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Ponatinib

Ponatinib is a tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia and acute lymphoblastic leukemia.
It targets the BCR-ABL fusion protein and is effective against multiple drug-resistant variants of the protein.
Ponatinib has been approved for use in patients with chronic myeloid leukemia who are resistant to or intolerant of other tyrosine kinase inhibitors.
Research on Ponatinib is ongoing to optimize its use and identify the best protocols and products for reproducibility and accuracy.
PubCompare.ai can help researchers streamline thir Ponatinib research workflow by leveraging AI to locate relevant protocols from literature, preprints, and patents, and compare them to identify the most effective approaches.

Most cited protocols related to «Ponatinib»

Ex vivo functional drug screens were performed on freshly isolated mononuclear cells from AML samples. Briefly, 10,000 cells per well were arrayed into three, 384-well plates containing 122 small-molecule inhibitors. This panel contained graded concentrations of a drugs with activity against two-thirds of the tyrosine kinome as well as other non-tyrosine kinase pathways, including mitogen activated protein kinases (MAPKs), phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT serine/threonine kinase 1/mechanistic target of rapamycin kinase (PIK3C/AKT/MTOR), protein kinase AMP-activated (AMPK/PRKAA), ATM serine/threonine kinase (ATM), Aurora kinases, calcium/calmodulin dependent protein kinases (CAMKs), cyclin-dependent kinases (CDKs), serine/threonine protein kinase 3 (GSK3), I-kappaB kinase (IKK), cAMP dependent protein kinase (PKA), protein kinase C (PKC), polo-like kinase 1 (PLK1), and RAF proto-oncogene serine/threonine kinase (RAF). In addition, the library contained small molecule inhibitors with activity against the BCL2 family, bromodomain containing 4 (BRD4), Hedgehog, heat shock protein 90 (HSP90), NOTCH/gamma-secretase, proteasome, survivin, signal transducer and activator of transcription 3 (STAT3), histone deacetylase (HDAC), and WNT/beta-catenin. Drug plates were created using inhibitors purchased from LC Laboratories and Selleck Chemicals and master stocks were reconstituted in dimethyl sulfoxide (DMSO) and stored at −80 °C. Master plates were created by distributing a single agent per well in a seven-point concentration series, created from three-fold dilutions of the most concentrated stock resulting in a range pf 10 μM to 0.0137 μM for each drug (except dasatinib, ponatinib, sunitinib, and YM-155 which were plated at a concentration range of 1 μM to 0.00137 μM). DMSO control wells and positive control wells containing a drug combination of Flavopiridol, Staurosporine and Velcade were placed on each plate, with the final concentration of DMSO ≤0.1% in all wells. Daughter plates were created using a V&P Scientific 384-well pin tool head operated by the Caliper Sciclone ALH 3000 and equipped with 0.457mm diameter, 30 nanoliter, slotted stainless steel pins (cat num: FP1NS30). Daughter and destination plates were sealed with pealable thermal seals using a PlateLoc thermal sealer. Destination plates were stored at −20 °C for no more than three months and thawed immediately before use. Primary mononuclear cells were plated across single-agent inhibitor panels within 24 h of collection. Cells were seeded into 384-well assay plates at 10,000 cells per well in Roswell Park Memorial Institute (RPMI) 1640 media supplemented with fetal bovine serum (FBS) (10%), l-glutamine, penicillin/streptomycin, and β-mercaptoethanol (10−4 M). After 3 d of culture at 37 °C in 5% CO2, MTS reagent (CellTiter96 AQueous One; Promega) was added, optical density was measured at 490 nm, and raw absorbance values were adjusted to a reference blank value and then used to determine cell viability (normalized to untreated control wells).
Publication 2018
Ex vivo functional drug screens were performed on freshly isolated mononuclear cells from AML samples. Briefly, 10,000 cells per well were arrayed into three, 384-well plates containing 122 small-molecule inhibitors. This panel contained graded concentrations of a drugs with activity against two-thirds of the tyrosine kinome as well as other non-tyrosine kinase pathways, including mitogen activated protein kinases (MAPKs), phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT serine/threonine kinase 1/mechanistic target of rapamycin kinase (PIK3C/AKT/MTOR), protein kinase AMP-activated (AMPK/PRKAA), ATM serine/threonine kinase (ATM), Aurora kinases, calcium/calmodulin dependent protein kinases (CAMKs), cyclin-dependent kinases (CDKs), serine/threonine protein kinase 3 (GSK3), I-kappaB kinase (IKK), cAMP dependent protein kinase (PKA), protein kinase C (PKC), polo-like kinase 1 (PLK1), and RAF proto-oncogene serine/threonine kinase (RAF). In addition, the library contained small molecule inhibitors with activity against the BCL2 family, bromodomain containing 4 (BRD4), Hedgehog, heat shock protein 90 (HSP90), NOTCH/gamma-secretase, proteasome, survivin, signal transducer and activator of transcription 3 (STAT3), histone deacetylase (HDAC), and WNT/beta-catenin. Drug plates were created using inhibitors purchased from LC Laboratories and Selleck Chemicals and master stocks were reconstituted in dimethyl sulfoxide (DMSO) and stored at −80 °C. Master plates were created by distributing a single agent per well in a seven-point concentration series, created from three-fold dilutions of the most concentrated stock resulting in a range pf 10 μM to 0.0137 μM for each drug (except dasatinib, ponatinib, sunitinib, and YM-155 which were plated at a concentration range of 1 μM to 0.00137 μM). DMSO control wells and positive control wells containing a drug combination of Flavopiridol, Staurosporine and Velcade were placed on each plate, with the final concentration of DMSO ≤0.1% in all wells. Daughter plates were created using a V&P Scientific 384-well pin tool head operated by the Caliper Sciclone ALH 3000 and equipped with 0.457mm diameter, 30 nanoliter, slotted stainless steel pins (cat num: FP1NS30). Daughter and destination plates were sealed with pealable thermal seals using a PlateLoc thermal sealer. Destination plates were stored at −20 °C for no more than three months and thawed immediately before use. Primary mononuclear cells were plated across single-agent inhibitor panels within 24 h of collection. Cells were seeded into 384-well assay plates at 10,000 cells per well in Roswell Park Memorial Institute (RPMI) 1640 media supplemented with fetal bovine serum (FBS) (10%), l-glutamine, penicillin/streptomycin, and β-mercaptoethanol (10−4 M). After 3 d of culture at 37 °C in 5% CO2, MTS reagent (CellTiter96 AQueous One; Promega) was added, optical density was measured at 490 nm, and raw absorbance values were adjusted to a reference blank value and then used to determine cell viability (normalized to untreated control wells).
Publication 2018
All three compounds have been previously co-crystallized with other class III receptor tyrosine kinases (PLX3397 in CSF1R, sorfenib in KDR, and ponatinib in KIT). Given the high degree of homology between these kinases and FLT3, we expect these inhibitors will exhibit the same overall binding modes. For each inhibitor, we performed structural alignment between the known co-structure containing the inhibitor and the co-structure of FLT3-quizartinib with an emphasis on optimal registration of ATP-binding apparatus. The pose of the inhibitor was then “copied” from its co-structure with another kinase and “pasted” into FLT3 to replace quizartinib. One round of energy minimization using the default parameter of MOE (Chemical Computing Group, Montreal, Quebec, Canada H3A 2R7) was used to refine the structural model.
Publication 2015
FLT3 protein, human Gene, c-fms inhibitors Phosphotransferases PLX3397 ponatinib quizartinib Receptor Protein-Tyrosine Kinases
The primary objective of this phase 1 trial was to determine the maximum tolerated dose or a recommended dose of oral ponatinib administered once daily. Secondary objectives included safety, antileukemia activity, pharmacokinetics, pharmacodynamics, and potential pharmacogenomic markers. For the dose-escalation portion of the study, patients were assigned to cohorts of at least three patients. Dose escalations in the same patient were allowed up to the dose immediately preceding the highest studied dose, without exceeding the maximum tolerated dose, which was defined as the dose at which a dose-limiting toxic effect occurred in no more than one in six patients.25 (link) Treatment was continued until disease progression, an adverse event leading to cessation, withdrawal of consent, or investigator discretion (Appendix B in the Supplementary Appendix).
Publication 2012
Disease Progression Drug Kinetics Patients ponatinib Safety
The efficacy population included all 444 patients who were assigned to a cohort. The safety population included all 449 patients who received 1 or more doses of ponatinib. The planned sample sizes for the cohorts were estimated to rule out prespecified null response rates with the use of 95% confidence intervals as specified in Appendix B in the Supplementary Appendix. Two-sided, exact 95% confidence intervals were calculated for rates of a major cytogenetic response, major hematologic response, complete hematologic response, and major molecular response. The duration of response, progression-free survival, and overall survival were estimated with the use of the Kaplan–Meier method. Fisher’s exact test was used for subgroup comparisons.
Publication 2013
Patients ponatinib Safety

Most recents protocols related to «Ponatinib»

Ponatinib monohydrochloride (501 mg, 0.88 mmol) was weighed into a round bottom flask, to which was added acetonitrile (5.0 mL) and formic acid (0.35 mL). The resulting suspension was placed in an oil bath at 50 °C. After stirring for 1 h, water (0.50 mL) was added. Immediate dissolution was observed, the resulting yellow solution was filtered while hot, and subsequently allowed to cool to room temperature (RT) over a 1.5 h period. Precipitation was observed after 2 h at RT. The suspension was stirred for an additional 16 h. The solids were collected by filtration, washed with cold acetonitrile (2.0 mL), and dried in a vacuum oven at RT to give pon·HCl as a yellow solid (248 mg, 50% yield).
Publication 2024
The LRRK2–ponatinib dataset was collected similarly, except for the following differences. Movies were recorded at defocus values from –0.6 to –1.8 μm at a magnification of 130 kx in hardware binning mode, corresponding to a pixel size of 0.6485 Å at the specimen. During 2.0 s exposure, 60 frames were collected with a total electron dose of ~68 e–2 (at a dose rate of 1.1 e/frame/Å2). In total, 27,611 images were collected. Motion correction was performed on hardware-binned movie stacks and binned by 1 using MotionCor242 (link). CTF estimation was performed using Gctf43 (link). After the selection of high-quality micrographs, 24,254 images were used during the data process.
The LRRK2–ponatinib dataset was processed similarly in cryoSPARC. Briefly, particles were selected using the template picker and extracted using a binning factor of 4. Several rounds of the 2D classification were performed and two groups of good classes were observed, corresponding to the LRRK2 monomer and dimer states, respectively. Both groups were selected, and ab initio reconstruction was performed. Heterogeneous refinement was performed to further separate the LRRK2 monomer and dimer states. As a result, 95,805 particles were assigned to the monomer class and 75,849 particles to the dimer. Both 3D classes were further refined after extraction of unbinned particles corresponding to each identified sub-set. For the LRRK2 monomer state, we performed a standard NU-refinement without imposing symmetry. For the LRRK2 dimer state, we performed NU-refinement by applying C2 symmetry, and then symmetry expansion followed by focused refinement to further improve the resolution of each LRRK2 protomer without N-terminal ARM domain. All resolution estimates were calculated according to the gold-standard FSC using the 0.143 criterion45 (link). Local resolution was estimated in cryoSPARC. The density maps were B-factor sharpened in cryoSPARC and used to produce figures and build models.
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Publication 2024
For our experiments, HCAEC line, cell culturing medium, trypsin-EDTA, Hank’s balanced salt solution (HBSS) and dimethyl-sulfoxide (DMSO) were obtained from Sigma-Aldrich (St. Louis, MO, USA). Plastic cell culturing flasks and plates were purchased from Greiner Bio-One (Nürtingen, Germany). Ponatinib was ordered from Cayman Chemical (Ann Arbor, MI, USA). HCAECs were cultured in MesoEndo growth medium in 75 cm2 flasks at 5% CO2 and 80% humidity. When the cells reached 80–90% confluence in the flask, they were plated in 6-well culture plates (105 cells/well), and after 2 days, the cells were treated for up to 48 h with clinically relevant and supratherapeutic concentrations of Ponatinib. The final concentrations of Ponatinib were 50, 150, and 1000 nM, DMSO (0.2 v/v %) was used as a negative control, and tumor necrosis factor alpha (TNF-α) (100 ng/mL; Gibco, Waltham, MA, USA) was used as a positive control. After the treatments, the cells were collected from both the plate and the culture medium.
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Publication 2024
Crystals of pon·HCl suitable for analysis by single-crystal X-ray diffraction (SCXRD) were grown in an unconventional manner. Ponatinib freebase was added to a 4 mL vial, and acetonitrile was added on top of the solid material until covered. 1 mL of a solution prepared from acetonitrile (10 mL), formic acid (0.7 mL), water (0.8 mL), and hydrochloric acid (concentrated, 0.2 mL) was then layered over the first acetonitrile solution in the vial. After two days at RT, both white needle and yellow block crystals were seen in the vial. The crystals were carefully separated using the Pasteur method, and PXRD data were acquired for each type of crystal. The yellow block crystals were found to be pon·HCl, and the white needles were found to be the previously reported ponatinib monohydrochloride.69,70
Publication 2024
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Cell culture medium 199 (M199) was from Lonza (Verviers, Belgium). Recombinant human VEGF-165 was purchased from R&D Systems, Inc. (Minneapolis, MN, USA). Human plasma fibrinogen was acquired from Merck/Millipore (Darmstadt, Germany). Proteinase inhibitor mixture complete, EDTA-free, was purchased from Roche Diagnostics (Mannheim, Germany). Imatinib, nilotinib and ponatinib were from Cayman Chemical (Ann Arbor, MI, USA). All other reagents were from Sigma-Aldrich (Taufkirchen, Germany) unless otherwise stated.
Publication 2024

Top products related to «Ponatinib»

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Ponatinib is a tyrosine kinase inhibitor, a type of laboratory equipment used for research purposes. It functions by inhibiting the activity of certain enzymes involved in cellular signaling pathways.
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Dasatinib is a laboratory reagent used in research applications. It is a tyrosine kinase inhibitor that can be used to study cellular signaling pathways.
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Imatinib is a tyrosine kinase inhibitor. It is a laboratory reagent used in research applications.
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Fetal Bovine Serum (FBS) is a cell culture supplement derived from the blood of bovine fetuses. FBS provides a source of proteins, growth factors, and other components that support the growth and maintenance of various cell types in in vitro cell culture applications.
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Nilotinib is a synthetic chemical compound that functions as a tyrosine kinase inhibitor. It is primarily used in research and laboratory settings to study cellular signaling pathways and biochemical processes.
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DMSO is a versatile organic solvent commonly used in laboratory settings. It has a high boiling point, low viscosity, and the ability to dissolve a wide range of polar and non-polar compounds. DMSO's core function is as a solvent, allowing for the effective dissolution and handling of various chemical substances during research and experimentation.
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RPMI 1640 is a common cell culture medium used for the in vitro cultivation of a variety of cells, including human and animal cells. It provides a balanced salt solution and a source of essential nutrients and growth factors to support cell growth and proliferation.
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Imatinib is a small molecule inhibitor. It is used as a laboratory reagent for research purposes.
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Sunitinib is a small-molecule inhibitor of multiple receptor tyrosine kinases, including vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, platelet-derived growth factor receptors (PDGFR) α and β, stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), and the receptor encoded by the RET proto-oncogene.
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Ponatinib is a tyrosine kinase inhibitor used for research purposes. It inhibits the activity of various kinases, including BCR-ABL, FGFR, PDGFR, and SRC family kinases.

More about "Ponatinib"

Ponatinib is a powerful tyrosine kinase inhibitor (TKI) that has revolutionized the treatment of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL).
This targeted therapy works by inhibiting the BCR-ABL fusion protein, which is a key driver of these blood cancers.
Ponatinib has proven effective against multiple drug-resistant variants of the BCR-ABL protein, making it a crucial option for patients who have become resistant to other TKIs like Imatinib, Dasatinib, and Nilotinib.
Researchers are continuously exploring ways to optimize the use of Ponatinib, including identifying the best protocols and products for reproducibility and accuracy.
Techniques like cell culture, using RPMI 1640 media and fetal bovine serum (FBS), as well as the use of solvents like DMSO, are often employed in Ponatinib research.
By leveraging the power of AI, tools like PubCompare.ai can help streamline the research workflow by locating relevant protocols from the literature, preprints, and patents, and comparing them to find the most effective approaches.
This ongoing research aims to further improve the efficacy and safety of Ponatinib, ultimately benefiting patients with these challenging blood cancers.
As the scientific community continues to push the boundaries of Ponatinib research, we can expect to see even more advancements in the treatment of CML and ALL in the years to come.