HER2 is overexpressed and mutated in various types of cancer thus becoming prone to chemotherapy drug resistance. The purpose of this study was to investigate the potential of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) as inhibitors of HER2 (wild type and mutant). Data for these three small molecules and HER2 protein were obtained from the PubChem and RCSB PDB databases. Analysis of pharmacokinetic, drug-likeness and toxicity of the compounds performed using SwissAdme and ProTox-II web server. Confirmation of HER2 overexpression in various cancer types performed using the UALCAN web portal. Specific docking using AutoDock Vina was performed to simulate the HER2-compound interaction. Curcumin, DMC and BDMC had drug-likeness properties based on five parameters and also had good bioavailability. HER2 was confirmed to be overexpressed in BLCA, BRCA, CESC, CHOL, ESCA, GBM, LIHC, LUAD, PAAD, SKCM, THCA, STAD and UCEC. The docking simulation showed that curcumin and BDMC bound to the ATP binding pocket of both wild-type and mutant HER2. Curcumin and BDMC also would constantly have a lower binding affinity value than ATP and produce many hydrogen bonds. Curcumin and BDMC are predicted to have high potential as alternative drugs for wild-type and mutant HER2 inhibitors.
|Number of pages||9|
|Journal||Biochemical and Cellular Archives|
|Publication status||Published - Oct 2021|
- non-communicable disease