Ibrutinib

Ibrutinib
Clinical data
Trade namesImbruvica, others
Other namesPCI-32765, CRA-032765
AHFS/Drugs.comMonograph
MedlinePlusa614007
License data
Pregnancy
category
Routes of
administration
By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding97.3%
MetabolismHepatic (CYP3A & CYP2D6)
Elimination half-life4–6 hours
ExcretionFeces (80%), urine (10%)
Identifiers
  • 1-[(3R)-3-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.232.543 Edit this at Wikidata
Chemical and physical data
FormulaC25H24N6O2
Molar mass440.507 g·mol−1
3D model (JSmol)
  • C=CC(=O)N1CCC[C@H](C1)N2C3=C(C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)C(=NC=N3)N
  • 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
  • Key:XYFPWWZEPKGCCK-GOSISDBHBU

Ibrutinib, sold under the brand name Imbruvica among others, is a small molecule drug that inhibits B-cell proliferation and survival by irreversibly binding the protein Bruton's tyrosine kinase (BTK). Blocking BTK inhibits the B-cell receptor pathway, which is often aberrantly active in B cell cancers. Ibrutinib is therefore used to treat such cancers, including mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström's macroglobulinemia.[6][7] Ibrutinib also binds to C-terminal Src Kinases. These are off-target receptors for the BTK inhibitor. Ibrutinib binds to these receptors and inhibits the kinase from promoting cell differentiation and growth. This leads to many different side effects like left atrial enlargement and atrial fibrillation during the treatment of Chronic Lymphocytic Leukemia.[8]

It is on the World Health Organization's List of Essential Medicines.[9]

  1. ^ "Ibrutinib (Imbruvica) Use During Pregnancy". Drugs.com. 3 December 2019. Retrieved 28 March 2020.
  2. ^ "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  3. ^ "Regulatory Decision Summary for Imbruvica". Drug and Health Products Portal. 4 August 2023. Retrieved 2 April 2024.
  4. ^ "Imbruvica 140 mg Film-Coated Tablets - Summary of Product Characteristics (SmPC)". (emc). 16 January 2020. Retrieved 28 March 2020.
  5. ^ Cite error: The named reference UKlabel2016 was invoked but never defined (see the help page).
  6. ^ a b Cite error: The named reference Imbruvica FDA label was invoked but never defined (see the help page).
  7. ^ a b "Imbruvica EPAR". European Medicines Agency (EMA). 8 July 2021. Retrieved 14 July 2021.
  8. ^ Xiao L, Salem JE, Clauss S, Hanley A, Bapat A, Hulsmans M, et al. (December 2020). "Ibrutinib-Mediated Atrial Fibrillation Attributable to Inhibition of C-Terminal Src Kinase". Circulation. 142 (25): 2443–2455. doi:10.1161/CIRCULATIONAHA.120.049210. PMC 9661397. PMID 33092403.
  9. ^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.