Discovery of a small molecule insulin mimetic with antidiabetic activity in mice

Science

Volumn 284, Issue 5416, 1999, Pages 974-977

  Zhang, Bei ^a   Salituro, Gino ^a   Szalkowski, Deborah ^a   Li, Zhihua ^a   Zhang, Yan ^a   Royo, Inmaculada ^c   Vilella, Dolores ^c   Díez, Maria Teresa ^c   Pelaez, Fernando ^c   Ruby, Caroline ^a   Kendall, Richard L ^b   Mao, Xianzhi ^b   Griffin, Patrick ^b   Calaycay, Jimmy ^b   Zierath, Juleen R ^d   Heck, James V ^a   Smith, Roy G ^a,e   Moller, David E ^a  

^a Dept of Molecular Endocrinology ^*  (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

^c Medical affairs Merck sharp and Dohme ltd   (Spain)

^d KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^e BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDIABETIC AGENT; INSULIN; INSULIN DERIVATIVE; INSULIN RECEPTOR; L 738281; SOMATOMEDIN RECEPTOR; TYROSINE KINASE RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG ISOLATION; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; FUNGUS; GLUCOSE BLOOD LEVEL; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL;

ANIMALIA; FUNGI;

EID: 0033532347     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.284.5416.974     Document Type: Article

References (28)

1. O. M. Rosen, Diabetes 38, 1508 (1939).
2. Y. Ebina et al., Cell 40, 747 (1985).
3. A. Ullrich et al., Nature 313, 756 (1985).
4. S. R. Hubbard, L. Wei, L. Ellis, W. A. Hendrickson, ibid. 372, 746 (1994).
5. S. R. Hubbard, EMBO J. 16, 5572 (1997).
6. M. F. White and C. R. Kahn, in Insulin Resistance, D. E. Moller, Ed. (Wiley, Chichester, UK, 1994), pp. 9-24.
7. B. L. Seely and J. M. Olefsky, in (6), pp. 187-252
8. L. J. Goodyear et al., J. Clin. Invest. 95, 2195 (1995).
9. J. F. Caro et al., ibid. 79, 1330 (1987).
10. Y. Ebina et al., Proc. Natl. Acad Sci. U.S.A. 82, 8014 (1985).
11. 13C, and two-dimensional nuclear magnetic resonance data and high-resolution fast atom bombardment mass spectroscopy) were collected on the pure compound, which was identified as demethylasterriquinone B-1 (L-783,281).
12. B. Zhang et al., unpublished data.
13. G. Endemann, K, Yonezawa, R. A. Roth, J. Biol. Chem. 265, 396 (1990); R. Levy-Toledano, M. Taouis, D. H. Blaettler, P. Gorden, S. Taylor, ibid. 269, 31178 (1994).
14. G. Endemann, K, Yonezawa, R. A. Roth, J. Biol. Chem. 265, 396 (1990); R. Levy-Toledano, M. Taouis, D. H. Blaettler, P. Gorden, S. Taylor, ibid. 269, 31178 (1994).
15. T. F. Franke et al., Cell 81, 727 (1995).
16. B. B. Kahn, I. A. Simpson, S. W. Cushman, J. Clin. Invest. 82, 691 (1988).
17. P. A. Hansen, E. A. Gulve, J. O. Holloszy, J. Appl. Physiol. 76, 979 (1994).
18. B. Zhang and R. A. Roth, J. Biol. Chem. 267, 18320 (1992).
19. 983 to the COOH-terminal stop codon) was cloned as an in-frame glutathione S-transferase fusion (GST-IRK) into the baculovirus expression vector pBlueBac 4.0 (Invitrogen, San Diego), and the resulting plasmid was transfected into Sf21 insect cells with the Bac-N-Blue Transfection Kit (Invitrogen). Recombinant virus was prepared and protein expressed as described [R. Kendall and K. Thomas, Proc. Natl. Acad. Sci. U.S.A. 90, 10705 (1993)].
20. The trypsin digestion products were separated and visualized in 4 to 20% SDS-polyacrylamide gel stained with Coomassie blue. After electrotransfer onto a polyvinylidene difluoride membrane, the 30-kD protein was excised and subjected to automated Edman sequence analysis with a 477A sequenator (Applied Biosystems).
21. Y. Ebina et al., Proc. Natl. Acad Sci. U.S.A. 84, 704 (1987); C. K. Chou et al., J. Biol. Chem. 262, 1842 (1987); D. A. McClain et al., ibid., p. 14663.
22. Y. Ebina et al., Proc. Natl. Acad Sci. U.S.A. 84, 704 (1987); C. K. Chou et al., J. Biol. Chem. 262, 1842 (1987); D. A. McClain et al., ibid., p. 14663.
23. Y. Ebina et al., Proc. Natl. Acad Sci. U.S.A. 84, 704 (1987); C. K. Chou et al., J. Biol. Chem. 262, 1842 (1987); D. A. McClain et al., ibid., p. 14663.
24. J. Meyerovitch, Z. Farfel, J. Sack, Y. Shechter, J. Biol. Chem. 262, 6658 (1987).
25. J. M. Denu, D. L. Kohse, J. Vijalakshmi, M. A. Saper, J. E. Dixon, Proc. Natl. Acad. Sci. U.S.A. 93, 2493 (1996).
26. B. Zhang et al., J. Biol. Chem. 269, 25735 (1994).
27. H. Wallberg-Henriksson, N. Zetan, J. Henriksson, ibid. 262, 7665 (1987).
28. We thank G. Bills, R. Schwartz, and L. So for characterization of the L-783,281-producing organism; D. Zink for mass spectroscopy data on L-783,281; T. Doebber, M. Wu, and J. Ryder for assistance with biological characterization; and M. Turner and S. Gould for invaluable support.