Ponatinib (AP24534)

Catalog No.S1490

For research use only.

Ponatinib (AP24534) is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM in cell-free assays, respectively. Ponatinib (AP24534) inhibits autophagy.

Ponatinib (AP24534) Chemical Structure

CAS No. 943319-70-8

Selleck's Ponatinib (AP24534) has been cited by 166 publications

Purity & Quality Control

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Biological Activity

Description Ponatinib (AP24534) is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM in cell-free assays, respectively. Ponatinib (AP24534) inhibits autophagy.
Targets
Abl [1]
(Cell-free assay)
PDGFRα [1]
(Cell-free assay)
VEGFR2 [1]
(Cell-free assay)
FGFR1 [1]
(Cell-free assay)
c-Src [1]
(Cell-free assay)
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0.37 nM 1.1 nM 1.5 nM 2.2 nM 5.4 nM
In vitro

AP24534 potently inhibits native Abl, AblT315I, and other clinically important Abl kinase domain mutants with IC50 of 0.30 nM–2 nM. AP24534 doesn't inhibit Aurora kinase family members, nor does it inhibit insulin receptor or CDK2/cyclin E. AP24534 inhibits proliferation of Ba/F3 cells expressing Bcr-Abl with IC50 of 0.5 nM, as well as Ba/F3 cells expressing a range of Bcr-Abl mutants with IC50 of 0.5 nM–36 nM. The inhibition of proliferation by AP24534 is correlated with induction of apoptosis. [1-2] In leukemic cell lines containing activated forms of FLT3, KIT, FGFR1, and PDGFRα receptors, AP24534 potently inhibits receptor phosphorylation and cellular proliferation with IC50 of 0.3 nM to 20 nM. In MV4-11 (FLT3-ITD(+/+)) but not RS4;11 (FLT3-ITD(–/–)) AML cells, AP24534 inhibits FLT3 signaling and induced apoptosis at less than 10 nM. AP24534 inhibits viability of primary leukemic blasts from a FLT3-ITD positive AML patient with IC50 of 4 nM but not those from patients with AML expressing native FLT3. [3] In Ba/F3 cells engineered to express activated FGFR1-4, AP24534 potently inhibits FGFR-mediated signaling and viability with IC50 lower than 40 nM. In cell lines representing multiple tumor types (endometrial, bladder, gastric, breast, lung, and colon), and containing FGFRs dysregulated by a variety of mechanisms, AP24534 inhibits FGFR-mediated signaling with IC50 less than 40 nM and inhibits cell growth with IC50 of 7 nM–181 nM. [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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MV-4-11 NI\lUJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXrJR|UxRTBwMECwNFk2PiEQvF2= NULtbJd2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
MEG-01 M1zP[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3m1PGlEPTB;MD6wNFAyOjhizszN MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
LAMA-84 MoLkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX\JR|UxRTBwMECwNVY2KM7:TR?= MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
CGTH-W-1 NECyVplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4nFVmlEPTB;MD6wNFE3QSEQvF2= M2n6dlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzF6M{evK|5USU6JRWK8M4E,
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BE-13 NIK1d49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGL4SGhKSzVyPUCuNFAzPTlizszN MoXYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OTh|Nz:nQnNCVkeHUkyvZV4>
CTV-1 NIDNcHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4DycWlEPTB;MD6wNFUzOSEQvF2= MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
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KYSE-70 NF31[|dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVzQZnY3UUN3ME2zMlA5QDh{IN88US=> M1jVTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzF6M{evK|5USU6JRWK8M4E,
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LB2518-MEL M1XRXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUHJR|UxRTR2Lke5N|ch|ryP NUfCcVluRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
TE-5 NXrMfJZXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYjHPXJFUUN3ME20OU46PThzIN88US=> MlHMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OTh|Nz:nQnNCVkeHUkyvZV4>
EW-24 NFfYRlZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnvxTWM2OD12Nj6xO|I{KM7:TR?= NWPNXlFxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
LB647-SCLC NYLvZWhqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M36xXmlEPTB;NE[uNlE2PSEQvF2= NGnQS4U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTdzOEO3M{c,W0GQR1XSQE9iRg>?
NCI-H524 M{\lfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEXPOoVKSzVyPUS2MlcyQDVizszN Mn\VQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OTh|Nz:nQnNCVkeHUkyvZV4>
EW-11 M3XMeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXT2NVZzUUN3ME20Ok46Ozd|IN88US=> MmjuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OTh|Nz:nQnNCVkeHUkyvZV4>
KALS-1 NV\2WGs3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2f4Z2lEPTB;NEeuNlA3PiEQvF2= NF\P[FU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTdzOEO3M{c,W0GQR1XSQE9iRg>?
BT-474 M13Uemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUXLUZNyUUN3ME20O{41OjF4IN88US=> MmG3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OTh|Nz:nQnNCVkeHUkyvZV4>
SK-N-AS NH\3fFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHvqdnJKSzVyPUS3Mlg5QCEQvF2= MnTpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OTh|Nz:nQnNCVkeHUkyvZV4>
HCC2157 M3nnZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFuxUZBKSzVyPUS4MlA4PiEQvF2= NUfafpZsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
HCC1954 NWWyZ3Q{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWHJR|UxRTR6LkG3NFQh|ryP MkPQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OTh|Nz:nQnNCVkeHUkyvZV4>
FADU MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1r0UGlEPTB;NEiuN|A{OSEQvF2= NGn0V3c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTdzOEO3M{c,W0GQR1XSQE9iRg>?
S-117 Mn7oS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUjJR|UxRTR6LkO4NVUh|ryP NUP0coJkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
LS-1034 NY\1eGtNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVvJR|UxRTR6LkewOlch|ryP NYTqZnVSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
CAMA-1 NIHPRZFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYXJR|UxRTR7LkW1OFMh|ryP NFnXcVE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTdzOEO3M{c,W0GQR1XSQE9iRg>?
LU-134-A MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkfYTWM2OD12OT64NFg2KM7:TR?= NV7ifYU6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
NCI-H1838 NELsT4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NY[xSpkzUUN3ME20PU45ODh5IN88US=> NF\vN3M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTdzOEO3M{c,W0GQR1XSQE9iRg>?
Assay
Methods Test Index PMID
Western blot pSrc / Src / pPlcg / Plcg / pStat5 / Stat5 ; pFGFR1(pY20) / FGFR1 ; cleaved caspase-3 / cleaved caspase-7 / BAX / Bcl-2 ; p-Rb(S807/811) / Rb / CDK4 / CDK6 / Cyclin D1 / CDK2 / Cyclin E1 ; RAD51 ; p-MEK / MEK / p-ERK / ERK ; c-Jun / p-JNK(T183/Y185) / JNK ; p-p38 MAPK / p38 MAPK ; p-JAK2 / JAK2 / p-STAT3 / STAT3 ; PI3K p85 / p-PI3K / p-PDK1 / PDK1 / p-mTOR / mTOR ; p-PDGFRα / PDGFRα ; PARP / Caspase-3 / Active Caspase-3 ; AIF / Cyto C ; Mcl-1 / Survivin / Bcl-Xl / XIAP / Bax / Bcl-2 / Bim ; β-catenin ; β-catenin ; ABL 22781593 30959969 24472312 19878872
Growth inhibition assay Cell viability 30174789
In vivo In a mouse xenograft model of Ba/F3 cells expressing native Bcr-Abl, AP24534 (2.5 mg/kg and 5 mg/kg) prolongs mice median survival. In the xenograft model of Ba/F3 Bcr-AblT315I, AP24534 (10 mg/kg–50 mg/kg) significantly suppresses tumor growth. AP24534 (30 mg/kg) decreases the phosphorylated Bcr-Abl and phosphorylated CrkL levels in the tumors. [2]

Protocol (from reference)

Kinase Assay:[1]
  • Peptide substrate phosphorylation assays with GST-Abl kinase domains:

    The effect of AP24534 (0-320 nM) on GST-Abl kinase activity is assessed by using a synthetic peptide substrate (Abltide: EAIYAAPFAKKK). Assays are carried out at 30 °C for 15 min in 25 μL reaction mixture: 8 mM MOPS (pH 7), 0.2 mM EDTA, 50 μM Abltide, 30 mM MgCl2, 10 mM β-glycerol phosphate, 1 mM EGTA, 0.002% Brij-35, 0.4 mM DTT, 0.2 mg/mL BSA, 0.4 mM sodium orthovanadate, 10 nM WT or mutant GST-Abl kinase, and 100 µM ATP/γ-32[P]ATP (5000 cpm/pmol). Reactions are terminated by transferring a portion of the reaction mixture onto a p81 phosphocellulose filter and immersing in 0.75% phosphoric acid. Filters are washed 3 times in 0.75% phosphoric acid, rinsed in acetone, and air dried; phosphate incorporation is determined by scintillation counting. All results are corrected for background binding to the filters, as determined by omitting peptide substrate from the kinase reaction. Time course experiments to establish the linear range of enzymatic activity precedes kinase assays.

Cell Research:[2]
  • Cell lines: Ba/F3 cells expressing Bcr-Abl or a range of single mutations in the kinase domain of Bcr-Abl
  • Concentrations: 0-625 nM
  • Incubation Time: 72 hours
  • Method: Ba/F3 cell lines are distributed in 96-well plates (4 × 103 cells/well) and incubated with AP24534 for 72 hours. Proliferation is measured using a methanethiosulfonate (MTS)-based viability assay (CellTiter96 Aqueous One Solution). All values are normalized to the control wells with no drug. IC50 values are reported as the mean of three independent experiments performed in quadruplicat
  • (Only for Reference)
Animal Research:[1]
  • Animal Models: Mouse xenograft models of Ba/F3 cells expressing Bcr-Abl or Bcr-AblT315I
  • Dosages: 2.5 mg/kg and 5 mg/kg for Ba/F3 Bcr-Abl; 2.5 mg/kg–50 mg/kg for Ba/F3 Bcr-AblT315I
  • Administration: Oral gavage once daily
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 30 mg/mL
(56.33 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
1% CMC Na
For best results, use promptly after mixing.

30mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 532.56
Formula

C29H27F3N6O

CAS No. 943319-70-8
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=C(C=C(C=C1)C(=O)NC2=CC(=C(C=C2)CN3CCN(CC3)C)C(F)(F)F)C#CC4=CN=C5N4N=CC=C5

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04554459 Recruiting Drug: Ponatinib 15 MG Oral Tablet Acute Lymphoblastic Leukemia Adult|Ph+ ALL|Newly Diagnosed Institute of Hematology and Blood Transfusion Czech Republic|CZECRIN - Czech Clinical Research Infrastructure Network February 16 2021 Phase 2
NCT04160546 Recruiting Drug: Ponatinib 15 MG|Drug: Acetylsalicylic acid 100 MG Chronic Myeloid Leukemia Chronic Phase Fundacion CRIS de Investigación para Vencer el Cáncer|Incyte Biosciences UK|Apices Soluciones S.L. January 17 2020 Phase 2
NCT03934372 Active not recruiting Drug: Ponatinib Acute Myeloid Leukemia|Accelerated Phase Chronic Myeloid Leukemia|Blast Phase Chronic Myeloid Leukemia|Chronic Phase Chronic Myeloid Leukemia|Acute Lymphoblastic Leukemia|Acute Lymphocytic Leukemia|Leukemia|Lymphoma|Solid Tumors Incyte Biosciences International Sàrl|Incyte Corporation January 29 2020 Phase 1|Phase 2
NCT03690115 Recruiting Drug: Ponatinib 30 MG Leukemia Myeloid Acute Versailles Hospital December 2 2019 Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
Is the pre-solubilized inhibitor suitable for in vivo whole animal studies? Whether the solvent contains any non-DMSO stabilizer?

Answer:
Our 10mM Ponatinib in DMSO solution is in pure DMSO and there is not other stabilizer added. You can use it for animal study. The vehicle we suggest for Ponatinib is: 30% PEG400/0.5% Tween80/5% Propylene glycol. It is a milky suspension used for oral gavage.

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