defactinib

Ligand id: 7910

Name: defactinib

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 11
Hydrogen bond donors 3
Rotatable bonds 10
Topological polar surface area 150.48
Molecular weight 510.14
XLogP 2.22
No. Lipinski's rules broken 1

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Three Phase II clinical trials are underway, two for malignant pleural mesothelioma (NCT01870609 and NCT02004028), and NCT01951690 for KRAS mutant non-small cell lung cancer.
Mechanism Of Action and Pharmacodynamic Effects
The tyrosine kinase FAK is a key signal transducer for integrins and growth factors, that is upregulated in many tumor cell types and is involved in tumor cell invasion, migration and proliferation [4]. Autophosphorylation of FAK at Tyr397 mediates interation with downstream signalling molecules including ERK, JNK/MAPK and PI3K/Akt [5,7]. FAK inhibition is therefore likely to prevent the activation of these signal transduction pathways, thus inhibiting tumor cell migration, proliferation and survival [2]. In addition, FAK inhibition with defactinib has been reported to overcome YB-1 (YBX1; P67809)-mediated paclitaxel resistance in in vitro tumour cell models, via an Akt-dependent pathway [3].