Discovery of novel forkhead box O1 inhibitors for treating type 2 diabetes: Improvement of fasting glycemia in diabetic db/db mice

Molecular Pharmacology

Volumn 78, Issue 5, 2010, Pages 961-970

  Nagashima, Takeyuki ^a   Shigematsu, Nobuharu ^a   Maruki, Riyo ^a   Urano, Yasuharu ^a   Tanaka, Hirotsugu ^a   Shimaya, Akiyoshi ^a   Shimokawa, Teruhiko ^a   Shibasaki, Masayuki ^a  

^a ASTELLAS PHARMA INC   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

5 AMINO 7 (CYCLOHEXYLAMINO) 1 ETHYL 6 FLUORO 4 OXO 1,4 DIHYDROQUINOLINE 3 CARBOXYLIC ACID; ANTIDIABETIC AGENT; AS 1842856; GLUCOE 6 PHOSPHATASE; GLUCOSE; PHOSPHATASE; PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP); TRANSCRIPTION FACTOR FKHR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; DRUG EFFECT; DRUG MECHANISM; DRUG SCREENING; DRUG STRUCTURE; ENZYME INHIBITION; GENE EXPRESSION; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLUCOSE METABOLISM; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION;

ANIMALS; CELL LINE, TUMOR; FASTING; FORKHEAD TRANSCRIPTION FACTORS; GLUCOSE; GLUCOSE-6-PHOSPHATASE; HUMANS; HYPERGLYCEMIA; HYPOGLYCEMIC AGENTS; MALE; MASS SPECTROMETRY; MICE; NERVE TISSUE PROTEINS; PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP); PYRUVIC ACID; QUINOLONES; RATS; RNA, MESSENGER; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSCRIPTIONAL ACTIVATION;

EID: 77958127193     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.110.065714     Document Type: Article

References (23)

1. Altomonte J, Cong L, Harbaran S, Richter A, Xu J, Meseck M, and Dong HH (2004) Foxo1 mediates insulin action on apoC-III and triglyceride metabolism. J Clin Invest 114:1493-1503. (Pubitemid 40385579)
2. Altomonte J, Richter A, Harbaran S, Suriawinata J, Nakae J, Thung SN, Meseck M, Accili D, and Dong H (2003) Inhibition of Foxo1 function is associated with improved fasting glycemia in diabetic mice. Am J Physiol Endocrinol Metab 285:E718-E728. (Pubitemid 37176422)
3. Annis DA, Nickbarg E, Yang X, Ziebell MR, and Whitehurst CE (2007) Affinity selection-mass spectrometry screening techniques for small molecule drug discovery. Curr Opin Chem Biol 11:518-526. (Pubitemid 47588997)
4. Arion WJ, Canfield WK, Ramos FC, Schindler PW, Burger HJ, Hemmerle H, Schubert G, Below P, and Herling AW (1997) Chlorogenic acid and hydroxynitrobenzaldehyde: new inhibitors of hepatic glucose 6-phosphatase. Arch Biochem Biophys 339:315-322. (Pubitemid 27199976)
5. Biddinger SB, Haas JT, Yu BB, Bezy O, Jing E, Zhang W, Unterman TG, Carey MC, and Kahn CR (2008) Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nat Med 14:778-782.
6. Boden G, Chen X, and Stein TP (2001) Gluconeogenesis in moderately and severely hyperglycemic patients with type 2 diabetes mellitus. Am J Physiol Endocrinol Metab 280:E23-E30.
7. Furuyama T, Nakazawa T, Nakano I, and Mori N (2000) Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues. Biochem J 349:629-634. (Pubitemid 30465799)
8. Ganjam GK, Dimova EY, Unterman TG, and Kietzmann T (2009) FoxO1 and HNF-4 are involved in regulation of hepatic glucokinase gene expression by resveratrol. J Biol Chem 284:30783-30797.
9. Guo S, Rena G, Cichy S, He X, Cohen P, and Unterman T (1999) Phosphorylation of serine 256 by protein kinase B disrupts transactivation by FKHR and mediates effects of insulin on insulin-like growth factor-binding protein-1 promoter activity through a conserved insulin response sequence. J Biol Chem 274:17184-17192.
10. Hall RK, Yamasaki T, Kucera T, Waltner-Law M, O'Brien R, and Granner DK (2000) Regulation of phosphoenolpyruvate carboxykinase and insulin-like growth factor-binding protein-1 gene expression by insulin. The role of winged helix/forkhead proteins. J Biol Chem 275:30169-30175.
11. Jackson JG, Kreisberg JI, Koterba AP, Yee D, and Brattain MG (2000) Phosphorylation and nuclear exclusion of the forkhead transcription factor FKHR after epidermal growth factor treatment in human breast cancer cells. Oncogene 19:4574-4581.
12. Matsumoto M, Pocai A, Rossetti L, Depinho RA, and Accili D (2007) Impaired regulation of hepatic glucose production in mice lacking the forkhead transcription factor Foxo1 in liver. Cell Metab 6:208-216. (Pubitemid 47336849)
13. Matsuzaki H, Daitoku H, Hatta M, Tanaka K, and Fukamizu A (2003) Insulin-induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation. Proc Natl Acad Sci USA 100:11285-11290. (Pubitemid 37205927)
14. Nakae J, Biggs WH, 3rd, Kitamura T, Cavenee WK, Wright CV, Arden KC, and Accili D (2002) Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat Genet 32:245-253.
15. Nakae J, Kitamura T, Silver DL, and Accili D (2001) The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. J Clin Invest 108:1359-1367. (Pubitemid 33107764)
16. Onuma H, Vander Kooi BT, Boustead JN, Oeser JK, and O'Brien RM (2006) Correlation between FOXO1a (FKHR) and FOXO3a (FKHRL1) binding and the inhibition of basal glucose-6-phosphatase catalytic subunit gene transcription by insulin. Mol Endocrinol 20:2831-2847. (Pubitemid 44833539)
17. Perriello G, Pampanelli S, Del Sindaco P, Lalli C, Ciofetta M, Volpi E, Santeusanio F, Brunetti P, and Bolli GB (1997) Evidence of increased systemic glucose production and gluconeogenesis in an early stage of NIDDM. Diabetes 46:1010-1016. (Pubitemid 27221002)
18. Qu S, Altomonte J, Perdomo G, He J, Fan Y, Kamagate A, Meseck M, and Dong HH (2006) Aberrant Forkhead box O1 function is associated with impaired hepatic metabolism. Endocrinology 147:5641-5652. (Pubitemid 44833481)
19. Samuel VT, Choi CS, Phillips TG, Romanelli AJ, Geisler JG, Bhanot S, McKay R, Monia B, Shutter JR, Lindberg RA, Shulman GI, and Veniant MM (2006) Targeting foxo1 in mice using antisense oligonucleotide improves hepatic and peripheral insulin action. Diabetes 55:2042-2050. (Pubitemid 44509978)
20. Su D, Coudriet GM, Hyun Kim D, Lu Y, Perdomo G, Qu S, Slusher S, Tse HM, Piganelli J, Giannoukakis N, Zhang J, and Henry Dong H (2009) FoxO1 links insulin resistance to proinflammatory cytokine IL-1beta production in macrophages. Diabetes 58:2624-2633.
21. Wajngot A, Chandramouli V, Schumann WC, Ekberg K, Jones PK, Efendic S, and Landau BR (2001) Quantitative contributions of gluconeogenesis to glucose production during fasting in type 2 diabetes mellitus. Metab Clin Exp 50:47-52. (Pubitemid 32058548)
22. Yamagata K, Daitoku H, Shimamoto Y, Matsuzaki H, Hirota K, Ishida J, and Fukamizu A (2004) Bile acids regulate gluconeogenic gene expression via small heterodimer partner-mediated repression of hepatocyte nuclear factor 4 and Foxo1. J Biol Chem 279:23158-23165. (Pubitemid 38685621)
23. Zhang X, Gan L, Pan H, Guo S, He X, Olson ST, Mesecar A, Adam S, and Unterman TG (2002) Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by multiple mechanisms. Direct and indirect effects on nuclear/cytoplasmic shuttling and DNA binding. J Biol Chem 277:45276-45284. (Pubitemid 36159133)