title: Lead optimization of HMBA to develop potent HEXIM1 inducers.
abstract: The potency of a series of Hexamethylene bis-acetamide (HMBA) derivatives inducing Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) was determined in LNCaP prostate cancer cells. Several compounds with unsymmetrical structures showed significantly improved activity. Distinct from HMBA, these analogs have increased hydrophobicity and can improve the short half-life of HMBA, which is one of the factors that have limited the application of HMBA in clinics. The unsymmetrical scaffolds of the new analogs provide the basis for further lead optimization of the compounds using combinatorial chemistry strategy.
authors: Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA.
authors: Bo
authors: B
authors: Zhong
authors: Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA.
authors: Rati
authors: R
authors: Lama
authors: Department of Pharmacology, Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106, USA.
authors: Wannarasmi
authors: W
authors: Ketchart
authors: Department of Pharmacology, Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106, USA. Electronic address: monica.montano@case.edu.
authors: Monica M
authors: MM
authors: Montano
authors: Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA; Center for Gene Regulation in Health and Disease, College of Sciences & Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA. Electronic address: B.su@csuohio.edu.
authors: Bin
authors: B
authors: Su
mesh_terms: D000081:Acetamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D015195:Drug Design; D005786:Gene Expression Regulation / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D000081:Acetamides; C476123:HEXIM1 protein, human; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C014026:hexamethylene bisacetamide
keywords: Derivatives; Drug development; HEXIM1; HMBA