Peptide-drug Conjugate Information

General Information of This Peptide-drug Conjugate (PDC)
PDC ID
PDC_00023
PDC Name
111In-DTPA-octreotide
Synonyms
OctreoScan; 111In-DTPA-octreotide; Sdz-215-811; 111In-Pentetreotide; Neuroendomedix; Somatother; SDZ-215811s
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PDC Status
Approved
Indication
In total 1 Indication(s)
Digestive system neoplasms
Structure
Peptide Name
Octreotide
  Peptide Info 
Receptor Name
Somatostatin receptor type 1 (SSTR1)
  Receptor Info 
Drug Name
Indium-111
  Drug Info 
Therapeutic Target
Human Deoxyribonucleic acid (hDNA)
  Target Info 
Linker Name
Amide bond
  Linker Info 
Peptide Modified Type
Amino acid modifications; Cyclization modification
Modified Segment
D-amino acids
Ternimal Modification
N-terminal modification
Drugbank ID
DB11835
ChEBI ID
CHEMBL1200642
Formula
C63H84InN13O19S2
#Ro5 Violations (Lipinski): 4 Molecular Weight (mw) 1502.5
Lipid-water partition coefficient (xlogp) Not Available
Hydrogen Bond Donor Count (hbonddonor) 14
Hydrogen Bond Acceptor Count (hbondacc) 25
Rotatable Bond Count (rotbonds) 31
Full List of Activity Data of This Peptide-drug Conjugate
Obtained from the Model Organism Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Digestive system neoplasms
Efficacy Data Tumor cell uptake rate
47%
Administration Time 4 h
Administration Dosage 10 nM
MOA of PDC
In our previous study, d-Phe at position 1 in 111In-DTPA-d-Phe1-octreotide was replaced with Asp to minimize the change in molecular size. While the Phe3D-Trp4Lys5Thr6 sequence in octreotide is important for binding to the somatostatin receptor, the majority of octreotide derivatives with high somatostatin receptor affinity possess an N-terminal amino acid with an aromatic side chain, such as d-Phe or naphthylalanine. With these findings in mind, we designed, synthesized and evaluated not only the previously reported 111In-DTPA-Asp1-octreotide but also 111In-DTPA-Asp0-d-Phe1-octreotide, in which an Asp was incorporated between DTPA and N-terminal d-Phe in 111In-DTPA-d-Phe1-octreotide.

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Description
Figure 3 shows the results of cellular uptake experiments. When incubated with111In-DTPA-Asp1-octreotide, the uptake levels of radioactivity by AR42J cells were extremely low compared with those for111In-DTPA-d-Phe1-octreotide. In contrast, the uptake levels of111In-DTPA-Asp0-d-Phe1-octreotide increased in a time-dependent manner. The uptake levels of111In-DTPA-Asp0-d-Phe1-octreotide were not significantly different from those for111In-DTPA-d-Phe1-octreotide at 4h. For 111In-DTPA-Asp0-d-Phe1-octreotide, cell uptake experiments were conducted in the presence of varying concentrations of an unmodified octreotide. In Figure 4, uptake levels are shown as a percentage of the radioactivity level in the absence of the unmodified octreotide. The uptake levels of 111In-DTPA-Asp0-d-Phe1-octreotide were reduced in association with the concentration of the unmodified octreotide. The radioactivity uptake level was reduced by approximately 90% at 1 M concentration of the octreotide.

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In Vivo Model AR42J tumor-bearing mice model.
References
Ref 1 Design, synthesis and biological evaluation of negatively charged In-DTPA-octreotide derivatives. Bioorg Med Chem. 2014 Feb 15;22(4):1377-82. doi: 10.1016/j.bmc.2013.12.063. Epub 2014 Jan 8.