Lex Van der Ploeg received his Ph.D. in enzymology and molecular genetics in 1984 from Amsterdam University. He subsequently joined the faculty of the department of Genetics and Development, College of Physicians and Surgeons at Columbia University where he received tenure in 1987. Dr. Van der Ploeg currently holds an adjunct faculty position in the department of Genetics and Development. Since joining Merck in 1991 as Director of the department of Genetics and Molecular Biology, he has carried diverse responsibilities which included the development of Merck’s obesity franchise, site head for MRL San Diego and now site head for MRL Boston.  Dr. Van der Ploeg has received numerous awards and grants for his research and has published over 200 research articles. He is an inventor on over 40 patents and patent applications.

His licensing and collaboration experiences include target and technology evaluation for the development of the obesity programs and the identification of late stage clinical leads for the treatment of neurodegenerative diseases and cancer.

Selected Key Publications, 2003 – Present
Grieco P, Balse-Srinivasan P, Han G, Weinberg D, MacNeil T, Van der Ploeg LH, Hruby VJ.
Extensive structure-activity studies of lactam derivatives of MT-II and SHU-9119: their activity and selectivity at human melanocortin receptors 3, 4, and 5. J Pept Res. 2003 Nov;62(5):199-206.

Sabatier N, Caquineau C, Dayanithi G, Bull P, Douglas AJ, Guan XM, Jiang M, Van der Ploeg L, Leng G.
Alpha-melanocyte-stimulating hormone stimulates oxytocin release from the dendrites of hypothalamic neurons while inhibiting oxytocin release from their terminals in the neurohypophysis. J Neurosci. 2003 Nov 12;23(32):10351-8.

Ujjainwalla F, Warner D, Walsh TF, Wyvratt MJ, Zhou C, Yang L, Kalyani RN, MacNeil T, Van der Ploeg LH, Rosenblum CI, Tang R, Vongs A, Weinberg DH, Goulet MT.
Design and syntheses of melanocortin subtype-4 receptor agonists: evolution of the pyridazinone archetype. Bioorg Med Chem Lett. 2003 Dec 15;13(24):4431-5.

Chen HY, Trumbauer ME, Chen AS, Weingarth DT, Adams JR, Frazier EG, Shen Z, Marsh DJ, Feighner SD, Guan XM, Ye Z, Nargund RP, Smith RG, Van der Ploeg LH, Howard AD, MacNeil DJ, Qian S.
Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology. 2004 Jun;145(6):2607-12.

Varnerin JP, Chung CC, Patel SB, Scapin G, Parmee ER, Morin NR, MacNeil DJ, Cully DF, Van der Ploeg LH, Tota MR.
Expression, refolding, and purification of recombinant human phosphodiesterase 3B: definition of the N-terminus of the catalytic core. Protein Expr Purif. 2004 Jun;35(2):225-36.

Scapin G, Patel SB, Chung C, Varnerin JP, Edmondson SD, Mastracchio A, Parmee ER, Singh SB, Becker JW, Van der Ploeg LH, Tota MR.
Crystal structure of human phosphodiesterase 3B: atomic basis for substrate and inhibitor specificity. Biochemistry. 2004 May 25;43(20):6091-100.

Palucki BL, Park MK, Nargund RP, Ye Z, Sebhat IK, Pollard PG, Kalyani RN, Tang R, Macneil T, Weinberg DH, Vongs A, Rosenblum CI, Doss GA, Miller RR, Stearns RA, Peng Q, Tamvakopoulos C, McGowan E, Martin WJ, Metzger JM, Shepherd CA, Strack AM, Macintyre DE, Van der Ploeg LH, Patchett AA.
Discovery of (2S)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-4-methyl-2-piperazinecarboxamide (MB243), a potent and selective melanocortin subtype-4 receptor agonist. Bioorg Med Chem Lett. 2005 Jan 3;15(1):171-5.

Meurer LC, Finke PE, Mills SG, Walsh TF, Toupence RB, Debenham JS, Goulet MT, Wang J, Tong X, Fong TM, Lao J, Schaeffer MT, Chen J, Shen CP, Sloan Stribling D, Shearman LP, Strack AM, Van der Ploeg LH.
Synthesis and SAR of 5,6-diarylpyridines as human CB1 inverse agonists. Bioorg Med Chem Lett. 2005 Feb 1;15(3):645-51.

Unmehopa UA, van Heerikhuize JJ, Spijkstra W, Woods JW, Howard AD, Zycband E, Feighner SD, Hreniuk DL, Palyha OC, Guan XM, Macneil DJ, Van der Ploeg LH, Swaab DF.
Increased melanin concentrating hormone receptor type I in the human hypothalamic infundibular nucleus in cachexia. J Clin Endocrinol Metab. 2005 Apr;90(4):2412-9.

Plummer CW, Finke PE, Mills SG, Wang J, Tong X, Doss GA, Fong TM, Lao JZ, Schaeffer MT, Chen J, Shen CP, Stribling DS, Shearman LP, Strack AM, Van der Ploeg LH.
Synthesis and activity of 4,5-diarylimidazoles as human CB1 receptor inverse agonists. Bioorg Med Chem Lett. 2005 Mar 1;15(5):1441-6.

Palucki BL, Park MK, Nargund RP, Tang R, MacNeil T, Weinberg DH, Vongs A, Rosenblum CI, Doss GA, Miller RR, Stearns RA, Peng Q, Tamvakopoulos C, Van der Ploeg LH, Patchett AA.
2-Piperazinecarboxamides as potent and selective melanocortin subtype-4 receptor agonists. Bioorg Med Chem Lett. 2005 Apr 15;15(8):1993-6.

Bakshi RK, Hong Q, Olson JT, Ye Z, Sebhat IK, Weinberg DH, MacNeil T, Kalyani RN, Tang R, Martin WJ, Strack A, McGowan E, Tamvakopoulos C, Miller RR, Stearns RA, Tang W, Maclntyre DE, van der Ploeg LH, Patchett AA, Nargund RP.
1-Amino-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid as a Tic mimetic: application in the synthesis of potent human melanocortin-4 receptor selective agonists. Bioorg Med Chem Lett. 2005 Jul 15;15(14):3430-3.

Ye Z, Guo L, Barakat KJ, Pollard PG, Palucki BL, Sebhat IK, Bakshi RK, Tang R, Kalyani RN, Vongs A, Chen AS, Chen HY, Rosenblum CI, MacNeil T, Weinberg DH, Peng Q, Tamvakopoulos C, Miller RR, Stearns RA, Cashen DE, Martin WJ, Metzger JM, Strack AM, MacIntyre DE, Van der Ploeg LH, Patchett AA, Wyvratt MJ, Nargund RP.
Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subtype-4 receptor agonist. Bioorg Med Chem Lett. 2005 Aug 1;15(15):3501-5.

Ujjainwalla F, Warner D, Snedden C, Grisson RD, Walsh TF, Wyvratt MJ, Kalyani RN, Macneil T, Tang R, Weinberg DH, Van der Ploeg L, Goulet MT.
Design and syntheses of melanocortin subtype-4 receptor agonists. Part 2: Discovery of the dihydropyridazinone motif. Bioorg Med Chem Lett. 2005 Jul 6.