Ibrutinib

Ibrutinib
Clinical data
Trade names	Imbruvica, others
Other names	PCI-32765, CRA-032765
AHFS/Drugs.com	Monograph
MedlinePlus	a614007
License data	US DailyMed: Ibrutinib;
Pregnancy; category	AU: D; ;
Routes of; administration	By mouth
ATC code	L01EL01 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only; EU: Rx-only; In general: ℞ (Prescription only);
Pharmacokinetic data
Protein binding	97.3%
Metabolism	Hepatic (CYP3A & CYP2D6)
Elimination half-life	4–6 hours
Excretion	Feces (80%), urine (10%)
Identifiers
	IUPAC name 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	936563-96-1;
PubChem CID	24821094;
IUPHAR/BPS	6912;
DrugBank	DB09053;
ChemSpider	26637187;
UNII	1X70OSD4VX;
KEGG	D10223;
ChEBI	CHEBI:76612;
ChEMBL	ChEMBL1873475;
PDB ligand	1E8 (PDBe, RCSB PDB);
CompTox Dashboard (EPA)	DTXSID60893450 ;
ECHA InfoCard	100.232.543
Chemical and physical data
Formula	C25H24N6O2
Molar mass	440.507 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES 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 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]

^ "Ibrutinib (Imbruvica) Use During Pregnancy". Drugs.com. 3 December 2019. Retrieved 28 March 2020.
^ "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
^ "Regulatory Decision Summary for Imbruvica". Drug and Health Products Portal. 4 August 2023. Retrieved 2 April 2024.
^ "Imbruvica 140 mg Film-Coated Tablets - Summary of Product Characteristics (SmPC)". (emc). 16 January 2020. Retrieved 28 March 2020.
^ Cite error: The named reference UKlabel2016 was invoked but never defined (see the help page).
^ ^a ^b Cite error: The named reference Imbruvica FDA label was invoked but never defined (see the help page).
^ ^a ^b "Imbruvica EPAR". European Medicines Agency (EMA). 8 July 2021. Retrieved 14 July 2021.
^ 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.
^ 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.

[Drugs.com_pregnancy-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.

[UKlabel2016-5] Cite error: The named reference UKlabel2016 was invoked but never defined (see the help page).

[Imbruvica_FDA_label-6] Cite error: The named reference Imbruvica FDA label was invoked but never defined (see the help page).

[Imbruvica_EPAR-7] "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.

[WHO22nd-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.

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