stattic and Neoplasms

Hypoxia is a common characteristic of many types of solid tumors and is associated with tumor propagation, malignant progression, and resistance to anti-cancer therapy. HIF-1 pathway is one of the survival pathways activated in tumor in response to hypoxia. In hypoxic condition, hypoxia-inducible factor-1α (HIF-1α) is stabilized and translocated into nucleus where it forms heterodimer with HIF-1β and regulates the expression of a plethora of genes involved in different processes, such as cell proliferation, differentiation, apoptosis, vascularization/angiogenesis, tumor invasion and metastasis. Recruitment of co-activator p300 or CBP to HIF-1α is critical to the transactivation activity of HIF-1 dimer, therefore, small molecules which can block the dimerization of HIF-1α and HIF-1β or inhibit the interaction between HIF-1α and p300 can function as inhibitors of HIF-1 and have the potential to be developed as novel therapies for the treatment of human cancers. In this review, recent progress of small molecular inhibitors of protein-protein interactions targeting HIF-1 is summarized, the mechanism of functions of these compounds and their potential usage as anti-cancer agents have also been discussed.

Topics: Cell Hypoxia; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Models, Molecular; Molecular Conformation; Neoplasms; Protein Binding; Small Molecule Libraries

Topics: Animals; Antineoplastic Agents; Clinical Trials as Topic; Drug Design; High-Throughput Screening Assays; Humans; Neoplasms; Peptides; Peptidomimetics; Psoriasis; Signal Transduction; STAT3 Transcription Factor; Stem Cells; Structure-Activity Relationship

Topics: Animals; Antineoplastic Agents; Apoptosis; Benzofurans; Cell Line, Tumor; Drug Design; Female; Humans; Mice, Inbred BALB C; Molecular Docking Simulation; Molecular Structure; Naphthoquinones; Neoplasms; Protein Binding; S Phase Cell Cycle Checkpoints; STAT3 Transcription Factor; Structure-Activity Relationship; Xenograft Model Antitumor Assays