Ibrutinib

featured

WARNING: This product is for research use only, not for human or veterinary use.

Description:Ibrutinib, also known as PCI-32765, is a potent and orally active BTK inhibitor. Ibrutinib binds to and inhibits BTK activity, preventing B-cell activation and B-cell-mediated signaling and inhibiting the growth of malignant B cells that overexpress BTK. Ibrutinib was approved by the US FDA on November 13, 2013 for the treatment of mantle cell lymphoma.

Price and Availability

Ibrutinib (PCI-32765), purity > 98%,is in stock. The same day shipping after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 202171Name: IbrutinibCAS#: 936563-96-1Chemical Formula: C25H24N6O2Exact Mass: 440.19607Molecular Weight: 440.49706Elemental 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

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 thetreatment of chronic lymphocytic leukemia. Expert Rev Hematol. 2013Oct;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 chroniclymphocytic 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 chroniclymphocytic 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 chroniclymphocytic 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 tyrosinekinase is commonly overexpressed in mantle cell lymphoma and itsattenuation by Ibrutinib induces apoptosis. Leuk Res. 2013Oct;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 BTKinhibitors in clinical development. J Hematol Oncol. 2013 Aug 19;6:59.doi: 10.1186/1756-8722-6-59. PubMed PMID: 23958373; PubMed CentralPMCID: PMC3751776.

7: Chang BY, Francesco M, De Rooij MF, Magadala P, Steggerda SM, HuangMM, Kuil A, Herman SE, Chang S, Pals ST, Wilson W, Wiestner A,Spaargaren M, Buggy JJ, Elias L. Egress of CD19(+)CD5(+) cells intoperipheral blood following treatment with the Bruton tyrosine kinaseinhibitor ibrutinib in mantle cell lymphoma patients. Blood. 2013 Oct3;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 lymphocyticleukemia. 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, ZhongY, 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 anirreversible molecular inhibitor of ITK driving a Th1-selective pressurein 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, GrantB, Sharman JP, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA,Johnson AJ, Sukbuntherng J, Chang BY, Clow F, Hedrick E, Buggy JJ, JamesDF, O"Brien S. Targeting BTK with ibrutinib in relapsed chroniclymphocytic leukemia. N Engl J Med. 2013 Jul 4;369(1):32-42. doi:10.1056/NEJMoa1215637. Epub 2013 Jun 19. PubMed PMID: 23782158; PubMedCentral PMCID: PMC3772525.