AP24534 帕纳替尼

目录号 M1648 所有产品仅供科研使用，严禁用于人或动物的治疗等任何其他用途，不为任何个人提供产品和服务

Ponatinib (AP24534)是一种新型有效的作用于Abl， PDGFRα， VEGFR2， FGFR1和Src的多靶点抑制剂， IC50分别为0.37 nM， 1.1 nM， 1.5 nM， 2.2 nM和5.4 nM。此外，Ponatinib hydrochloride也是RIPK1/3的双重抑制剂，能抑制细胞程序性坏死，并可用于急性淋巴细胞白血病和慢性髓细胞白血病的相关研究。

别名：Ponatinib

规格	价格	库存状态
Free Sample (0.5-1 mg)	¥ 0	中国库存现货
10mM*1mL in DMSO	¥ 720	中国库存现货
5mg	¥ 480	中国库存现货
10mg	¥ 660	中国库存现货
50mg	¥ 1740	中国库存现货
100mg	¥ 2640	中国库存现货

其他规格数量报价？

质量标准及产品资料

纯度： 99.79%
COA
MSDS
H-NMR
HPLC

产品信息

生物活性

Ponatinib (AP24534)是一种新型有效的作用于Abl， PDGFRα， VEGFR2， FGFR1和Src的多靶点抑制剂， IC50分别为0.37 nM， 1.1 nM， 1.5 nM， 2.2 nM和5.4 nM。Ponatinib是有效的可用于口服的多靶点激酶抑制剂，作用于野生型细胞,及T315I 突变细胞IC50分别为1.2和8.8nM。 Ponatinib抑制Ba/F3衍生细胞系的增殖。 Ponatinib作用于表达野生型或T315I突变型BCR-ABL的CML细胞系，有效抑制BCR-ABL调节的信号。

使用AbMole产品发表的文献

J Virol. 2020 Feb 14;94(5):e01791-19.

Targeting Kaposi's Sarcoma-Associated Herpesvirus ORF21 Tyrosine Kinase and Viral Lytic Reactivation by Tyrosine Kinase Inhibitors Approved for Clinical Use
Transl Stroke Res. 2017 Nov 4.

Combination of Emricasan with Ponatinib Synergistically Reduces Ischemia/Reperfusion Injury in Rat Brain Through Simultaneous Prevention of Apoptosis and Necroptosis

产品使用成果展示

	数据来源	Transl Stroke Res. (2017). Figure 7. Ponatinib (Abmole Bioscience, China)
	方法	i.g.
	细胞系/动物模型	rat
	浓度	20 mg/kg
	处理时间	24 h
	实验结果	Compared with sham group, the protein expressions of RIPK1, RIPK3, andMLKL in the rat brains were up-regulated in the I/R group, which were suppressed by ponatinib alone or combination with emricasan, whereas emricasan alone had no effect on the expressions of RIPK1, RIPK3, and MLKL (Fig. 7).

	数据来源	Transl Stroke Res. (2017). Figure 6. Ponatinib (Abmole Bioscience, China)
	方法	i.g.
	细胞系/动物模型	rat
	浓度	20 mg/kg
	处理时间	24 h
	实验结果	Compared with the sham group, there were significant increases in the caspase-3 and caspase-8 activities in the I/R-treated rat brains; these increases were obviously blocked in the presence of emricasan alone or together with ponatinib, whereas ponatinib alone did not affect the caspase-3 and caspase-8 activities (Fig. 6).

	数据来源	Transl Stroke Res. (2017). Figure 5. Ponatinib (Abmole Bioscience, China)
	方法	i.g.
	细胞系/动物模型	rat
	浓度	20 mg/kg
	处理时间	24 h
	实验结果	As displayed in Fig. 5, consistent with the results before, emricasan or ponatinib alone could reduce the neurological deficit score and infarct volume in the I/R-treated rats; these effects were obviously enhanced upon the combined application of emricasan and ponatinib.

	数据来源	Transl Stroke Res. (2017). Figure 4. Ponatinib (Abmole Bioscience, China)
	方法	i.g.
	细胞系/动物模型	rat
	浓度	20 mg/kg
	处理时间	24 h
	实验结果	As shown in Fig. 4, the neurological deficit score and infarct volume were obviously decreased in the presence of emricasan (A and B) or ponatinib (C and D) compared to that in the I/R group, whereas the vehicle of emricasan or ponatinib has no such effects.

	数据来源	Transl Stroke Res. (2017). Figure 3. Ponatinib (Abmole Bioscience, China)
	方法	i.g.
	细胞系/动物模型	rat
	浓度	20 mg/kg
	处理时间	24 h
	实验结果	Cerebral I/R caused dramatic increases in neurological deficit score and infarct volume; these increases were attenuated by pretreatment with emricasan (A and B) or ponatinib (C and D), whereas the vehicle of emricasan or ponatinib did not show such effects.

实验参考

体外实验*
细胞系	MV4-11, Kasumi-1, KG1, and EOL1 cells
方法	Cell viability assays. Cell viability was assessed using the Cell Titer 96 Aqueous One Solution Cell Proliferation Assay. Exponentially growing cell lines were plated into 96-well plates and incubated overnight at 37°C. Twenty-four hours after plating, cells were treated with compound or vehicle (dimethyl sulfoxide) for 72 hours. Absorbance was measured using a Wallac Victor microplate reader (PerkinElmer). Data are plotted as percent viability relative to vehicle-treated cells and the IC50 values (the concentration that causes 50% inhibition) are calculated using XLfit version 4.2.2 for Microsoft Excel. Data are shown as mean (±SD) from 3 separate experiments, each tested in triplicate.
浓度	0~100 nM
处理时间	72 h

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

体内实验*
动物模型	MV4-11 human tumor subcutaneous xenograft model
配制	aqueous 25 mmol/L citrate buffer (pH = 2.75)
剂量	1, 2.5, 5, 10, and 25 mg/kg/d once daily for 4 weeks
给药处理	orally

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

化学性质

分子量	532.56
分子式	C29H27F3N6O
CAS号	943319-70-8
溶解性（25°C）	DMSO ≥ 40 mg/mL
储存条件	粉末型式 -20°C 3年；4°C 2年溶于溶剂 -80°C 6个月；-20°C 1个月
运输方式	冰袋运输，根据产品的不同，可能会有相应调整。

储备液配制

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.8777 mL	9.3886 mL	18.7772 mL
5 mM	0.3755 mL	1.8777 mL	3.7554 mL
10 mM	0.1878 mL	0.9389 mL	1.8777 mL

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m²)	0.007	0.025	0.15	0.05	0.02	0.5
K_m 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的K_m系数
	动物 A的K_m系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

参考文献

[1] Chase et al. Haematologica. Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome.

[2] Ren et al. Leukemia. Ponatinib suppresses the development of myeloid and lymphoid malignancies associated with FGFR1 abnormalities.

[3] Sen et al. Mol Cancer Ther. The novel BCR-ABL and FLT3 inhibitor ponatinib is a potent inhibitor of the multidrug resistance-associated ATP-binding cassette transporter ABCG2.

[4] Lierman et al. Leukemia. Ponatinib is active against imatinib-resistant mutants of FIP1L1-PDGFRA and KIT, and against FGFR1-derived fusion kinases.

[5] Gozgit JM, et al. Mol Cancer Ther. Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies.

获取最新目录册

其他相关的Src-bcr-Abl产品
Asciminib hydrochloride Asciminib (ABL001) hydrochloride 是一种有效和选择性的变构 BCR-ABL1 抑制剂，抑制 Ba/F3 细胞生长的 IC50 值为 0.25 nM。
Osteogenic Growth Peptide (10-14) Osteogenic Growth Peptide (10-14) (OGP(10-14)), 是成骨生长肽 (OGP) C 端截短的五肽，保留了完整的 OGP 样活性。
Abl Cytosolic Substrate Abl Cytosolic Substrate是Abl 酪氨酸激酶的底物。
Ac-Tyr(PO3H2)-Glu-Glu-Ile-Glu-OH Ac-Tyr(PO3H2)-Glu-Glu-Ile-Glu-OH 是一种高亲和力的五肽，与 src SH2 域结合 (IC50≈1 µM)。
p60c-src substrate II p60c-src substrate II 是酪氨酸激酶 pp60c-src 的高效五肽底物。

信号通路

产品类型