The discovery of MK-4256, a potent SSTR3 antagonist as a potential treatment of type 2 diabetes

The discovery of MK-4256, a potent SSTR3 antagonist as a potential treatment of type 2 diabetes. He, S., Ye, Z., Truong, Q., Shah, S., Du, W., Guo, L., Dobbelaar, P., Lai, Z., Liu, J., Jian, T., Qi, H., Bakshi, R., Hong, Q., Dellureficio, J., Pasternak, A., Feng, Z., Dejesus, R., Yang, L., Reibarkh, M., Bradley, S., Holmes, M., Ball, R., Ruck, R., Huffman, M., Wong, F., Samuel, K., Reddy, V., Mitelman, S., Tong, S., Chicchi, G., Tsao, K., Trusca, D., Wu, M., Shao, Q., Trujillo, M., Eiermann, G., Li, C., Zhang, B., Howard, A., Zhou, Y., Nargund, R., & Hagmann, W. ACS Medicinal Chemistry Letters, 3(6):484-489, 2012. cited By 4

Paper doi abstract bibtex

A structure-activity relationship study of the imidazolyl-β- tetrahydrocarboline series identified MK-4256 as a potent, selective SSTR3 antagonist, which demonstrated superior efficacy in a mouse oGTT model. MK-4256 reduced glucose excursion in a dose-dependent fashion with maximal efficacy achieved at doses as low as 0.03 mg/kg po. As compared with glipizide, MK-4256 showed a minimal hypoglycemia risk in mice. © 2012 American Chemical Society.

@article{ He2012484,
  author = {He, S.a  and Ye, Z.a  and Truong, Q.a  and Shah, S.a  and Du, W.a  and Guo, L.a  and Dobbelaar, P.H.a  and Lai, Z.a  and Liu, J.a  and Jian, T.a  and Qi, H.a  and Bakshi, R.K.a  and Hong, Q.a  and Dellureficio, J.a  and Pasternak, A.a  and Feng, Z.a  and Dejesus, R.a  and Yang, L.a  and Reibarkh, M.a  and Bradley, S.A.a  and Holmes, M.A.a  and Ball, R.G.a  and Ruck, R.T.b  and Huffman, M.A.b  and Wong, F.b  and Samuel, K.c  and Reddy, V.B.c  and Mitelman, S.c  and Tong, S.X.c  and Chicchi, G.G.d  and Tsao, K.-L.d  and Trusca, D.d  and Wu, M.d  and Shao, Q.d  and Trujillo, M.E.d  and Eiermann, G.J.d  and Li, C.d  and Zhang, B.B.d  and Howard, A.D.d  and Zhou, Y.-P.d  and Nargund, R.P.a  and Hagmann, W.K.a },
  title = {The discovery of MK-4256, a potent SSTR3 antagonist as a potential treatment of type 2 diabetes},
  journal = {ACS Medicinal Chemistry Letters},
  year = {2012},
  volume = {3},
  number = {6},
  pages = {484-489},
  doi = {10.1021/ml300063m},
  note = {cited By 4},
  url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84862294249&partnerID=40&md5=7e62d778cc2ff4dff2bb23afc6a21b30},
  affiliation = {Department of Medicinal Chemistry, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, NJ 07065, United States; Department of Process Research, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, NJ 07065, United States; Department of Drug Metabolism and Pharmacokinetics, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, NJ 07065, United States; Department of Diabetes Research, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, NJ 07065, United States},
  abstract = {A structure-activity relationship study of the imidazolyl-β- tetrahydrocarboline series identified MK-4256 as a potent, selective SSTR3 antagonist, which demonstrated superior efficacy in a mouse oGTT model. MK-4256 reduced glucose excursion in a dose-dependent fashion with maximal efficacy achieved at doses as low as 0.03 mg/kg po. As compared with glipizide, MK-4256 showed a minimal hypoglycemia risk in mice. © 2012 American Chemical Society.},
  author_keywords = {β-tetrahydrocarboline;  antagonist;  SSTR3;  type 2 diabetes},
  document_type = {Article},
  source = {Scopus}
}

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