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Product Data Sheet
Product Name:Cat. No.:
Ponatinib (AP24534)GC14396
Chemical Properties
Cas No.ChemicalNameCanonicalSMILESFormulaSolubilityGeneraltipsShippingCondition
943319-70-8
3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide
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=C5C29H27F3N6O
≥53.3mg/mL in DMSO, <2.45mg/mL in EtOH, <2.31 mg/mLin H2O
M.WtStorage
532.56Store at -20°C
For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in theultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.Evaluation sample solution : ship with blue ice All other available size: ship with RT , orblue ice upon request.
Structure
Caution: Producthasnot been fully validated for medical applications. For research use only.
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实验参考方法
Cell experiment: [1]Cell linesBaF3 cells stably expressing ZMYM2-FGFR1 and CEP110-FGFR1 or BCR-FGFR1
The solubility of this compound in DMSO is >10 mM. General tips for obtaining ahigher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake
Preparation method
it in the ultrasonic bath for a while.Stock solution can be stored below -20°C forseveral months.
Reaction Conditions48 hours, 50 nM for BaF3-ZMYM2, BAF3-CEP 100 nM for BaF3-BCR
Ponatinib treatment reduced phosphorylation FGFR1 levels. The percentage ofcells in S-phase was also dramatically decreased, while the percentage of
Applications
apoptotic cells was increased in the three different chimeric kinase-transformedBaF3 cells which suggested that their survival depended on activated FGFR1.
Animal experiment: [2]Animal modelsFemale CB.17 severe combined immunodeficient mice injected with MV4-11 cellsDosage formOral administration, 1–25 mg/kg, once daily for 4 weeks
Ponatinib potently inhibited tumor growth in a dose-dependent manner.
Administration of 1 mg/kg, the lowest dose tested, led to significant inhibition oftumor growth (TGI = 46%, P < 0.01) and doses of 2.5 mg/kg or greater resulted
Applications
in tumor regression. Notably, dosing with 10 or 25 mg/kg led to complete anddurable tumor regression with no palpable tumors detected during a 31-dayfollow up.
Please test the solubility of all compounds indoor, and the actual solubility may
Other notesslightly differ with the theoretical value. This is caused by an experimental
system error and it is normal.
References:
[1] Ren M, Qin H, Ren R, Cowell JK. Ponatinib suppresses the development of myeloid and lymphoidmalignancies associated with FGFR1 abnormalities. Leukemia. 2013 Jan;27(1):32-40.
[2] Gozgit JM, Wong MJ, Wardwell S, Tyner JW, Loriaux MM, Mohemmad QK, Narasimhan NI,
Shakespeare WC, Wang F, Druker BJ, Clackson T, Rivera VM. Potent activity of ponatinib (AP24534) inmodels of FLT3-driven acute myeloid leukemia and other hematologic malignancies. Mol Cancer Ther.2011 Jun;10(6):1028-35.
Background
BCR-ABL fusion gene forms when the ABL gene from chromosome 9 joins to the BCR gene onchromosome 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
Caution: Producthasnot been fully validated for medical applications. For research use only.
Tel: (626) 353-8530 Fax: (626) 353-8530 E-mail: tech@glpbio.com
Address: 10292 Central Ave. #205, Montclair, CA, USA
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Product Data Sheet
gene is found in most patients with chronic myelogenous leukemia (CML), and in some patients withacute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML).
Ponatinib is the second-generation pan inhibitor of BCR-Abl kinases, which is also effective against themutant form of BCR-Abl (T315I). [1, 2] IC50 for WT and mutant form are 0.5 and 11 nM. [4] Ponatinib alsoinhibits several other clinically relevant kinases (RET, FLT3, KIT, PDGFRα, PDGFRβ, and FGFR1) invitro, with IC50s of 5, 25, 100, 5, 9, and 23) in Ba/F3 cells lines. [4]
References:
1. Huang WS, Metcalf CA, Sundaramoorthi R, Wang Y, Zou D, Thomas RM, Zhu X, Cai L, Wen D, Liu S,Romero J, Qi J, Chen I, Banda G, Lentini SP, Das S, Xu Q, Keats J, Wang F, Wardwell S, Ning Y,
Snodgrass JT, Broudy MI, Russian K, Zhou T, Commodore L, Narasimhan NI, Mohemmad QK, Iuliucci J,Rivera VM, Dalgarno DC, Sawyer TK, Clackson T, Shakespeare WC (June 2010). Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl) methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpointcluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant. J. Med. Chem. 53(12): 4701–19.
2. O'Hare T, Pollock R, Stoffregen EP, Keats JA, Abdullah OM, Moseson EM, Rivera VM, Tang H, MetcalfCa CA, Bohacek RS, Wang Y, Sundaramoorthi R, Shakespeare WC, Dalgarno D, Clackson T, Sawyer TK,Deininger MW, Druker BJ (2004). Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML. Blood 104 (8): 2532–2539.
3. Cilloni D and Saglio G. Molecular pathways: BCR-ABL. Clinical Cancer Res (2011) 18(4):930-9374. Gozgit JM, Wong MJ, Zhu X, Schrock AB, Chen T, Clackson T and Rivera VM. Ponatinib, a potent pan-BCR-ABL inhibitor, retains activity against gatekeeper mutants of FLT3, RET, KIT, PDGFR α/β andFGFR1. 2012 AACR poster.
Caution: Producthasnot been fully validated for medical applications. For research use only.
Tel: (626) 353-8530 Fax: (626) 353-8530 E-mail: tech@glpbio.com
Address: 10292 Central Ave. #205, Montclair, CA, USA
3www.glpbio.com
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