Chemical Property of Ibrutinib
Chemical Property:
- Boiling Point:715.0±60.0 °C at 760 mmHg
- PKA:4.09±0.30(Predicted)
- Flash Point:386.2±32.9 °C
- PSA：99.16000
- Density:1.3±0.1 g/cm3
- LogP:4.73640
- Storage Temp.:-20°C
- Solubility.:Soluble in DMSO ( up to at least 25 mg/ml)
- Purity/Quality:
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99%, *data from raw suppliers
Ibrutinib *data from reagent suppliers
Safty Information:
- Pictogram(s):
- Hazard Codes:
- MSDS Files:
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SDS file from LookChem
Useful:
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Description
Ibrutinib (chemical name 1 [(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1Hpyrazolo [3,4-d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one) is a first-in-class,potent, orally administered covalently-binding inhibitor of BTK.
Ibrutinib is a potent inhibitor of BTK that binds covalently to Cys-481 in the active site of BTK, resulting in inhibition of kinase activity. Ibrutinib does have significant activity against 19 other kinases, including seven with a cognate cysteine residue. These include BLK, BMX, ITK, TEC, EGFR, ERBB2, and JAK3. In November 2013, the US FDA approved ibrutinib (also referred to as PCI-32765), for the treatment of patients with mantle cell lymphoma (MCL) who had received at least one prior therapy. Ibrutinib is the second oral agent approved for the treatment of MCL. It works by irreversibly inhibiting Bruton’s tyrosine kinase (Btk) leading to the inhibition of B-cell receptor signaling and resulting in the reduction of malignant B-cell proliferation and induction of cell death. Btk plays an important role in the differentiation, development, proliferation, and survival of B cells via activation of cell-cycle regulators and regulating the expression of pro- and antiapoptotic proteins. Aberrant Btk activity results in a variety of B-cell malignancies including MCL. Ibrutinib inhibits Btk by irreversibly binding to cysteine-481 in the active site thereby inhibiting phosphorylation of tyrosine-223 and affecting downstream B-cell signaling pathways. Ibrutinib is a potent inhibitor of Btk (IC50=0.5 nM) and is efficacious in canine models of B-cell lymphoma. At dose ranges of 2.5–20 mg/kg, there was full occupancy of Btk in peripheral blood and tumor tissue for 24 h. A synthetic route to ibrutinib that employs Suzuki coupling of 3-iodo-1Hpyrazolo[3,4-d]pyrimidin-4-amine with (4-phenoxyphenyl)boronic acid followed by Mitsunobu reaction with N-Boc-3-hydroxypiperidine as key steps has been reported.
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Uses
Ibrutinib is a highly selective Bruton’s tyrosine kinase (Btk) irreversible inhibitor.
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Clinical Use
Tyrosine kinase inhibitor:
Treatment of mantle cell lymphoma (MCL) and
chronic lymphocytic leukaemia (CLL)
Treatment of Waldenstr?m’s macroglobulinaemia
(WM)
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Drug interactions
Potentially hazardous interactions with other drugs
Anti-arrhythmics: concentration possibly increased
by amiodarone and dronedarone - avoid or reduce
dose of ibrutinib.
Antibacterials: concentration possibly increased
by ciprofloxacin, clarithromycin, erythromycin and
telithromycin - avoid or reduce dose of ibrutinib;
concentration reduced by rifampicin - avoid.
Antidepressants: concentration possibly reduced by
St John’s wort - avoid.
Antiepileptics: concentration possibly reduced by
carbamazepine, fosphenytoin, phenobarbital and
phenytoin - avoid.
Antifungals: concentration possibly increased
by fluconazole, itraconazole, ketoconazole and
voriconazole - avoid or reduce dose of ibrutinib.
Antipsychotics: avoid with clozapine, increased risk
of agranulocytosis.
Antivirals: concentration possibly increased by
atazanavir, darunavir, fosamprenavir, indinavir,
ritonavir and saquinavir - avoid or reduce dose of
ibrutinib.
Aprepitant: concentration possibly increased - avoid
or reduce dose of ibrutinib.
Calcium channel blockers: concentration possibly
increased by diltiazem or verapamil - avoid or reduce
dose of ibrutinib.
Cobicistat: concentration possibly increased, avoid or
reduce dose of ibrutinib.
Cytotoxics: concentration possibly increased by
crizotinib - avoid or reduce dose of ibrutinib;
concentration possibly increased by imatinib -
reduce dose of ibrutinib.
Grapefruit juice and Seville oranges: avoid.
