Peptide Information

General Information of This Peptide
Peptide ID
PEP00017
Peptide Name
Peptide 1131
Structure
Sequence
CKNTALTTC
Peptide Type
Cyclic
Receptor Name
Kita-kyushu lung cancer antigen 1 (CT83)
  Receptor Info 
PDC Transmembrane Types Cell-penetrating peptides (CPPs)
Formula
C40H70N12O15S3
Isosmiles
[H]N[C@H](CS)C(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@]([H])([C@@H](C)O)NC(=O)[C@@]([H])([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@]([H])([C@@H](C)O)NC(=O)[C@@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChI
InChI=1S/C40H70N12O15S3/c1-16(2)11-23-34(60)51-30(20(6)55)39(65)52-29(19(5)54)38(64)49-26(40(66)67)15-70-69-14-25(48-32(58)21(42)13-68)36(62)45-22(9-7-8-10-41)33(59)47-24(12-27(43)56)35(61)50-28(18(4)53)37(63)44-17(3)31(57)46-23/h16-26,28-30,53-55,68H,7-15,41-42H2,1-6H3,(H2,43,56)(H,44,63)(H,45,62)(H,46,57)(H,47,59)(H,48,58)(H,49,64)(H,50,61)(H,51,60)(H,52,65)(H,66,67)/t17-,18+,19+,20+,21+,22-,23-,24+,25-,26-,28-,29-,30+/m0/s1
InChIKey
FFRNBDGZFKDTON-OKBHEYPESA-N
Pharmaceutical Properties
Molecule Weight
1055.27
Polar area
455.02
Complexity
1054.424573
xlogp Value
-6.7009
Heavy Count
70
Rot Bonds
16
Hbond acc
19
Hbond Donor
17
The Activity Data of This Peptide
Peptide Activity Information 1 [1]
Fluorescence intensity 2000
Binding Affinity Assay
For the fluorescence-linked immunosorbent assay (FLISA), flat-bottom 96-well cell culture plates (Thermo Fisher Scientific, Waltham, MA, USA) were coated with 10 μg/mL KK-LC-1 protein solution at 4 °C overnight and then blocked with 1% BSA-PBS at room temperature for 1 h. The plates were washed with PBS containing 0.1% Tween 20 (0.1% PBST). Three-fold dilutions of FITC-labeled 1131-MMAE, 1131 peptide and the non-targeting control CG7C-MMAE were added and incubated at room temperature for 2 h. The plates were washed again and the fluorescence intensity was measured with a multimode microplate reader (Tecan, Mendov, Switzerland). The excitation wavelength was 485 nm and emission wavelength was 535 nm.

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Experimental Condition 10 μg/mL KK-LC-1 protein solution at 4 C overnight
Each Peptide-drug Conjugate Related to This Peptide
Full Information of The Activity Data of The PDC(s) Related to This Peptide
1131-MMAE [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Gastric cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
3.87 nM
Administration Time 72 h
Description
We next evaluated the in vitro cytotoxicity of 1131-MMAE. NUGC-4, MKN45 and HGC27 cells were drug-treated for 72 h and their viability was assessed. 1131-MMAE killed KK-LC-1 positive gastric cancer cells with high potency. The IC50 values of 1131-MMAE were 3.87 nM for NUGC-4 cells and 5.26 nM for MKN45 cells. However, although a very high concentration was used, 1131-MMAE could only moderately inhibit the viability of KK-LC-1 negative HGC27 cells. The IC50 value of 1131-MMAE for HGC27 cells was 100-200 times higher than that in NUGC-4 and MNK45 cells. Free MMAE exerted cytotoxicity irrespective of the KK-LC-1 expression status. The IC50 values of free MMAE were 10.97 nM for NUGC-4 cells, 10.70 nM for MKN45 cells and 7.18 nM for HGC27 cells. Naked 1131 peptide showed no cytotoxicity to all three cell lines. These results were consistent with the KK-LC-1-dependent endocytosis and confirmed the target-selective killing of 1131-MMAE.

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In Vitro Model Gastric signet ring cell adenocarcinoma NUGC-4 cell CVCL_3082
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Gastric cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
5.26 nM
Administration Time 72 h
Description
We next evaluated the in vitro cytotoxicity of 1131-MMAE. NUGC-4, MKN45 and HGC27 cells were drug-treated for 72 h and their viability was assessed. 1131-MMAE killed KK-LC-1 positive gastric cancer cells with high potency. The IC50 values of 1131-MMAE were 3.87 nM for NUGC-4 cells and 5.26 nM for MKN45 cells. However, although a very high concentration was used, 1131-MMAE could only moderately inhibit the viability of KK-LC-1 negative HGC27 cells. The IC50 value of 1131-MMAE for HGC27 cells was 100-200 times higher than that in NUGC-4 and MNK45 cells. Free MMAE exerted cytotoxicity irrespective of the KK-LC-1 expression status. The IC50 values of free MMAE were 10.97 nM for NUGC-4 cells, 10.70 nM for MKN45 cells and 7.18 nM for HGC27 cells. Naked 1131 peptide showed no cytotoxicity to all three cell lines. These results were consistent with the KK-LC-1-dependent endocytosis and confirmed the target-selective killing of 1131-MMAE.

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In Vitro Model Gastric adenocarcinoma MKN45 cell CVCL_0434
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Gastric cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
786 nM
Administration Time 72 h
Description
We next evaluated the in vitro cytotoxicity of 1131-MMAE. NUGC-4, MKN45 and HGC27 cells were drug-treated for 72 h and their viability was assessed. 1131-MMAE killed KK-LC-1 positive gastric cancer cells with high potency. The IC50 values of 1131-MMAE were 3.87 nM for NUGC-4 cells and 5.26 nM for MKN45 cells. However, although a very high concentration was used, 1131-MMAE could only moderately inhibit the viability of KK-LC-1 negative HGC27 cells. The IC50 value of 1131-MMAE for HGC27 cells was 100-200 times higher than that in NUGC-4 and MNK45 cells. Free MMAE exerted cytotoxicity irrespective of the KK-LC-1 expression status. The IC50 values of free MMAE were 10.97 nM for NUGC-4 cells, 10.70 nM for MKN45 cells and 7.18 nM for HGC27 cells. Naked 1131 peptide showed no cytotoxicity to all three cell lines. These results were consistent with the KK-LC-1-dependent endocytosis and confirmed the target-selective killing of 1131-MMAE.

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In Vitro Model Gastric carcinoma HGC-27 cell CVCL_1279
References
Ref 1 An auristatin-based peptide-drug conjugate targeting Kita-Kyushu lung cancer antigen 1 for precision chemoradiotherapy in gastric cancer. Eur J Med Chem. 2022 Nov 5;241:114617. doi: 10.1016/j.ejmech.2022.114617. Epub 2022 Jul 19.