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Ponatinib

Ponatinib

产品编号 T2372   CAS 943319-70-8
别名: 帕纳替尼, AP24534, 普纳替尼

Ponatinib (AP24534) 是一种有口服活性的多靶点激酶抑制剂,抑制Abl、PDGFRα、VEGFR2、FGFR1和Src 的IC50分别为 0.37 nM、1.1 nM、1.5 nM、2.2 nM 和 5.4 nM。

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Ponatinib Chemical Structure
Ponatinib, CAS 943319-70-8
规格 价格/CNY 货期 数量
10 mg ¥ 669 现货
50 mg ¥ 1,900 现货
100 mg ¥ 2,683 现货
200 mg ¥ 3,940 现货
1 mL * 10 mM (in DMSO) ¥ 616 现货
其他形式的 Ponatinib:
千万补贴 助力科研
BCA蛋白浓度测定试剂盒限时半价
Venetoclax限时半价
产品目录号及名称: Ponatinib (T2372)
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纯度: 99.65%
纯度: 99.58%
纯度: 99.57%
纯度: 98%
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生物活性
化学信息
存储 & 溶解度
参考文献
产品描述 Ponatinib (AP24534) is an orally available, multitargeted kinase inhibitor (IC50s: 0.37/1.1/1.5/2.2/5.4 nM for Abl, PDGFRα, VEGFR2, FGFR1, and Src, respectively).
靶点活性 PDGFRα:1.1 nM (cell free), c-Src:5.4 nM (cell free), Abl:0.37 nM (cell free), FGFR1:2.2 nM (cell free), Lyn:0.24 nM (cell free), VEGFR2:1.5 nM (cell free)
体外活性 Ponatinib (AP24534) potently inhibited native ABL (IC50: 0.37 nM), ABL T315I (IC50: 2.0 nM), and other clinically important ABL kinase domain mutants (IC50: 0.30–0.44 nM). AP24534 also inhibited SRC (IC50: 5.4 nM) and members of the VEGFR, FGFR, and PDGFR families of receptor tyrosine kinases. AP24534 did not inhibit Aurora kinase family members, nor did it inhibit the insulin receptor or CDK2/Cyclin E. AP24534 potently inhibited proliferation of Ba/F3 cells expressing native BCR-ABL (IC50: 0.5 nM). All BCR-ABL mutants tested remained sensitive to AP24534 (IC50: 0.5–36 nM) including BCR-ABLT315I (IC50: 11 nM) [1]. Treatment with ponatinib efficiently inhibited the growth of CMPs expressing Hes1 with F/P, F/P-T674I, or F/P-D842V with an IC50 of 0.15 nM, 0.35 nM, or 1.71 nM, respectively. In accordance, ponatinib dose-dependently suppressed the activation of F/P and its downstream STAT5 and ERK in these cytokine-independent cells [2]. Ponatinib potently inhibits receptor phosphorylation and cellular proliferation with IC50 values comparable to those required for inhibition of BCR-ABL (0.3 to 20 nmol/L) [3].
体内活性 Daily oral treatment with 2.5 or 5 mg/kg AP24534 for 19 days prolonged median survival to 27.5 and 30 days, respectively. In a xenograft model of Ba/F3 BCR-ABLT315I cells, tumor growth was inhibited by AP24534 in a dose-dependent manner compared to vehicle-treated mice, with significant suppression of tumor growth upon daily oral dosing at 10 and 30 mg/kg. Daily oral dosing of 50 mg/kg AP24534 caused significant tumor regression, with a 96% reduction in mean tumor volume at the final measurement compared to the start of treatment [1]. Ponatinib (1–25 mg/kg, p.o.) was administered orally, once daily for 28 days, to mice bearing MV4-11 xenografts. ponatinib potently inhibited tumor growth in a dose-dependent manner. Administration of 1 mg/kg led to significant inhibition of tumor growth (TGI = 46%) and doses of 2.5 mg/kg or greater resulted in tumor regression. Dosing with 10 or 25 mg/kg led to complete and durable tumor regression [3].
激酶实验 AP24534 was profiled against >100 kinases by Reaction Biology Corporation using the Kinase Hotspot assay, which utilizes 10 μM [33P]-ATP, recombinant kinase domain, peptide substrate, and a range of 10 concentrations of inhibitor to establish an IC50 value [1].
细胞实验 Ba/F3 cell lines were distributed in 96-well plates (4 × 10^3 cells/well) and incubated with escalating concentrations of AP24534 for 72 hr. The inhibitor ranges used were: 0–625 nM for cells expressing BCR-ABL and 0–10,000 nM for BCR-ABL negative cells. Proliferation was measured using an MTS-based viability assay. IC50 values are reported as the mean of three independent experiments performed in quadruplicate. For cell proliferation experiments with CML or normal primary cells, mononuclear cells were plated in 96-well plates (5 × 10^4 cells/well) over graded concentrations of AP24534 (0–1000 nM) in RPMI supplemented with 10% FBS, L-glutamine, penicillin/streptomycin, and 100 μM β-mercaptoethanol. Following a 72 hr incubation, cell viability was assessed by subjecting cells to an MTS assay. All values were normalized to the control wells with no drug [1].
动物实验 Briefly, tumor xenografts were established by the subcutaneous implantation of MV4-11 cells (1 × 10^7 in 50% Matrigel) into the right flank of female CB.17 severe combined immunodeficient mice and dosing was initiated when the average tumor volume reached approximately 200 mm^3. Ponatinib was formulated in aqueous 25 mmol/L citrate buffer (pH = 2.75) and mice were dosed orally once daily for 4 weeks. The tumors were measured in 2 dimensions (length and width) with a caliper in millimeters. Tumor volume (mm3) was calculated with the following formula: tumor volume = (length × width^2)/2. Tumor growth inhibition (TGI) was calculated as follows: TGI = (1 ? ΔT/ΔC) × 100, where ΔT stands for mean tumor volume change of each treatment group and ΔC for mean tumor volume change of control group. The tumor volume data were collected and analyzed with a 1-way ANOVA test to determine the overall difference among groups. Each ponatinib treatment group was further compared to the vehicle control group for statistical significance using Dunnett's Multiple Comparison Test. A P-value less than 0.05 was considered to be statistically significant and a P-value less than 0.01 to be highly statistically significant [3].
别名 帕纳替尼, AP24534, 普纳替尼
化合物与蛋白结合的复合物

T2372_2

FGFR1 in complex with ponatinib.

分子量 532.56
分子式 C29H27F3N6O
CAS No. 943319-70-8

存储

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度

Ethanol: 26.6 mg/mL (50 mM)

DMSO: 53.3 mg/mL (100 mM)

溶液配制表

可选溶剂 浓度 体积 质量 1 mg 5 mg 10 mg 25 mg
Ethanol / DMSO 1 mM 1.8777 mL 9.3886 mL 18.7772 mL 46.9431 mL
5 mM 0.3755 mL 1.8777 mL 3.7554 mL 9.3886 mL
10 mM 0.1878 mL 0.9389 mL 1.8777 mL 4.6943 mL
20 mM 0.0939 mL 0.4694 mL 0.9389 mL 2.3472 mL
50 mM 0.0376 mL 0.1878 mL 0.3755 mL 0.9389 mL
DMSO 100 mM 0.0188 mL 0.0939 mL 0.1878 mL 0.4694 mL

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TargetMol Library Books参考文献

1. O'Hare T, et al. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell, 2009, 16(5), 401-412. 2. Uchida T, et al. Hes1 upregulation contributes to the development of FIP1L1-PDGRA-positive leukemia in blast crisis. Exp Hematol. 2014 May;42(5):369-379.e3. 3. Gozgit JM, et al. Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies. Mol Cancer Ther, 2011, 10(6), 1028-1035. 4. Lin H, Lu P, Zhou M, et al. Purification of recombinant human fibroblast growth factor 13 in E. coli and its molecular mechanism of mitogenesis[J]. Applied microbiology and biotechnology. 2019: 1-11.

TargetMol Library Books文献引用

1. Cheng S, Jin P, Li H, et al. Evaluation of CML TKI Induced Cardiovascular Toxicity and Development of Potential Rescue Strategies in a Zebrafish Model. Frontiers in Pharmacology. 2021: 2866. 2. Lin H, Lu P, Zhou M, et al. Purification of recombinant human fibroblast growth factor 13 in E. coli and its molecular mechanism of mitogenesis. Applied Microbiology and Biotechnology. 2019: 1-11 3. Yan H, Wu W, Hu Y, et al.Regorafenib inhibits EphA2 phosphorylation and leads to liver damage via the ERK/MDM2/p53 axis.Nature Communications.2023, 14(1): 2756. 4. Oeller M, Jaksch-Bogensperger H, Templin M, et al.Transcription Factors STAT3 and MYC Are Key Players of Human Platelet Lysate-Induced Cell Proliferation.International Journal of Molecular Sciences.2022, 23(24): 15782.
AZD4547 Sprengerinin C Sorafenib-d3 VEGFR-2-IN-36 Parsatuzumab Toceranib VEGFR-2-IN-29 CP-547632 TFA

相关化合物库

该产品包含在如下化合物库中:
抑制剂库 FDA 上市激酶抑制剂库 抗癌药物库 抗癌临床化合物库 药物功能重定位化合物库 激酶抑制剂库 酪氨酸激酶分子库 膜蛋白靶向化合物库 抗癌活性化合物库 EMA 上市药物库

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Keywords

Ponatinib 943319-70-8 Angiogenesis Autophagy Cytoskeletal Signaling Tyrosine Kinase/Adaptors VEGFR FGFR Bcr-Abl PDGFR Src c-Kit 帕纳替尼 Platelet-derived growth factor receptor orally inhibit multi-targeted VEGFR2 Fibroblast growth factor receptor Abl active AP 24534 Inhibitor AP-24534 PDGFRα kinase FGFR1 AP24534 Vascular endothelial growth factor receptor 普纳替尼 inhibitor

 

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