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. Author manuscript; available in PMC: 2015 Oct 7.
Published in final edited form as: J Med Chem. 2015 Aug 11;58(16):6359–6367. doi: 10.1021/acs.jmedchem.5b00102

Table 3.

cAMP Assay Results of N-Methylated Ac-Nle4-c[Asp5,d-Nal(2′)7,Lys10]-NH2 Analogues at hMCRsa

hMC1R hMC3R hMC4R hMC5R
# sequence EC50, nM %max EC50, nM %max EC50, nM %max EC50, nM %max
1 Nle D H DNal(2′) R W K 14.8±2.0 96 >10000 NA >10000 NA 7 100
2 Nle D H DNal(2′) R W K 5.0±0.8 83 >10000 NA >10000 NA 60±5 100
3 Nle D H DNal(2′) R W K >10000 29 >10000 17 >10000 19 169±14 100
4 Nle D H DNal(2′) R W K 50.8±8 100 >10000 NA >10000 NA 1060±100 100
5 Nle D H DNal(2′) R W K 2210±310 100 >10000 NA >10000 NA >10000 NA
6 Nle D H DNal(2′) R W K 115±12 83 >10000 NA >10000 NA >10000 100
7 Nle D H DNal(2′) R W K 36±4 13 162±12 19 152±30 29 1560±210 100
8 Nle D H DNal(2′) R W K 2.1±0.8 100 >10000 NA* >10000 NA 446±50 100
9 Nle D H DNal(2′) R W K 563±70 9 709±87 22 2400±290 16 >1 0000 NA
10 Nle D H DNal(2′) R W K 315±40 100 >10000 NA >10000 NA >10000 NA
11 Nle D H DNal(2′) R W K 1560±170 64 463±52 18 >10000 19 460±61 100
12 Nle D H DNal(2′) R W K 1171±21 13 9.92±1 28 264±31 21 >2000 NA
13 Nle D H DNal(2′) R W K 1160±52 3 16±0.8 34 2100±231 31 >2000 NA
14 Nle D H DNal(2′) R W K 759 76 13.2±0.9 78 35.5±3.9 73 >10000 NA
15 Nle D H DNal(2′) R W K 3.7±0.6 96 >10000 NA* >10000 NA >10000 NA
16 Nle D H DNal(2′) R W K >10000 NA >10000 NA >10000 NA >10000 NA
17 Nle D H DNal(2′) R W K >10000 NA >10000 NA* 5±0.9 67 >10000 NA
18 Nle D H DNal(2′) R W K 214±35 100 >10000 NA 197±29 58 >10000 NA
19 Nle D H DNal(2′) R W K >3000 10* 11.±1 14* 9060±110 19* 1.1±0.1 30*
20 Nle D H DNal(2′) R W K >3000 22 1810±190 58 138±15 31 >3000 NA
21 Nle D H DNal(2′) R W K 23 36 2370±180 35 1570±170 52 239±20 100
22 Nle D H DNal(2′) R W K >1000 25 1790±213 34 946±78 28 >5000 NA
23 Nle D H DNal(2′) R W K 276±32 17 1.47±0.5 19 2190±178 45 >2000 NA
24 Nle D H DNal(2′) R W K 1970±213 60 802±91 21 1000±120 41 838±90 69
25 Nle D H DNal(2′) R W K 117±13 46 753±89 30 6590±912 18 62.5±9 40
26 Nle D H DNal(2′) R W K 366±41 32 1130±134 17 0.8±0.05 55 1680±192 26
27 Nle D H DNal(2′) R W K 841±91 35 3930±410 29 152±19 46 >10000 NA
28 Nle D H DNal(2′) R W K 26±3 85 326±41 34 67.6±9 20 0.8±0.1 100
29 Nle D H DNal(2′) R W K 58±11 52 5180±589 37 840±93 47 1450±14 NA
30 Nle D H DNal(2′) R W K 273±31 34 770±77 25 1110±141 51 818±83 NA
31 Nle D H DNal(2′) R W K 679±98 64 1950±200 41 485±67 55 1520±19 NA
32 Nle D H DNal(2′) R W K 25.7±7 23* 1400±150 26 1450±1 62 50 >1 0000 NA
a

Amino acids with N-methyl groups are highlighted in gray. EC50, effective concentration of peptide that was able to generate 50% maximal intracellular cAMP accumulation (N = 4). Percent activity, percent of cAMP produced at 10 µM ligand concentration in relation to Ac-Nle4-c[Asp5,d-Phe7,Lys10]-α-MSH(4–10)-NH2 (MT-II). NA, 0% cAMP accumulation observed at 10 µM. The peptides were tested at a range of concentrations from 10−10 to 10−5 M.

*

Asterisks show the lignds and receptors for which we have determined pA2 values. The pA2 values for the peptide 8, 15, and 17 at the hMC3R are 9.1, 8.2, and 8.5, respectively; The pA2 values for the peptide 19 at the hMC1R, hMC3R, hMC4R, hMC5R are 7.5, 8, 8, and 7.4, respectively. The pA2 value for peptide 32 at the hMC1R is 8.8.