Table 1.

The in vitro potency of CovX-Bodies tethered at different residues, indicated by K(0P), in blocking Ang2–Tie2 interaction and their mouse pharmacokinetics

Compound#SequenceIC50, nmol/LT1/2, h
Peptide 1QK(Ac)YQPLDELDK(Ac)TLYDQFMLQQG980.1
1K(0P)K(Ac)YQPLDELDK(Ac)TLYDQFMLQQG1.824
2QK(0P)YQPLDELDK(Ac)TLYDQFMLQQG0.313
3QK(Ac)K(0P)QPLDELDK(Ac)TLYDQFMLQQG0.218
4QK(Ac)YK(0P)PLDELDK(Ac)TLYDQFMLQQG>1,000ND
5QK(Ac)YQK(0P)LDELDK(Ac)TLYDQFMLQQG44.2ND
6QK(Ac)YQPK(0P)DELDK(Ac)TLYDQFMLQQG>1,000ND
7QK(Ac)YQPLK(0P)ELDK(Ac)TLYDQFMLQQG>1,000ND
8QK(Ac)YQPLDK(0P)LDK(Ac)TLYDQFMLQQG0.335
9QK(Ac)YQPLDEK(0P)DK(Ac)TLYDQFMLQQG2.072
10QK(Ac)YQPLDELK(0P)K(Ac)TLYDQFMLQQG>1,000ND
CVX-32QK(Ac)YQPLDELDK(0P)TLYDQFMLQQG0.374
12QK(Ac)YQPLDELDK(Ac)K(0P)LYDQFMLQQG0.156
13QK(Ac)YQPLDELDK(Ac)TK(0P)YDQFMLQQG>1,000ND
14QK(Ac)YQPLDELDK(Ac)TLK(0P)DQFMLQQG32.8ND
15QK(Ac)YQPLDELDK(Ac)TLYK(0P)QFMLQQG0.266
16QK(Ac)YQPLDELDK(Ac)TLYDK(0P)FMLQQG0.394
17QK(Ac)YQPLDELDK(Ac)TLYDQK(0P)MLQQG19.5ND
18QK(Ac)YQPLDELDK(Ac)TLYDQFK(0P)LQQG0.672
19QK(Ac)YQPLDELDK(Ac)TLYDQFMK(0P)QQG0.165
20QK(Ac)YQPLDELDK(Ac)TLYDQFMLK(0P)QG0.135
21QK(Ac)YQPLDELDK(Ac)TLYDQFMLQK(0P)G0.327
22QK(Ac)YQPLDELDK(Ac)TLYDQFMLQQK(0P)0.220
CVX-060QK(Ac)YQPLDEK(Ac)DK(0P)TLYDQFMLQQG0.5110
CVX-060TQK(Ac)YQPLDEK(Ac)DK(0P)TLYDQFMLQQG342ND
CVX-87QK(Ac)YQPLDELDK(0P)TLFDQFMLQQG0.261
Peptide 2TNFMPMDDLEQRLYEQFILQQG5.4ND
CVX-37(DFB)TNFMPMDDLEK(0P)RLYEQFILQQG0.426
CVX-51(0P)TNFMPMDDLEQRLYEQFILQQG1.828

NOTE: Compounds 1–10, 12–22, CVX-32, CVX-060, CVX-87, CVX-37, and CVX-51 were all tested as CovX-Bodies, while peptides 1, 2, and CVX-060T (the pharmacophores of CVX-060) were also tested as controls. The IC50s were average data from at least 3 independent preparations for each compound.

Abbreviations: ND, not determined; 0P, no PEG unit between peptide and the AZD linker; K(Ac), acetylated lysine; DFB, 1,5-difluorobenzoyl.