Discovery of antitubulin agents with antiangiogenic activity as single entities with multitarget chemotherapy potential

ACS Medicinal Chemistry Letters

Volumn 5, Issue 5, 2014, Pages 480-484

  Gangjee, Aleem ^a   Pavana, Roheeth Kumar ^a   Ihnat, Michael A ^b   Thorpe, Jessica E ^b   Disch, Bryan C ^d   Bastian, Anja ^b   Bailey Downs, Lora C ^b   Hamel, Ernest ^c   Bai, Rouli ^c  

^a DUQUESNE UNIVERSITY   (United States)

^b UNIVERSITY OF OKLAHOMA COLLEGE OF PHARMACY   (United States)

^c FREDERICK NATIONAL LABORATORY FOR CANCER RESEARCH   (United States)

^d NONE

Author keywords

antiangiogenic; antimitotic; Antitubulin; combination chemotherapy; VEGFR2 inhibition

Indexed keywords

ANGIOGENESIS INHIBITOR; ANTIMITOTIC AGENT; ANTITUBULIN AGENT; BETA TUBULIN; CASPASE 3; COMBRETASTATIN A4; DOCETAXEL; MULTIDRUG RESISTANCE PROTEIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PACLITAXEL; SUNITINIB; TEMOZOLOMIDE; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 2 INHIBITOR;

ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BASAL LIKE BREAST CANCER; BINDING SITE; BREAST CANCER CELL LINE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CHORIOALLANTOIS; CONTROLLED STUDY; CYTOTOXICITY; DNA CONTENT; DRUG DESIGN; DRUG EFFICACY; DRUG SYNTHESIS; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE; LUNG METASTASIS; MICROTUBULE; MICROTUBULE ASSEMBLY; MOUSE; NONHUMAN; ONCOLOGICAL PARAMETERS; OVARIAN CANCER CELL LINE; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; TRIPLE NEGATIVE BREAST CANCER; TUMOR CELL; TUMOR CELL LINE; TUMOR GROWTH; TUMOR RESISTANCE; TUMOR VASCULAR DENSITY; WESTERN BLOTTING; WILD TYPE;

EID: 84900445558     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml4004793     Document Type: Article

References (16)

1. Young, R. J.; Reed, M. W. Anti-angiogenic therapy: Concept to clinic Microcirculation 2012, 19, 115-25
2. Shibuya, M. Vascular endothelial growth factor and its receptor system: Physiological functions in angiogenesis and pathological roles in various diseases J. Biochem. 2013, 153, 13-19
3. Bergers, G.; Hanahan, D. Modes of resistance to anti-angiogenic therapy Nat. Rev. Cancer 2008, 8, 592-603
4. Jain, R. K. Normalizing tumor microenvironment to treat cancer: Bench to bedside to biomarkers J. Clin. Oncol. 2013, 31, 2205-2218
5. Gangjee, A.; Zaware, N.; Raghavan, S.; Ihnat, M.; Shenoy, S.; Kisliuk, R. L. Single agents with designed combination chemotherapy potential: Synthesis and evaluation of substituted pyrimido[4,5- b ]indoles as receptor tyrosine kinase and thymidylate synthase inhibitors and as antitumor agents J. Med. Chem. 2010, 53, 1563-1578
6. Gangjee, A.; Zhao, Y.; Ihnat, M. A.; Thorpe, J. E.; Bailey-Downs, L. C.; Kisliuk, R. L. Novel tricyclic indeno[2,1- d ]pyrimidines with dual antiangiogenic and cytotoxic activities as potent antitumor agents Bioorg. Med. Chem. 2012, 20, 4217-4225
7. Gangjee, A.; Li, W.; Lin, L.; Zeng, Y.; Ihnat, M.; Warnke, L. A.; Green, D. W.; Cody, V.; Pace, J.; Queener, S. F. Design, synthesis, and X-ray crystal structures of 2,4-diaminofuro[2,3- d ]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors Bioorg. Med. Chem. 2009, 17, 7324-7336
8. Gangjee, A.; Zeng, Y.; Ihnat, M.; Warnke, L. A.; Green, D. W.; Kisliuk, R. L.; Lin, F.-T. Novel 5-substituted, 2,4-diaminofuro[2,3- d ]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors with antiangiogenic and antitumor activity Bioorg. Med. Chem. 2005, 13, 5475-5491
9. Dumontet, C.; Jordan, M. A. Microtubule-binding Agents: A dynamic field of cancer therapeutics Nat. Rev. Drug Discovery 2010, 9, 790-803
10. www.clinicaltrials.gov.
11. Gangjee, A.; Pavana, R. K.; Li, W.; Hamel, E.; Westbrook, C.; Mooberry, S. L. Novel water-soluble substituted pyrrolo[3,2- d ]pyrimidines: design, synthesis, and biological evaluation as antitubulin antitumor agents Pharm. Res. 2012, 29, 3033-3039
12. Gangjee, A.; Zaware, N.; Raghavan, S.; Yang, J.; Thorpe, J. E.; Ihnat, M. A. N(4)-(3-Bromophenyl)-7-(substituted benzyl) pyrrolo[2,3- d ]pyrimidines as potent multiple receptor tyrosine kinase inhibitors: design, synthesis, and in vivo evaluation Bioorg. Med. Chem. 2012, 20, 2444-2454
13. Ganguly, A.; Cabral, F. New insights into mechanisms of resistance to microtubule inhibitors Biochim. Biophys. Acta 2011, 1816, 164-171
14. Elliott, A. J.; Morris, P. E.; Petty, S. L.; Williams, C. H. An improved synthesis of 7-substituted pyrrolo[3,2- d ]pyrimidines J. Org. Chem. 1997, 62, 8071-8075
15. Luceome Biotechnologies, 1775 S. Pantano Rd, Suite 100, Tucson, AZ 85710.
16. Chambers, A. F. MDA-MB-435 and M14 cell lines: Identical but not M14 melanoma? Cancer Res. 2009, 69, 5292-5293