Orelabrutinib

Description

Orelabrutinib is a small molecule inhibitor of Bruton's tyrosine kinase with potential antineoplastic activity.

Description

In December 2020, orelabrutinib was approved by the China National Medical Products Administration for treating patients with relapsed/refractory MCL, CLL, and SLL. This compound is also being evaluated for the treatment of multiple sclerosis. Orelabrutinib, which has a unique pyridylcarboxamide hinge binder, showed an IC50 value of 1.6 nM in the BTK enzymatic assay. When tested against a panel of 456 kinases at 1 μM, orelabrutinib only inhibited BTK (>90%), while ibrutinib also targeted several other kinases, including EGFR, TEC, and BMX. Orelabrutinib has a favorable half-life of 4 h in healthy volunteers.1,2 It is administered orally at a daily dose of 150 mg.

Uses

Orelabrutinib has been previously approved to treat  patients with relapsed or refractory (R/R) mantle cell lymphoma and R/R  chronic lymphocytic leukemia/small lymphocytic lymphoma.

brand name

Innobruka^TM

General Description

Class: non-receptor tyrosine kinase
Treatment: CLL, SLL, MCL
Elimination half-life = 4 h
Protein binding = not reported

Biological Activity

Orelabrutinib (ICP-022) is a potent, orally active and irreversible inhibitor of Bruton's tyrosine kinase (BTK).

Mechanism of action

Upon administration, orelabrutinib binds to and inhibits the activity of BTK. This prevents both the activation of the B-cell antigen receptor (BCR)  signaling pathway and BTK-mediated activation of downstream survival  pathways, inhibiting the growth of malignant B-cells that overexpress  BTK.

target