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Retrospective and Prospective Human Intravenous and Oral Pharmacokinetic Projection of Dipeptidyl peptidase-IV Inhibitors Using Simple Allometric Principles - Case Studies of ABT-279, ABT-341, Alogliptin, Carmegliptin, Sitagliptin and Vildagliptin.
Gilibili RR, Bhamidipati RK, Mullangi R, Srinivas NR. Gilibili RR, et al. J Pharm Pharm Sci. 2015;18(3):434-48. doi: 10.18433/j3tk55. J Pharm Pharm Sci. 2015. PMID: 26517136 Free article.
PURPOSE: The purpose of this exercise was to explore the utility of allometric scaling approach for the prediction of intravenous and oral pharmacokinetics of six dipeptidy peptidase-IV (DPP-IV) inhibitors viz. ABT-279, ABT-341, alogliptin, carmegliptin, sitagliptin …
PURPOSE: The purpose of this exercise was to explore the utility of allometric scaling approach for the prediction of intravenous and oral p …
LC-MS/MS determination of 2-(4-((2-(2S,5R)-2-Cyano-5-ethynyl-1-pyrrolidinyl)-2-oxoethylamino)-4-methyl-1-piperidinyl)-4-pyridinecarboxylic acid (ABT-279) in dog plasma with high-throughput protein precipitation sample preparation.
Kim J, Flick J, Reimer MT, Rodila R, Wang PG, Zhang J, Ji QC, El-Shourbagy TA. Kim J, et al. Biomed Chromatogr. 2007 Nov;21(11):1118-26. doi: 10.1002/bmc.855. Biomed Chromatogr. 2007. PMID: 17590862
In order to support the development of ABT-279, multiple analytical methods for an accurate, precise and selective concentration determination of ABT-279 in different matrices were developed and validated in accordance with the US Food and Drug Adminis …
In order to support the development of ABT-279, multiple analytical methods for an accurate, precise and selective concentrati …
Medicinal chemistry approaches to the inhibition of dipeptidyl peptidase-4 for the treatment of type 2 diabetes.
Havale SH, Pal M. Havale SH, et al. Bioorg Med Chem. 2009 Mar 1;17(5):1783-802. doi: 10.1016/j.bmc.2009.01.061. Epub 2009 Jan 31. Bioorg Med Chem. 2009. PMID: 19217790 Review.
Intense research activities in this area have resulted in the launch of sitagliptin and vildagliptin (in Europe only) and the advancement of a few others into preregistration/phase 3, for example, saxagliptin, alogliptin and ABT-279. Achieving desired selectivity fo …
Intense research activities in this area have resulted in the launch of sitagliptin and vildagliptin (in Europe only) and the advancement of …
Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes.
Madar DJ, Kopecka H, Pireh D, Yong H, Pei Z, Li X, Wiedeman PE, Djuric SW, Von Geldern TW, Fickes MG, Bhagavatula L, McDermott T, Wittenberger S, Richards SJ, Longenecker KL, Stewart KD, Lubben TH, Ballaron SJ, Stashko MA, Long MA, Wells H, Zinker BA, Mika AK, Beno DW, Kempf-Grote AJ, Polakowski J, Segreti J, Reinhart GA, Fryer RM, Sham HL, Trevillyan JM. Madar DJ, et al. J Med Chem. 2006 Oct 19;49(21):6416-20. doi: 10.1021/jm060777o. J Med Chem. 2006. PMID: 17034148
Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.0 nM) and selective (Ki(DPP8) > 30 microM; Ki(DPP9) > 30 microM) clinical candidate, ABT-279, that is orally available, efficacious, and remarkably safe in preclinical safety studies....
Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.0 nM) and selective (Ki(DPP8) > 30 microM; Ki(DPP9) > 30 microM) c …
Developing multiple high-throughput GLP methods for an investigational drug candidate in various matrices within a 96-well plate.
Zhang J, Kim EJ, Ji QC, El-Shourbagy TA. Zhang J, et al. Rapid Commun Mass Spectrom. 2006;20(24):3755-60. doi: 10.1002/rcm.2799. Rapid Commun Mass Spectrom. 2006. PMID: 17120270
The methods developed with this strategy are accurate, precise, selective, robust and matrix-independent. As an example, ABT-279 was used to demonstrate the feasibility of this strategy....
The methods developed with this strategy are accurate, precise, selective, robust and matrix-independent. As an example, ABT-279 …