title: Kinase-mediated trapping of bi-functional conjugates of paclitaxel or vinblastine with thymidine in cancer cells.
abstract: In the present work, we explore the possibility of introducing selectivity to existing chemotherapeutics via the design of non-pro-drug, bi-functional molecules comprising a microtubule-binding agent and a substrate for a disease-associated kinase. The design, synthesis, and in vitro biological evaluation of paclitaxel-thymidine and vinblastine-thymidine bi-functional conjugates are reported here. This work provides the first account of 'kinase-mediated trapping' of cancer therapeutics.
authors.affiliation: Acidophil LLC, 2330 W. Joppa Road, Suite 330, Lutherville, MD 21093, USA. saspland@acidophil.com
authors.forename: Simon E
authors.initials: SE
authors.lastname: Aspland
authors.forename: Carlo
authors.initials: C
authors.lastname: Ballatore
authors.forename: Rosario
authors.initials: R
authors.lastname: Castillo
authors.forename: Joel
authors.initials: J
authors.lastname: Desharnais
authors.forename: Trisha
authors.initials: T
authors.lastname: Eustaquio
authors.forename: Philip
authors.initials: P
authors.lastname: Goelet
authors.forename: Zijian
authors.initials: Z
authors.lastname: Guo
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Nelson
authors.forename: Chengzao
authors.initials: C
authors.lastname: Sun
authors.forename: Angelo J
authors.initials: AJ
authors.lastname: Castellino
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Newman
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage*; D011494:Protein Kinases / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013936:Thymidine / Q000008:administration & dosage*; D014747:Vinblastine / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D014747:Vinblastine; D011494:Protein Kinases; D017239:Paclitaxel; D013936:Thymidine