MedKoo Cat#: 202171 Name: Ibrutinib CAS#: 936563-96-1 Chemical Formula: C25H24N6O2 Exact Mass: 440.19607 Molecular Weight: 440.49706 Elemental Analysis: C, 68.17; H, 5.49; N, 19.08; O, 7.26

Synonym: PCI32765, PCI-32765, PCI 32765, Ibrutinib, Imbruvica

IUPAC/Chemical Name: (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one.

InChi Key: XYFPWWZEPKGCCK-GOSISDBHSA-N

InChi Code: InChI=1S/C25H24N6O2/c1-2-21(32)30-14-6-7-18(15-30)31-25-22(24(26)27-16-28-25)23(29-31)17-10-12-20(13-11-17)33-19-8-4-3-5-9-19/h2-5,8-13,16,18H,1,6-7,14-15H2,(H2,26,27,28)/t18-/m1/s1

SMILES Code: C=CC(N1C[C@H](N2N=C(C3=CC=C(OC4=CC=CC=C4)C=C3)C5=C(N)N=CN=C52)CCC1)=O

Technical Data

Appearance: white solid powder

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

Certificate of Analysis: View CoA, current batch, lot#TZC41120 View CoA, previous batch: lot#TZC40217 View CoA, previous batch: lot#TZC20130816

QC Data: View QC data: previous batch, lot#TZC40217 View QC date: previous batch, lot#TZC20130816 Ibrutinib 1H-NMR analysis - batch comparison. View QC data: current batch: Lot#TZC41120

Safety Data Sheet (MSDS): View Material 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: Soluble in DMSO at 80 mg / mL, not in water

Shelf Life: >5 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

Ibrutinib is a potent covalent kinase inhibitor that targets BTK. BTK, or Bruton's tyrosine kinase, is an obvious target for therapy of B cell diseases because inactivating mutations lead to B cell aplasia in humans and the disease X-linked agammaglobulinemia. Ibrutinib has modest cytotoxicity against CLL cells in vitro but also blocks trophic stimuli from the microenvironment. As with other inhibitors of the BCR pathway, ibrutinib causes rapid nodal reduction and response associated with rapid increase in lymphocytosis, which then returns to baseline over time. The ORR of ibrutinib in relapsed refractory CLL is 67 % with PFS 88 % at 15 months. In a cohort of untreated patients 65 years and over, the estimated 15 month PFS is 96 %. Registration trials have been initiated, and the difficult task that remains is to determine where in the course of CLL therapy this drug will have the greatest impact and benefit for patients. (source: Curr Hematol Malig Rep. 2013 Mar;8(1):1-6. ).        

References

1: Molica S. The emerging role of ibrutinib in the treatment of chronic lymphocytic leukemia. Expert Rev Hematol. 2013 Oct;6(5):543-6. doi: 10.1586/17474086.2013.831324. Epub 2013 Oct 2. PubMed PMID: 24083545.

2: Rushworth SA, MacEwan DJ, Bowles KM. Ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013 Sep 26;369(13):1277-8. doi: 10.1056/NEJMc1309710#SA2. PubMed PMID: 24066760.

3: Neffendorf JE, Gout I, Hildebrand GD. Ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013 Sep 26;369(13):1277. doi: 10.1056/NEJMc1309710#SA1. PubMed PMID: 24066759.

4: Byrd JC, O'Brien S, James DF. Ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013 Sep 26;369(13):1278-9. doi: 10.1056/NEJMc1309710. PubMed PMID: 24066758.

5: Cinar M, Hamedani F, Mo Z, Cinar B, Amin HM, Alkan S. Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by Ibrutinib induces apoptosis. Leuk Res. 2013 Oct;37(10):1271-7. doi: 10.1016/j.leukres.2013.07.028. Epub 2013 Aug 17. PubMed PMID: 23962569.

6: Akinleye A, Chen Y, Mukhi N, Song Y, Liu D. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol. 2013 Aug 19;6:59. doi: 10.1186/1756-8722-6-59. PubMed PMID: 23958373; PubMed Central PMCID: PMC3751776.

7: Chang BY, Francesco M, De Rooij MF, Magadala P, Steggerda SM, Huang MM, Kuil A, Herman SE, Chang S, Pals ST, Wilson W, Wiestner A, Spaargaren M, Buggy JJ, Elias L. Egress of CD19(+)CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. Blood. 2013 Oct 3;122(14):2412-24. doi: 10.1182/blood-2013-02-482125. Epub 2013 Aug 12. PubMed PMID: 23940282; PubMed Central PMCID: PMC3790509.

8: Jain N, O'Brien S. Ibrutinib (PCI-32765) in chronic lymphocytic leukemia. Hematol Oncol Clin North Am. 2013 Aug;27(4):851-60, x. doi: 10.1016/j.hoc.2013.01.006. PubMed PMID: 23915749.

9: Dubovsky JA, Beckwith KA, Natarajan G, Woyach JA, Jaglowski S, Zhong Y, Hessler JD, Liu TM, Chang BY, Larkin KM, Stefanovski MR, Chappell DL, Frissora FW, Smith LL, Smucker KA, Flynn JM, Jones JA, Andritsos LA, Maddocks K, Lehman AM, Furman R, Sharman J, Mishra A, Caligiuri MA, Satoskar AR, Buggy JJ, Muthusamy N, Johnson AJ, Byrd JC. Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013 Oct 10;122(15):2539-49. doi: 10.1182/blood-2013-06-507947. Epub 2013 Jul 25. PubMed PMID: 23886836; PubMed Central PMCID: PMC3795457.

10: Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, Grant B, Sharman JP, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA, Johnson AJ, Sukbuntherng J, Chang BY, Clow F, Hedrick E, Buggy JJ, James DF, O'Brien S. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013 Jul 4;369(1):32-42. doi: 10.1056/NEJMoa1215637. Epub 2013 Jun 19. PubMed PMID: 23782158; PubMed Central PMCID: PMC3772525.