Table 1.
Affinity of human BnR subtypes for various agonist/antagonists.
| Affinity (nM) |
|||
|---|---|---|---|
| Variable | hNMBR (BB1) |
hGRPR (BB2) |
hBRS-3 (BB3) |
| I. Natural occurring Agonista | |||
| GRP | 148 | 0.19 | >3,000 |
| NMB | 0.052 | 35 | >3,000 |
| NMC [GRP(18–27)] | 37 | 0.14 | >3,000 |
| Bombesin (Bn) | 2 | 0.07 | >3,000 |
| II. Synthetic Agonistsa | |||
| [D-Phe6, β-Ala11, Phe13, Nle14] Bn 6–14 | 0.21 | 0.048 | 1.3 |
| [D-Phe6] Bn 6–14 | 1.3 | 0.17 | >3,000 |
| [D-Tyr6, (R)-Apa11, Phe13, Nle14] Bn 6–14b | 160 | 110 | 8.2 |
| [D-Tyr6, Apa-4Cl11, Phe13, Nle14] Bn 6–14b | 590 | 258 | 2.8 |
| Ac-Phe,Trp, Ala, His,(tBzl),Nip,Gly,Arg-NH2b | >10,000 | >10,000 | 63 |
| MK-5046 c | >10,000 | >10,000 | 18 |
| Compound 9G d | >10,000 | >10,000 | 70 |
| Compound 9D d | >10,000 | >10,000 | 121 |
| II. Antagonistsd | |||
| [D-Phe6] Bn 6–13 methyl ester | >10,000 | 4 | 5300 |
| [d-Tpi6, Leu13, Leu14, ψ13–14]Bn6–14 [RC3095] | 870 | 1 | >10,000 |
| PD 168368 | 0.51 | 1700 | >10,000 |
| PD 176252 | 0.53 | 170 | >3,000 |
| d-Nal, Cys,Tyr,d-Trp,Lys,Val,Cys,Nal-NH2 | 2500 | 605 | 340 |
| [[Tyr4, D-Phe12] Bn 6–14 | 3100 | 912 | >10,000 |
| [Leu13, ψ13–14, Leu14]Bn6–14 | >10,000 | 8 | >10,000 |
| [D-Phe6, Leu13,Cpa14, ψ/13-14]Bn6–14 | >10,000 | 1 | >10,000 |
| (3Ph-Pr6),His7, D -Ala11, D -Pro12, ψ13–14, Phe14]Bn(6–14)(BW2258U89) | 5,000 | 0.23 | 7,000 |
| [D-Arg1, D-Trp7,9, Leu11]substance P | >4,500 | 1,800 | >10,000 |
| Bantag-1 b | >10,000 | >10,000 | 1 |
Data are from [234]
Data are from [281]
Abbreviations : Ac, acetyl; Apa, 3-amino,propionic acid; Apa-4Cl, 4-chloro,3-amino,propionic acid; Bantag-1, Boc-Phe-His-4-amino-5-cyclohexyl-2,4,5-trideoxypentonyl-Leu-(3-dimethylamino) benzylamide N-methylammonium trifluoroacetate; Cpa, chlorophenylalamine, GRP, gastrin-releasing peptide; His(tBzl), histidine(tBenzl); MK-5046, (2S)-1,1,1-trifluoro-2-[4-(1H–pyrazol-1-yl)phenyl]-3-(4-[[1-(trifluoromethyl)cyclopropyl] methyl]-1H–imidazol-2-yl)propan-2-ol; Nip, piperidine-3 carboxylic acid; Nal, β-napthylalanine; Orn, ornithine; ψ; pseudopeptide bond, (i.e., CONH changed to CH2NH); Ph-Pr, phenylpropanolamine ; PD176252, (3-(1H–Indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[3-(4-nitro-phenyl)-ureido]-propionamide); PD168368, (3-(1H–Indol-3-yl)-2-methyl-2-[3(4-nitro-phenyl)-ureido]-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide; SP, substance P; Tpi,2.3.4.9-tetrahydro-1H–pyrido[3,4-b]indol-3carboxylic acid); (9g), [(5R)-4-([3-(2-methylpropoxy)phenyl]acetyl)-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H–pyrido[2,3-e][1,4]diazepin-5-yl]acetic acid [207]: 9D [207].