Approval Year
| Substance Class |
Protein
Created
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admin
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Sat Dec 16 14:04:20 GMT 2023
by
admin
on
Sat Dec 16 14:04:20 GMT 2023
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| Protein Sub Type | |
| Sequence Type | COMPLETE |
| Record UNII |
H4QZU9L323
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| Record Status |
Validated (UNII)
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| Record Version |
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Code | English |
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FDA ORPHAN DRUG |
507415
Created by
admin on Sat Dec 16 14:04:20 GMT 2023 , Edited by admin on Sat Dec 16 14:04:20 GMT 2023
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| Code System | Code | Type | Description | ||
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897026-25-4
Created by
admin on Sat Dec 16 14:04:20 GMT 2023 , Edited by admin on Sat Dec 16 14:04:20 GMT 2023
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745104
Created by
admin on Sat Dec 16 14:04:20 GMT 2023 , Edited by admin on Sat Dec 16 14:04:20 GMT 2023
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C85480
Created by
admin on Sat Dec 16 14:04:20 GMT 2023 , Edited by admin on Sat Dec 16 14:04:20 GMT 2023
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PRIMARY | azurin-derived cell-penetrating peptide p28: A water-soluble, amphipathic, 28 amino acid (amino acids 50-77), 2.9 kD fragment peptide (p28) derived from the protein azurin with potential antineoplastic and antiangiogenic activities. Although the mechanism has yet to be fully elucidated, the preferential cellular uptake of azurin-derived cell-penetrating peptide p28 by tumor cells and endothelial cells is likely via caveolae-mediated endocytosisthe C-terminal 18 amino acid residues (50-67) appear to responsible for this preferential uptake. After cell entry, the first 12 amino acid residues interact with tumor suppressor p53 and form a p28:p53 complex, which may result in a reduction of proteasomal degradation of p53, increased p53 levels, and p53-mediated cell cycle inhibition and apoptosis. Azurin is a cupredoxin secreted by the bacterium Pseudomonas aeruginosa. Cell penetrating peptides (CPPs) are cationic and/or amphipathic peptides, typically less than 30 amino acids in length, that can penetrate cell membranes easily and may transport molecular cargo. Check for active clinical trials using this agent. (NCI Thesaurus) | ||
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H4QZU9L323
Created by
admin on Sat Dec 16 14:04:20 GMT 2023 , Edited by admin on Sat Dec 16 14:04:20 GMT 2023
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PRIMARY |
| Related Record | Type | Details | ||
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ACTIVE MOIETY |
Originator: CDG Therapeutics; Developer: CDG Therapeutics, Pediatric Brain Tumor Consortium, University of Illinois at Chicago; Class: Antineoplastic, Peptide; Mechanism of Action: Tumour suppressor protein p53 modulator, Ubiquitin-protein ligase inhibitor; Orphan Drug Status: No; On Fast track: No; New Molecular Entity: Yes; Available For Licensing: Yes; Highest Development Phases: Phase I for CNS cancer, No development reported for HIV infections, Solid tumours; Most Recent Events: 16 Jul 2016 No recent reports of development identified for phase-I development in Solid-tumours(Second-line therapy or greater, In adults) in USA (IV, Infusion),
16 Jul 2016 No recent reports of development identified for preclinical development in HIV-infections in USA (Parenteral), 07 Jun 2011 Interim adverse events, efficacy and pharmacokinetics data from a phase I trial in Solid tumours released byCDG Therapeutics
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ACTIVE MOIETY |
BACKGROUND: A 28 amino-acid (aa) cell-penetrating peptide (p28) derived from azurin, a redox protein secreted from the opportunistic pathogen Pseudomonas aeruginosa, produces a post-translational increase in p53 in cancer cells by inhibiting its ubiquitination.
RESULTS: The L1 loop (aa 112-124), a region within the S7-S8 loop (aa 214-236) and T140, P142, Q144, W146, R282 and L289 of the p53DBD were identified as potential sites for p28 binding. p28 decreased the level of the E3 ligase COP1 >80%, in p53wt and p53mut cells with no decrease in COP1 in p53dom/neg or p53null cells. Brief increases in the expression of the E3 ligases, TOPORS, Pirh2 and HDM2 (human double minute 2) in p53wt and p53mut cells were in response to sustained increases in p53.
CONCLUSION: These data identify the specific motifs within the DBD of p53 that bind p28 and suggest that p28 inhibition of COP1 binding results in the sustained, post-translational increase in p53 levels and subsequent inhibition of cancer cell growth independent of an HDM2 pathway.
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| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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| Molecular Formula | CHEMICAL |
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| MOL_WEIGHT:NUMBER(CALCULATED) | CHEMICAL |
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