Discovery of a potent, highly selective, and orally efficacious small-molecule activator of the insulin receptor

Journal of Medicinal Chemistry

Volumn 43, Issue 19, 2000, Pages 3487-3494

  Liu, K ^a   Xu, L ^a   Szalkowski, D ^a   Li, Z ^a   Ding, V ^a   Kwei, G ^a   Huskey, S ^a   Moller, D E ^a   Heck, J V ^a   Zhang, B B ^a   Jones, A B ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,5 DIHYDROXY 6 (1 METHYLINDOL 3 YL) 3 PHENYL 1,4 BENZOQUINONE; EPIDERMAL GROWTH FACTOR RECEPTOR; INSULIN RECEPTOR; PROTEIN TYROSINE KINASE; QUINONE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CALORIC RESTRICTION; DRUG EFFICACY; DRUG POTENCY; GLUCOSE BLOOD LEVEL; HYPERINSULINEMIA; INSULIN RESISTANCE; INSULIN RESPONSE; NON INSULIN DEPENDENT DIABETES MELLITUS; SIGNAL TRANSDUCTION;

ADMINISTRATION, ORAL; ANIMALS; BENZOQUINONES; CELL LINE; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION, PRECLINICAL; GLYBURIDE; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN; MACACA MULATTA; MALE; MICE; RATS; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, INSULIN; RECEPTORS, PLATELET-DERIVED GROWTH FACTOR; RECEPTORS, SOMATOMEDIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0034699358     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm000285q     Document Type: Article

References (45)

1. Structure and function of insulin receptors
2. After insulin binds
3. The human insulin receptor cDNA: The structural basis for hormane-activated transmenbrane signaling
4. Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes
5. Crystal structure of the tyrosine kinase domain of the human insulin receptor
6. Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analogue
7. The protein tyrosine kinase activity of the insulin receptor is necessary for insulin-mediated receptor downregulation
8. Pathogenesis of NIDDM
9. Role of insulin resistance in human disease
10. Oral agents and insulin in the treatment of non-insulin dependent diabetes mellitus
11. Charaterization of new oral antidiabetic agent CS-045
12. Novel thiazolidine-2,4-diones as potent euglycemic agents
13. The synthesis of BRL-49653 - A novel and potent antihyperglycemic agent
14. The glitazone family of antidiabetic agents
15. Novel antidiabetic and hypolipidemic agents. 3. Benzofuran-containing thiazolidinediones
16. MCC-555: A highly potent thiazolidinedione lacking hematological and cardiac side-effects
17. Hepatic dysfunction associated with troglitazone
18. Discovery of a small molecule insulin mimetic with antidiabetic activity in mice
19. Efficacy and pharmacokinetics of atovaquone and proguanil in children with multidrug-resistant plasmodium falciparum malaria
20. Phase I safety and pharmacokinetics study of micronized atovaquone in human immunodeficiency virus-infected infants and children
21. Randomised placebo-controlled study of atovaquone plus proguanil for malaria prophylaxis in children
22. Total synthesis of asterriquinone B1
23. The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptor
24. Efficacy of a hydroxynaphthoquinone 566C80 in experimental pneumocystis carinii pneumonitis
25. Examination of some factors responsible for a food-induced increase in absorption of atovaquone
26. Single-dose and steady-state pharmacokinetics of a novel microfluidized suspension of atovaquone in human immunodeficiency virus-seropositive patients
27. Population pharmacokinetics of atovaquone in patients with acute malaria caysed by plasmodium falciparum
28. Molecular mechanism of quinone cytotoxicity
29. Redox cycling and sulphydryl arylation: Their relative importance in the mechanism of quinone cytotoxicity to isolated hepatocytes
30. The addition and substitution chemistry of quinones
31. Studies on quinone thioesters. I. Mechanism of formation and properties of menadione
32. Interaction of menadione with glutathione
33. Mechanisms of toxicity of naphthoquinones to isolated hepatocytes
34. The role of oxidative processes in the cytotoxicity of substituted 1,4-naphthoquinones in isolated hepatocytes
35. Metabolism and reactions of quinoid anti-cancer agents
36. Atovaquone - A novel broad-spectrum anti-infective drug
37. The mechanism of uncoupling of oxidative phosphorylation by 2-methyl-1,4-naphthoquinone
38. Mutagenicity of quinones: Pathways of metabolic activation and detoxification
39. Haemolytic activity and nephrotoxicity of 2-hydroxy-1,4-naphthoquinone in rats