Ponatinib
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MedKoo CAT#: 202320

CAS#: 943319-70-8 (free base)

Description: Ponatinib is an orally bioavailable multitargeted receptor tyrosine kinase (RTK) inhibitor with potential antiangiogenic and antineoplastic activities. Multitargeted tyrosine kinase inhibitor AP24534 inhibits unmutated and all mutated forms of Bcr-Abl, including T315I, the highly drug therapy-resistant missense mutation of Bcr-Abl. This agent also inhibits other tyrosine kinases including those associated with vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs); in addition, it inhibits the tyrosine kinase receptor TIE2 and FMS-related tyrosine kinase receptor-3 (Flt3).


Price and Availability

Size
Price

100mg
USD 90
1g
USD 550
10g
USD 2750
Size
Price

200mg
USD 150
2g
USD 950
20g
USD 4650
Size
Price

500mg
USD 350
5g
USD 1750
50g
Ask price

Ponatinib free base, purity > 98%, is in stock. The same day shipping out after order is received. Delivery time: overnight (USA/Canada); 3-5 days (worldwide). Shipping fee: from $30.00 (USA); from $45.00 (Canada); from $70.00 (international). Note: the estimated shipping out time for order > 2g may be 2 weeks.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 202320
Name: Ponatinib
CAS#: 943319-70-8 (free base)
Chemical Formula: C29H27F3N6O
Exact Mass: 532.21984
Molecular Weight: 532.56
Elemental Analysis: C, 65.40; H, 5.11; F, 10.70; N, 15.78; O, 3.00


Related CAS #: 943319-70-8 (free base)   1114544-31-8 (HCl)   1232836-25-7 (tris-hydrochloride)    

Synonym: AP24534; AP-24534; AP 24534; Ponatinib. Brand name: Iclusig.

IUPAC/Chemical Name: 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide.

InChi Key: PHXJVRSECIGDHY-UHFFFAOYSA-N

InChi Code: InChI=1S/C29H27F3N6O/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39)

SMILES Code: O=C(NC1=CC=C(CN2CCN(C)CC2)C(C(F)(F)F)=C1)C3=CC=C(C)C(C#CC4=CN=C5C=CC=NN54)=C3


Technical Data

Appearance:
white solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Certificate of Analysis:

Safety Data Sheet (MSDS):

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Ponatinib free base is soluble in DMSO at 50 mg/mL; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water. The solubility of ponatinib in pH 1.7, 2.7, and 7.5 buffers is 7790 mcg/ml, 3.44 mcg/ml, and 0.16 mcg/ml, respectively, indicating a decrease in solubility with increasing pH.

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

Ponatinib was approved ion 2012, but temporarily suspended sales on 31 October 2013 because of "the risk of life-threatening blood clots and severe narrowing of blood vessels". This suspension was partially lifted


References

1: Oaxaca DM, Yang-Reid SA, Ross JA, Rodriguez G, Staniswalis JG, Kirken RA. Sensitivity of imatinib-resistant T315I BCR-ABL CML to a synergistic combination of ponatinib and forskolin treatment. Tumour Biol. 2016 Jul 21. [Epub ahead of print] PubMed PMID: 27444277.

2: Dessilly G, Panin N, Elens L, Haufroid V, Demoulin JB. Impact of ABCB1 1236C > T-2677G > T-3435C > T polymorphisms on the anti-proliferative activity of imatinib, nilotinib, dasatinib and ponatinib. Sci Rep. 2016 Jul 12;6:29559. doi: 10.1038/srep29559. PubMed PMID: 27405085; PubMed Central PMCID: PMC4941718.

3: Abid MB, De Mel S. Does ponatinib cross the blood-brain barrier? Br J Haematol. 2016 Jun 28. doi: 10.1111/bjh.14222. [Epub ahead of print] PubMed PMID: 27352067.

4: Breccia M, Abruzzese E, Iurlo A, Gozzini A, Isidori A, Gangemi D, Pregno P, Alimena G. Efficacy and safety of second-line ponatinib after failure of a single previous tyrosine kinase inhibitor for chronic myeloid leukemia patients in chronic phase. Haematologica. 2016 Jun;101(6):e267-8. doi: 10.3324/haematol.2016.145623. Epub 2016 May 31. PubMed PMID: 27252515.

5: Engel NW, Constantin A, Fowlkes S, Assouline S. Unexpected Success of Watch and Wait Strategy in a Ponatinib-Intolerant Patient With Chronic Myeloid Leukemia. J Oncol Pract. 2016 Jun;12(6):592-4. doi: 10.1200/JOP.2016.012054. Epub 2016 May 31. PubMed PMID: 27246687.

6: Sparidans RW, Kort A, Schinkel AH, Schellens JH, Beijnen JH. Liquid chromatography-tandem mass spectrometric assay for ponatinib and N-desmethyl ponatinib in mouse plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jun 15;1023-1024:24-9. doi: 10.1016/j.jchromb.2016.04.049. Epub 2016 May 2. PubMed PMID: 27179188.

7: Matsuda Y, Yamauchi T, Hosono N, Uzui K, Negoro E, Morinaga K, Nishi R, Yoshida A, Kimura S, Maekawa T, Ueda T. Combination of panobinostat with ponatinib synergistically overcomes imatinib-resistant CML cells. Cancer Sci. 2016 Jul;107(7):1029-38. doi: 10.1111/cas.12965. Epub 2016 Jun 21. PubMed PMID: 27166836; PubMed Central PMCID: PMC4946706.

8: Narasimhan NI, Dorer DJ, Davis J, Turner CD, Sonnichsen D. Evaluation of the effect of multiple doses of rifampin on the pharmacokinetics and safety of ponatinib in healthy subjects. Clin Pharmacol Drug Dev. 2015 Sep;4(5):354-60. doi: 10.1002/cpdd.182. Epub 2015 May 1. PubMed PMID: 27137144.

9: Lipton JH, Chuah C, Guerci-Bresler A, Rosti G, Simpson D, Assouline S, Etienne G, Nicolini FE, le Coutre P, Clark RE, Stenke L, Andorsky D, Oehler V, Lustgarten S, Rivera VM, Clackson T, Haluska FG, Baccarani M, Cortes JE, Guilhot F, Hochhaus A, Hughes T, Kantarjian HM, Shah NP, Talpaz M, Deininger MW; EPIC investigators. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2016 May;17(5):612-21. doi: 10.1016/S1470-2045(16)00080-2. Epub 2016 Apr 12. PubMed PMID: 27083332.

10: Fava C, Saglio G. Ponatinib for chronic myeloid leukaemia: future perspectives. Lancet Oncol. 2016 May;17(5):546-7. doi: 10.1016/S1470-2045(16)30064-X. Epub 2016 Apr 12. PubMed PMID: 27083331.

11: Tournaire G, Despas F, Huguet F, Montastruc JL, Bondon-Guitton E. Peripheral arterial occlusive disease during ponatinib therapy after failure of imatinib: a case report. J Clin Pharm Ther. 2016 Jun;41(3):360-361. doi: 10.1111/jcpt.12383. Epub 2016 Mar 23. PubMed PMID: 27009771.

12: Breccia M, Colafigli G, Quattrocchi L, Abruzzese E, Alimena G. Cutaneous Lesions Anticipating Accelerated Phase of Multidrug Resistant Chronic Myeloid Leukemia Responsive to Ponatinib. Mediterr J Hematol Infect Dis. 2016 Feb 20;8(1):e2016016. doi: 10.4084/MJHID.2016.016. eCollection 2016. PubMed PMID: 26977275; PubMed Central PMCID: PMC4771144.

13: Darwish HW, Bakheit AH, Abdelhameed AS, AlKhairallah AS. Micellar Enhanced Spectrofluorimetric Method for the Determination of Ponatinib in Human Plasma and Urine via Cremophor RH 40 as Sensing Agent. Int J Anal Chem. 2015;2015:210503. doi: 10.1155/2015/210503. Epub 2015 Dec 31. PubMed PMID: 26880920; PubMed Central PMCID: PMC4736017.

14: Saglio G, Fava C. BCR-ABL1 mutation ≠ ponatinib resistance. Blood. 2016 Feb 11;127(6):666-7. doi: 10.1182/blood-2015-12-685149. PubMed PMID: 26869304.

15: Kang Z, Ji Y, Zhang G, Qu Y, Zhang L, Jiang W. Ponatinib attenuates experimental pulmonary arterial hypertension by modulating Wnt signaling and vasohibin-2/vasohibin-1. Life Sci. 2016 Mar 1;148:1-8. doi: 10.1016/j.lfs.2016.02.017. Epub 2016 Feb 6. PubMed PMID: 26860892.

16: Ponatinib. Aust Prescr. 2015 Dec;38(6):221-2. Epub 2015 Sep 18. Review. PubMed PMID: 26843719; PubMed Central PMCID: PMC4674036.

17: Sidaway P. Haematological cancer: Ponatinib in CML - keeping PACE with multiple mutations. Nat Rev Clin Oncol. 2016 Mar;13(3):135. doi: 10.1038/nrclinonc.2016.13. Epub 2016 Feb 2. PubMed PMID: 26831184.

18: Parker WT, Yeung DT, Yeoman AL, Altamura HK, Jamison BA, Field CR, Hodgson JG, Lustgarten S, Rivera VM, Hughes TP, Branford S. The impact of multiple low-level BCR-ABL1 mutations on response to ponatinib. Blood. 2016 Apr 14;127(15):1870-80. doi: 10.1182/blood-2015-09-666214. Epub 2016 Jan 14. PubMed PMID: 26773037; PubMed Central PMCID: PMC4832506.

19: Quilot FM, Georges M, Favrolt N, Beltramo G, Foignot C, Grandvuillemin A, Montani D, Bonniaud P, Camus P. Pulmonary hypertension associated with ponatinib therapy. Eur Respir J. 2016 Feb;47(2):676-9. doi: 10.1183/13993003.01110-2015. Epub 2016 Jan 7. PubMed PMID: 26743481.

20: Breccia M, Alimena G. Ponatinib in chronic myeloid leukaemia: ready for first-line? Lancet Haematol. 2015 Sep;2(9):e352-3. doi: 10.1016/S2352-3026(15)00130-1. Epub 2015 Jul 30. PubMed PMID: 26685767.