Search | VHL Regional Portal

ABSTRACT

Rearrangements of anaplastic lymphoma kinase (ALK) are associated with several cancer diseases. Due to resistance development against existing ALK-inhibitors, new, structurally unrelated inhibitors are required. By a scaffold hopping strategy, 6,8-disubstituted purines were designed as analogues of similar ALK-inhibiting thieno[3,2-d]pyrimidines. While the new title compounds indeed inhibited ALK and several ALK mutants in submicromolar concentrations, they retained poor water solubility.

Subject(s)

Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Purines/chemistry , Purines/pharmacology , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Anaplastic Lymphoma Kinase , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Binding Sites/drug effects , Binding Sites/physiology , Humans , Molecular Docking Simulation/methods , Protein Kinase Inhibitors/metabolism , Protein Structure, Tertiary , Purines/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Structure-Activity Relationship

ABSTRACT

Subject(s)

SEND TO:

SELECTION OF CITATIONS

SEARCH DETAIL