Development of the Bruton's tyrosine kinase inhibitor ibrutinib for B cell malignancies.
Ibrutinib is a first-in-class oral covalent inhibitor of Bruton's tyrosine kinase that has demonstrated clinical benefit for many patients with B cell malignancies. Positive results in initial trials led the U.S. Food and Drug Administration to grant ibrutinib three breakthrough therapy designations for mantle cell lymphoma (MCL), del17p chronic lymphocytic leukemia (CLL), and Waldenström's macroglobulinemia (WM). Ibrutinib was approved for these three cancers within 14 months of the original U.S. approval. Additionally, ibrutinib is approved for patient subsets with MCL and/or CLL in >45 other countries. Via a unique mechanism of action, ibrutinib inhibits B cell signaling pathways that regulate the survival, proliferation, adhesion, and homing of cancerous cells. This marks a paradigm shift from the conventional cytotoxic chemotherapy approach to treating B cell malignancies. Ibrutinib continues to be evaluated across a range of B cell malignancies, either as single-agent therapy or in combination with other therapies, and continues to transform the lives of these patients.
Pharmacyclics, Inc, Sunnyvale, California.
Urte
U
Gayko
Janssen Research & Development, LLC, Raritan, New Jersey.
Mann
M
Fung
Pharmacyclics, Inc, Sunnyvale, California.
Fong
F
Clow
Janssen Research & Development, LLC, Raritan, New Jersey.
Steven
S
Sun
Pharmacyclics, Inc, Sunnyvale, California.
Elizabeth
E
Faust
Janssen Research & Development, LLC, Raritan, New Jersey.
Samiyeh
S
Price
Pharmacyclics, Inc, Sunnyvale, California.
Danelle
D
James
Janssen Research & Development, LLC, Raritan, New Jersey.
Margaret
M
Doyle
Pharmacyclics, Inc, Sunnyvale, California.
Samina
S
Bari
Janssen Research & Development, LLC, Raritan, New Jersey.
Sen Hong
SH
Zhuang
D000225:Adenine / Q000031:analogs & derivatives; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000378:metabolism; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine
B cell malignancies; Bruton's tyrosine kinase (BTK) inhibitor; Waldenström's macroglobulinemia; chronic lymphocytic leukemia; ibrutinib; mantle cell lymphoma