Peptide-drug Conjugate Information
General Information of This Peptide-drug Conjugate (PDC)
| PDC ID |
PDC_02144
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| PDC Name |
JF-10-71
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| PDC Status |
Investigative
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| Indication |
In total 1 Indication(s)
Neuroblastoma
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| Structure |
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| Peptide Name |
Potent somatostatin analog (SSA)
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Peptide Info | ||||
| Receptor Name |
Somatostatin receptor type 2 (SSTR2)
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Receptor Info | ||||
| Drug Name |
Camptothecin
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Drug Info | ||||
| Therapeutic Target |
DNA topoisomerase 1 (TOP1)
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Target Info | ||||
| Linker Name |
N-(2-aminoethyl)-N-carboxyglycine
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Linker Info | ||||
| Peptide Modified Type |
Cyclization modification
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| Modified Segment |
Side-chain cyclization
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| ChEBI ID | ||||||
Full List of Activity Data of This Peptide-drug Conjugate
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Data of This PDC | [1], [2] | ||||
| Indication | Neuroblastoma | ||||
| Efficacy Data | Half maximal inhibitory concentration (IC50) |
1363 nM
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| Administration Time | 3 days | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
In a previous study, we used a potent somatostatin analog (SSA) with high affinity for SSTR2 for attachment to an antisense peptide nucleic acid (PNA) directed against the n-myc oncogene and showed that PNA-SSA conjugates produced receptor-specific inhibition of cell growth. Cleavable-linker chemistry was then developed that allowed this approach to be extended to well-known cytotoxic compounds such as camptothecin and combretastatin. In the present report two CPT-SSA conjugates, JF-10-71 and JF-10-81, displaying differing stabilities were chosen to potentially treat SSTR2-positive rat pancreatic CA20948 tumors in Lewis rats and SCLC NCI-H69 tumors in athymic nude mice.
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| Description |
Previously, a series of CPT-SSA conjugates were tested for their stability in phosphate buffer/rat plasma and in vitro inhibitory activity in tumor cell growth (data not shown). Two of these conjugates, JF-10-71 and JF-10-81, displaying higher and lower stability, respectively, were chosen for further experiments in serial tumor cell lines. Also, free CPT and SSA itself were tested as controls. The results (Table 1) show that the IC50 values increased compared with CPT to JF-10-81 and further to JF-10-71 with the exception of the CA20948 cells. CPT and both conjugates were particularly effective in SSTR2-overexpressing IMR32 cells displaying IC50 values 3.1, 64.13, and 282.50 nM, respectively. SSTR2-overexpressing CA20948 cells were poorly responsive to CPT itself (IC50, 3077 nM); however, its somatostatin conjugates were actually more potent (IC50: JF-10-81, 1790 nM; JF-10-71, 1363 nM). SSA itself exhibited little effect on growth of all tested cell lines even at doses up to 10-5 M.
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References