L 377202
L 377202 is a conjugate of Doxorubicin (HY-15142A) and a PSA substrate peptide. L 377202 is cleaved at its peptide precursor portion by prostate-specific antigen PSA, releasing N-(L-leucyl) doxorubicin and cytotoxic Doxorubicin. L 377202 is internalized via endocytosis and endosomal escape. L 377202 can be used for research on prostate cancer.
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- No. CAS: 207395-85-5
- Fòrmula: C65H89N9O25
- Peso molecular:1396.45
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
Descripciòn
In Vitro
L 377202 (Dox-PSA) (40 μM; up to 24 h) is efficiently hydrolyzed by PSA with enzymatic activity, with a hydrolysis rate of >94% and no temperature dependence[6].
LTSL loaded with L 377202 (Dox-PSA) (48-96 h) combined with mild HT significantly reduces C4-2B spheroid viability, whereas free L 377202 is less effective[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:C4-2B prostate cancer cell monolayers
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Concentration:Range of concentrations (free Dox-PSA or Dox-PSA-loaded LTSL)
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Incubation Time:24-96 h post-incubation; 4 h (resazurin); 42°C HT
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Result:LTSL substantially reduced toxicity at 37°C, whereas exposure to 42°C significantly boosted liposomal toxicity in a dose-dependent fashion.
Cell viability was comparable at 37°C and 42°C.
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Cell Line:C4-2B spheroids
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Concentration:Range of concentrations (free Dox-PSA or Dox-PSA-loaded LTSL)
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Incubation Time:48-96 h post-exposure; 30 min (EDTA); overnight (resazurin)
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Result:Loaded LTSL in combination with 42°C significantly decreased spheroid viability across all the time points tested.
Toxicity was lower in spheroids, and mild HT did not significantly alter the toxicity profile.
In Vivo
L 377202-loaded LTSL (equivalent to 10 mg/kg L 377202; i.v.; repeated three times) combined with HT delays metastatic growth in the C4-2B-4 bone metastasis model in mice[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NSG (male, 8 weeks old)[6]
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Dosage:equivalent to 10 mg/kg
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Administration:i.v.; repeated three times with 3-4-day intervals
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Result:Produced 64% tumor volume reduction over control at day 31, with tumors reaching volumes comparable to those in the unencapsulated formulation group.
Produced almost 3-fold reduction in tumor volume compared with the group without HT.
Did not delay tumor growth relative to control.
Produced similar tumor growth retardation with and without HT.
Median survival was 47 days for the liposomal formulation with HT, 43 days for the unencapsulated formulation with HT, and 37 days for the liposomal formulation without HT.
The unencapsulated formulation with HT did not prolong survival over the unencapsulated formulation without HT.
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Animal Model:NSG (male, 8 weeks old)[6]
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Dosage:equivalent to 10 mg/kg
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Administration:i.v.; repeated three times
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Result:Delayed metastatic growth in vivo, as shown by bioluminescence imaging on days 14, 19, and 22.
Ensayo clínico
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 207395-85-5
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Peso molecular 1396.45
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Fòrmula C65H89N9O25
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SMILES
OC1=C2C([C@H](C[C@@](C(CO)=O)(O)C2)O[C@@]3([H])C[C@@H]([C@H](O)[C@H](C)O3)NC([C@H](CC(C)C)NC([C@H](CO)NC([C@H](CCC(N)=O)NC([C@H](C4CCCCC4)NC([C@H](CO)NC([C@H](C)NC([C@H]5N(C[C@H](O)C5)C(CCCC(O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=C(O)C6=C1C(C7=CC=CC(OC)=C7C6=O)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Graeser R, et al. Synthesis and biological evaluation of an albumin-binding prodrug of doxorubicin that is cleaved by prostate-specific antigen (PSA) in a PSA-positive orthotopic prostate carcinoma model (LNCaP). International journal of cancer. 2008 Mar 01;122(5):1145-54. [Content Brief]
[4]. Denny WA, et al. Tumor-activated prodrugs--a new approach to cancer therapy. Cancer investigation. 2004;22(4):604-19. [Content Brief]
[6]. Pereira S, et al. Encapsulation of doxorubicin prodrug in heat-triggered liposomes overcomes off-target activation for advanced prostate cancer therapy. Acta biomaterialia. 2022 Mar 01;140:530-546. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
L 377202 Related Classifications
HY-106195 Related Classifications
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