Peptide Information

General Information of This Peptide
Peptide ID
PEP00029
Peptide Name
GnRH analogs 2
Structure
Sequence
EHWSYCLRP-NHEt
Peptide Type
Linear
Receptor Name
Gonadotropin-releasing hormone receptor (GNRHR)
  Receptor Info 
PDC Transmembrane Types Cell targeting peptides (CTPs)
Formula
C55H76N16O12S
Isosmiles
[H]N/C(N)=N/CCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CS)NC(=O)[C@H](Cc1ccc(O[H])cc1)NC(=O)[C@H](CO[H])NC(=O)[C@H](Cc1cn([H])c2ccccc12)NC(=O)[C@H](Cc1cn([H])cn1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N1CCC[C@H]1C(=O)NC
InChI
InChI=1S/C55H76N16O12S/c1-29(2)20-38(47(76)64-37(10-6-18-60-55(56)57)54(83)71-19-7-11-44(71)53(82)58-3)65-52(81)43(27-84)70-48(77)39(21-30-12-14-33(73)15-13-30)66-51(80)42(26-72)69-49(78)40(22-31-24-61-35-9-5-4-8-34(31)35)67-50(79)41(23-32-25-59-28-62-32)68-46(75)36-16-17-45(74)63-36/h4-5,8-9,12-15,24-25,28-29,36-44,61,72-73,84H,6-7,10-11,16-23,26-27H2,1-3H3,(H,58,82)(H,59,62)(H,63,74)(H,64,76)(H,65,81)(H,66,80)(H,67,79)(H,68,75)(H,69,78)(H,70,77)(H4,56,57,60)/t36-,37-,38-,39-,40-,41-,42-,43+,44-/m0/s1
InChIKey
MRMDZLKSEQFGPK-YSUREIBVSA-N
Pharmaceutical Properties
Molecule Weight
1185.38
Polar area
431.54
Complexity
1184.554933
xlogp Value
-2.9445
Heavy Count
84
Rot Bonds
32
Hbond acc
15
Hbond Donor
16
The Activity Data of This Peptide
Peptide Activity Information 1 [1]
Cell viability 30%
Binding Affinity Assay
The antiproliferative effects of Dox and GnRH-Dox conjugates were determined in MCF-7 cells using the MTT assay.The results of antiproliferative activity of the three conjugates demonstrated that [d-Cys6-des-Gly10-Pro9-NHEt]-GnRH might have higher binding affinity to GnRH receptors than that of [d-Cys6, desGly10, Pro9-NH2]-GnRH and [d-Cys6, a-aza-Gly10-NH2]-GnRH.

   Click to Show/Hide
Experimental Condition MCF-7 cell; 100 μM
Peptide Activity Information 2 [1]
Cell viability 39%
Binding Affinity Assay
The antiproliferative effects of Dox and GnRH-Dox conjugates were determined in MCF-7 cells using the MTT assay.The results of antiproliferative activity of the three conjugates demonstrated that [d-Cys6-des-Gly10-Pro9-NHEt]-GnRH might have higher binding affinity to GnRH receptors than that of [d-Cys6, desGly10, Pro9-NH2]-GnRH and [d-Cys6, a-aza-Gly10-NH2]-GnRH.

   Click to Show/Hide
Experimental Condition MCF-7 cell; 75 μM
Peptide Activity Information 3 [1]
Cell viability 50%
Binding Affinity Assay
The antiproliferative effects of Dox and GnRH-Dox conjugates were determined in MCF-7 cells using the MTT assay.The results of antiproliferative activity of the three conjugates demonstrated that [d-Cys6-des-Gly10-Pro9-NHEt]-GnRH might have higher binding affinity to GnRH receptors than that of [d-Cys6, desGly10, Pro9-NH2]-GnRH and [d-Cys6, a-aza-Gly10-NH2]-GnRH.

   Click to Show/Hide
Experimental Condition MCF-7 cell; 50 μM
Peptide Activity Information 4 [1]
Cell viability 59%
Binding Affinity Assay
The antiproliferative effects of Dox and GnRH-Dox conjugates were determined in MCF-7 cells using the MTT assay.The results of antiproliferative activity of the three conjugates demonstrated that [d-Cys6-des-Gly10-Pro9-NHEt]-GnRH might have higher binding affinity to GnRH receptors than that of [d-Cys6, desGly10, Pro9-NH2]-GnRH and [d-Cys6, a-aza-Gly10-NH2]-GnRH.

   Click to Show/Hide
Experimental Condition MCF-7 cell; 25 μM
Each Peptide-drug Conjugate Related to This Peptide
Full Information of The Activity Data of The PDC(s) Related to This Peptide
[d-Cys6-des-Gly10-Pro9-NHEt]-GnRH-Dox [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 12 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Cell viability
10%
Administration Time 48 h
Administration Dosage 100 µM
Evaluation Method MTT assay
Description
The results showed that all the conjugates had lower antiproliferative effects than Dox at the tested concentrations (Figure 2A); this may be related to inefficient release of Dox from the conjugate caused by the relative stable thioether bond linkage between Dox-SMP and GnRH analog. The antiproliferative effects of the three conjugates were close at 25, 50, and 75 uM. While at 100 uM, conjugate II exhibited higher inhibitory effect than that of I and III.

   Click to Show/Hide
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Half life period 7.45 h
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Cell viability
28%
Administration Time 48 h
Administration Dosage 75 µM
Evaluation Method MTT assay
MOA of PDC
Although RNT with 177Lu-DOTATATE/PSMA is known as a novel and effective therapy option for cancer that significantly improves the quality of life and survival of patients, it may have acute or chronic side effects. Therefore, any method that can ameliorate these side effects is useful in the RNT process. For this purpose, a few clinical studies have reported that antioxidants as free radical scavengers such as amifostine and vitamins C and E can reduce radioiodine-related side effects, particularly in salivary glands in thyroid cancer patients.

   Click to Show/Hide
Description
The results showed that all the conjugates had lower antiproliferative effects than Dox at the tested concentrations (Figure 2A); this may be related to inefficient release of Dox from the conjugate caused by the relative stable thioether bond linkage between Dox-SMP and GnRH analog. The antiproliferative effects of the three conjugates were close at 25, 50, and 75 uM. While at 100 uM, conjugate II exhibited higher inhibitory effect than that of I and III.

   Click to Show/Hide
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Half life period 7.45 h
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Cell viability
45%
Administration Time 48 h
Administration Dosage 50 µM
Evaluation Method MTT assay
Description
The results showed that all the conjugates had lower antiproliferative effects than Dox at the tested concentrations (Figure 2A); this may be related to inefficient release of Dox from the conjugate caused by the relative stable thioether bond linkage between Dox-SMP and GnRH analog. The antiproliferative effects of the three conjugates were close at 25, 50, and 75 uM. While at 100 uM, conjugate II exhibited higher inhibitory effect than that of I and III.

   Click to Show/Hide
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Half life period 7.45 h
Experiment 4 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Cell viability
48%
Administration Time 48 h
Administration Dosage 100 µM; with 10- µM leuprolide for 2 hours
Description
The combinations of conjugate II and leuprolide exhibited lower antiproliferative efficacy on MCF-7 cells than conjugate II individually at all the tested concentrations (Figure 3A).
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Half life period 7.45 h
Experiment 5 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Cell viability
50%
Administration Time 48 h
Administration Dosage 75 µM; with 10- µM leuprolide for 2 hours
MOA of PDC
Vitamin C as a water-soluble vitamin is the reduced form of ascorbic acid. No significant adverse effect of taking high doses of vitamin C (over 2000 mg/day) has been reported due to the water-soluble feature of vitamin C. Vitamin C directly reacts with hydroxy, alkoxyl, and lipid peroxyl radicals and converts them to alcohol, water, and hydroperoxide lipid, respectively. It has been shown that taking vitamin C before radioiodine therapy can ameliorate the oxidative stress effect of radioiodine. The radioprotective effects of vitamin C are mainly due to its free radical scavenging activity.

   Click to Show/Hide
Description
The combinations of conjugate II and leuprolide exhibited lower antiproliferative efficacy on MCF-7 cells than conjugate II individually at all the tested concentrations (Figure 3A).
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Half life period 7.45 h
Experiment 6 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Cell viability
52%
Administration Time 48 h
Administration Dosage 25 µM
Evaluation Method MTT assay
Description
The results showed that all the conjugates had lower antiproliferative effects than Dox at the tested concentrations (Figure 2A); this may be related to inefficient release of Dox from the conjugate caused by the relative stable thioether bond linkage between Dox-SMP and GnRH analog. The antiproliferative effects of the three conjugates were close at 25, 50, and 75 uM. While at 100 uM, conjugate II exhibited higher inhibitory effect than that of I and III.

   Click to Show/Hide
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Half life period 7.45 h
Experiment 7 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Cell viability
72%
Administration Time 48 h
Administration Dosage 50 µM; with 10- µM leuprolide for 2 hours
Description
The combinations of conjugate II and leuprolide exhibited lower antiproliferative efficacy on MCF-7 cells than conjugate II individually at all the tested concentrations (Figure 3A).
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Half life period 7.45 h
Experiment 8 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Cell viability
75%
Administration Time 48 h
Administration Dosage 100 µM
Evaluation Method MTT assay
Description
However, by linking to [d-Cys6-des-Gly10-Pro9-NHEt]-GnRH, the cytotoxicity of Dox against 3T3 cells was reduced because the cell viability was over 87% after treatment with conjugate II in 25, 50, and 75 uM of equivalent concentration of Dox. Even at 100 uM, conjugate II maintained the cell viability to about 74% (Figure 2B).
In Vitro Model Normal NIH 3T3 cell CVCL_0594
Half life period 7.45 h
Experiment 9 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Cell viability
90%
Administration Time 48 h
Administration Dosage 75 µM
Evaluation Method MTT assay
MOA of PDC
In biological systems, antioxidants such as catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase are responsible for the elimination or reduction of the adverse effects of ROS, that is, they prevent or reduce ROS generation. Dietary antioxidants, such as vitamins E, A, and C, and anthocyanins and polyphenols have a role in the protection of cells against ROS damage.

   Click to Show/Hide
Description
However, by linking to [d-Cys6-des-Gly10-Pro9-NHEt]-GnRH, the cytotoxicity of Dox against 3T3 cells was reduced because the cell viability was over 87% after treatment with conjugate II in 25, 50, and 75 uM of equivalent concentration of Dox. Even at 100 uM, conjugate II maintained the cell viability to about 74% (Figure 2B).
In Vitro Model Normal NIH 3T3 cell CVCL_0594
Half life period 7.45 h
Experiment 10 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Cell viability
92%
Administration Time 48 h
Administration Dosage 50 µM
Evaluation Method MTT assay
Description
However, by linking to [d-Cys6-des-Gly10-Pro9-NHEt]-GnRH, the cytotoxicity of Dox against 3T3 cells was reduced because the cell viability was over 87% after treatment with conjugate II in 25, 50, and 75 uM of equivalent concentration of Dox. Even at 100 uM, conjugate II maintained the cell viability to about 74% (Figure 2B).
In Vitro Model Normal NIH 3T3 cell CVCL_0594
Half life period 7.45 h
Experiment 11 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Cell viability
98%
Administration Time 48 h
Administration Dosage 25 µM
Evaluation Method MTT assay
Description
However, by linking to [d-Cys6-des-Gly10-Pro9-NHEt]-GnRH, the cytotoxicity of Dox against 3T3 cells was reduced because the cell viability was over 87% after treatment with conjugate II in 25, 50, and 75 uM of equivalent concentration of Dox. Even at 100 uM, conjugate II maintained the cell viability to about 74% (Figure 2B).
In Vitro Model Normal NIH 3T3 cell CVCL_0594
Half life period 7.45 h
Experiment 12 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Cell viability
108%
Administration Time 48 h
Administration Dosage 25 µM; with 10- µM leuprolide for 2 hours
Description
The combinations of conjugate II and leuprolide exhibited lower antiproliferative efficacy on MCF-7 cells than conjugate II individually at all the tested concentrations (Figure 3A).
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Half life period 7.45 h
References
Ref 1 Synthesis, in vitro stability, and antiproliferative effect of d-cysteine modified GnRH-doxorubicin conjugates. J Pept Sci. 2019 Jan;25(1):e3135. doi: 10.1002/psc.3135. Epub 2018 Nov 22.