Small-molecule inhibitors targeting G-protein-coupled Rho guanine nucleotide exchange factors

Proceedings of the National Academy of Sciences of the United States of America

Volumn 110, Issue 8, 2013, Pages 3155-3160

  Shang, Xun ^a   Marchioni, Fillipo ^a   Evelyn, Chris R ^a   Sipes, Nisha ^a   Zhou, Xuan ^a   Seibel, William ^b   Wortman, Matthew ^b   Zheng, Yi ^a  

^a CINCINNATI CHILDREN S HOSPITAL RESEARCH FOUNDATION   (United States)

^b UNIVERSITY OF CINCINNATI   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

G PROTEIN COUPLED RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; GUANINE NUCLEOTIDE EXCHANGE FACTOR; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; RHO KINASE; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; UNCLASSIFIED DRUG; Y16 PROTEIN;

ARTICLE; BINDING AFFINITY; BREAST CANCER; CANCER CELL; CANCER GROWTH; CANCER INHIBITION; CELL ACTIVITY; CELL FUNCTION; CELL INVASION; CELL STRAIN MCF 7; HUMAN; PRIORITY JOURNAL; PROTEIN BINDING;

AMINO ACID SEQUENCE; CELL DIVISION; CELL LINE, TUMOR; CELL MOVEMENT; GUANINE NUCLEOTIDE EXCHANGE FACTORS; HUMANS; NEOPLASM INVASIVENESS; SEQUENCE HOMOLOGY, AMINO ACID;

EID: 84874269976     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1212324110     Document Type: Article

References (27)

1. Etienne-Manneville S, Hall A (2002) Rho GTPases in cell biology. Nature 420 (6916):629-635.
2. Ridley AJ (2001) Rho family proteins: Coordinating cell responses. Trends Cell Biol 11 (12):471-477.
3. Zohn IM, Campbell SL, Khosravi-Far R, Rossman KL, Der CJ (1998) Rho family proteins and Ras transformation: The RHOad less traveled gets congested. Oncogene 17 (11 Reviews):1415-1438.
4. Jaffe AB, Hall A (2005) Rho GTPases: Biochemistry and biology. Annu Rev Cell Dev Biol 21:247-269.
5. Rossman KL, Der CJ, Sondek J (2005) GEF means go: Turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol 6 (2):167-180.
6. Vigil D, Cherfils J, Rossman KL, Der CJ (2010) Ras superfamily GEFs and GAPs: Validated and tractable targets for cancer therapy? Nat Rev Cancer 10 (12):842-857.
7. Zheng Y (2001) Dbl family guanine nucleotide exchange factors. Trends Biochem Sci 26 (12):724-732.
8. Hart MJ, Eva A, Evans T, Aaronson SA, Cerione RA (1991) Catalysis of guanine nu-cleotide exchange on the CDC42Hs protein by the dbl oncogene product. Nature 354 (6351):311-314.
9. Cerione RA, Zheng Y (1996) The Dbl family of oncogenes. Curr Opin Cell Biol 8 (2):216-222.
10. Hart MJ, et al. (1994) Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product. J Biol Chem 269 (1):62-65.
11. Chikumi H, et al. (2004) Homo-and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C-terminal region regulates their in vivo Rho GEF activity and transforming potential. Oncogene 23 (1):233-240.
12. Hart MJ, et al. (1998) Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13. Science 280 (5372):2112-2114.
13. Fukuhara S, Murga C, Zohar M, Igishi T, Gutkind JS (1999) A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. J Biol Chem 274 (9):5868-5879.
14. Fukuhara S, Chikumi H, Gutkind JS (2001) RGS-containing RhoGEFs: The missing link between transforming G proteins and Rho? Oncogene 20 (13):1661-1668.
15. Fukuhara S, Chikumi H, Gutkind JS (2000) Leukemia-associated Rho guanine nucle-otide exchange factor (LARG) links heterotrimeric G proteins of the G (12) family to Rho. FEBS Lett 485 (2-3):183-188.
16. Lappano R, Maggiolini M (2011) G protein-coupled receptors: Novel targets for drug discovery in cancer. Nat Rev Drug Discov 10 (1):47-60.
17. Verdine GL, Walensky LD (2007) The challenge of drugging undruggable targets in cancer: Lessons learned from targeting BCL-2 family members. Clin Cancer Res 13 (24):7264-7270.
18. Hopkins AL, Groom CR (2002) The druggable genome. Nat Rev Drug Discov 1 (9):727-730.
19. Hopkins AL, Groom CR (2003) Target analysis: A priori assessment of druggability. Ernst Schering Res Found Workshop 42 (42):11-17.
20. Russ AP, Lampel S (2005) The druggable genome: An update. Drug Discov Today 10 (23-24):1607-1610.
21. Kristelly R, Gao G, Tesmer JJ (2004) Structural determinants of RhoA binding and nucleotide exchange in leukemia-associated Rho guanine-nucleotide exchange factor. J Biol Chem 279 (45):47352-47362.
22. Irwin JJ, Sterling T, Mysinger MM, Bolstad ES, Coleman RG (2012) ZINC: A free tool to discover chemistry for biology. J Chem Inf Model 2012 (Jun):15.
23. Krieger E, Darden T, Nabuurs SB, Finkelstein A, Vriend G (2004) Making optimal use of empirical energy functions: Force-field parameterization in crystal space. Proteins 57 (4):678-683.
24. Wienken CJ, Baaske P, Rothbauer U, Braun D, Duhr S (2010) Protein-binding assays in biological liquids using microscale thermophoresis. Nat Commun 1:100.
25. Shang X, et al. (2012) Rational design of small molecule inhibitors targeting RhoA subfamily Rho GTPases. Chem Biol 19 (6):699-710.
26. Dontu G, et al. (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17 (10):1253-1270.
27. Gao Y, Dickerson JB, Guo F, Zheng J, Zheng Y (2004) Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci USA 101 (20):7618-7623.