Ligand id: 8912

Name: acalabrutinib

Structure and Physico-chemical Properties

2D Structure
Click here for structure editor
Calculated Physico-chemical Properties
Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 118.51
Molecular weight 465.19
XLogP 4.09
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Having already received FDA Orphan Drug Designation and Breakthrough Therapy Designation for mantle cell lymphoma (MCL: a rare and fast-growing type of non-Hodgkin lymphoma), in August 2017 the FDA granted priority review for acalabrutinib's New Drug Application (NDA), based on results from a Phase 2 study in relapsed/refractory MCL (NCT02213926). This resulted in full FDA approval in October 2017 (link to FDA announcement). This approval is for the treatment of MCL patients who have received at least one prior therapy.

Additional trials are evaluating acalabrutinib in other cancers. For example: Phase 3 trial in patients with chronic lymphocytic leukemia (CLL)- see NCT02475681 and NCT02477696; Phase 2 clinical trials to assess acalabrutinib's efficacy against other B cell malignancies and a variety of solid tumours (such as bladder, prostate and non-small cell lung cancers). In total, more than 25 acalabrutinib clinical trials are underway or have completed. For a list of all registered trials, link here to Phase 1/2 trial results in patients with CLL are reported by Byrd et al. (2015) [2].

In the European Union, the EMA has granted acalabrutinib orphan designation for three rare diseases (as of 2016): chronic lymphocytic leukaemia / small lymphocytic lymphoma, lymphoplasmacytic lymphoma and mantle cell lymphoma.
Mechanism Of Action and Pharmacodynamic Effects
Under normal conditions BTK plays an important role in B lymphocyte development, activation, signaling, proliferation and survival, via activation of the B-cell antigen receptor (BCR) signaling pathway . BTK is known to be overexpressed in B-cell malignancies. Inhibition of BTK prevents the activation of B-cells and BTK-mediated activation of downstream survival pathways. This leads to inhibition of the growth of malignant B cells overexpressing BTK.