Table 1.
Metabolically stable apelin analogs.
| Reference | Affinity (Ki, nM) | cAMP production inhibition (IC50, nM) | Half-life in plasmaa (min) | |
|---|---|---|---|---|
| Apelin-13 | ||||
| pE-R-P-R-L-S-H-K-G-P-M-P-F (pE13F) | (33) | 0.56 ± 0.07 | 1.68 ± 0.47 | 7.2 |
| E-R-P-R-L-S-H-K-G-P-Nle-P-2Nal | (48) | 1.2 ± 0.1 | 20.5 ± 6 | <120 |
| E-R-P-R-L-S-H-K-G-P-Nle-P-4Br(F) | (48) | 1.2 ± 0.1 | 12.4 ± 3 | <60 |
| E-R-P-R-L-S-H-K-G-P-Nle-Aib-F | (48) | 1.8 ± 0.2 | 20.9 ± 7 | <60 |
| pE-R-P-R-L-S-H-K-G-P-Nle-P-Bpa | (42, 53) | 0.38 ± 0.04 | 0.04 ± 0.02 | 55 |
| pE-R-P-R-L-S-H-K-G-P-Nle-P-Y(O)Bn | (42, 53) | 0.016 ± 0.002 | 0.35 ± 0.09 | 66 |
| pE-R-P-R-L-S-H-K-G-P-Nle-P-F(L-αCH3) | (42, 53) | 0.34 ± 0.02 | 0.07 ± 0.02 | >120 |
| Cyclo(1-6)C-R-P-R-L-C-H-K-G-P-M-P | (50) | 300 | 2.7 ± 0.8 | ND |
| Palmitoyl-E-R-P-R-L-S-H-K-G-P-Nle-Aib-F | (46) | ND | 21.6 ± 4.5 | 1,740 |
| Cyclo(7-11)pE-R-P-R-L-S-AllyG-K-G-P-AllyG-P-Y(O)Bn | (51) | 1.7 ± 0.25 | 35 ± 11 | ND |
| Ac-E-R-P-R-(D)L-S-Aib-K-(D)A-P-Nle-P-4Br(F) | (33) | 2.11 ± 0.40 | 2.22 ± 1.00 | 86 |
| pE-R-P-R-L-S-H-K-G-P-Nle-Aib-Br(F) | (15) | ND | ND | >60 |
| Apelin-17 | ||||
| K-F-R-R-Q-R-P-R-L-S-H-K-G-P-M-P-F (K17F) | (33) | 0.06 ± 0.01 | 0.30 ± 0.10 | 4.6 |
| Ac-K-F-(D)R-R-(D)Q-R-P-R-(D)L-S-Aib-K-(D)A-P-Nle-P-4Br(F) (P92) | (33) | 0.09 ± 0.02 | 0.56 ± 0.32 | 24 |
| CF3((CF2)7(CH2)2C(O)-K-F-R-R-Q-R-P-R-L-S-H-K-G-P-M-P-F (LIT01-196) | (33) | 0.08 ± 0.01 | 1.71 ± 0.28 | >1,440 |
| K-F-R-R-Q-R-P-R-L-S-H-K-G-P-Nle-Aib-Br(F) | (15) | ND | ND | 30 |
| Apelin-36 | ||||
| L-V-Q-P-R-G-S-R-N-G-P-G-P-W-Q-G-G-R-R-K-F-R-R-Q-R-P-R-L-S-H-K-G-P-M-P-F | (6, 7, 43) | 4.8 ± 0.24 | 0.52 | <5b |
| 40 kDa-PEG-Apelin-36 | (44) | 0.3 | 1.5 | ND |
| Apelin-36-[L28C(30 kDa-PEG)] | (45) | ND | 3,050 ± 2,100 | ND |
aEx vivo plasma half-life (unless otherwise specified).
bIn vivo plasma half-life.
ND, not determined; G, glycine; AllyG, allylglycine; P, proline; A, alanine; V, valine; L, leucine; I, isoleucine; M, methionine; C, cysteine; F, phenylalanine; Y, tyrosine; W, tryptophan; H, histidine; K, lysine; R, arginine; Q, glutamine; N, asparagine; E, glutamic acid; D, aspartic acid; S, serine; T, threonine; Aib, aminoisobutyric acid; Y(O)Bn, tyrosine(O)benryl; Bpa, benzoïlphenyl; Nle, norleucine; 2Nal, naphtalen-2-yl-propanoic acid; 4Br(F), 4-bromo-phenylalanine; PEG, polyethyleneglycol.
In bold and italic characters: native apelin peptides.
In bold characters: name of the analog as it is referred in the article.