包装 | 价格(元) |
10mM (in 1mL DMSO) | 电议 |
10mg | 电议 |
50mg | 电议 |
100mg | 电议 |
Cell lines | BaF3 cells stably expressing ZMYM2-FGFR1 and CEP110-FGFR1 or BCR-FGFR1 |
Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. |
Reaction Conditions | 48 hours, 50 nM for BaF3-ZMYM2, BAF3-CEP 100 nM for BaF3-BCR |
Applications | Ponatinib treatment reduced phosphorylation FGFR1 levels. The percentage of cells in S-phase was also dramatically decreased, while the percentage of apoptotic cells was increased in the three different chimeric kinase-transformed BaF3 cells which suggested that their survival depended on activated FGFR1. |
Animal models | Female CB.17 severe combined immunodeficient mice injected with MV4-11 cells |
Dosage form | Oral administration, 1–25 mg/kg, once daily for 4 weeks |
Applications | Ponatinib potently inhibited tumor growth in a dose-dependent manner. Administration of 1 mg/kg, the lowest dose tested, led to significant inhibition of tumor growth (TGI = 46%, P< 0.01) and doses of 2.5 mg/kg or greater resulted in tumor regression. Notably, dosing with 10 or 25 mg/kg led to complete and durable tumor regression with no palpable tumors detected during a 31-day follow up. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
产品描述 | BCR-ABL fusion gene forms when the ABL gene from chromosome 9 joins to the BCR gene on chromosome 22. BCR-ABL is translated into a constitutively active tyrosine kinase, which is oncogenic. Depending on the fusion location, multiple protein variants are formed with molecular weight ranging from 185 to 210 kDa. BCR-ABL activates JAK/STAT pathway and MAPK signaling.[3]This gene is found in most patients with chronic myelogenous leukemia (CML), and in some patients with acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). Ponatinib is the second-generation pan inhibitor of BCR-Abl kinases, which is also effective against the mutant form of BCR-Abl (T315I).[1, 2]IC50 for WT and mutant form are 0.5 and 11 nM.[4]Ponatinib also inhibits several other clinically relevant kinases (RET, FLT3, KIT, PDGFRα, PDGFRβ, and FGFR1) in vitro, with IC50s of 5, 25, 100, 5, 9, and 23) in Ba/F3 cells lines.[4] References: |