with Erlotinib inhibits the HER family/PI3K/Akt pathway and tumor growth in prostate cancer. BMC Cancer. 2009 May 11;9:142.

所有产品仅用作科学研究或药证申报,我们不为任何个人用途提供产品和服务