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  4. JNJ-27548547

JNJ-27548547, Mitomycin C (HY-13316) prodrug, is a Mitomycin C and lipophilic group conjugate. JNJ-27548547 undergoes thiolytic cleavage of its dithiobenzyl linker in the presence of reducing agents to release active substance Mitomycin C. JNJ-27548547 is formulated into pegylated liposomes (PL-MLP) with high antitumor activity in mice models.

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JNJ-27548547

JNJ-27548547 Chemical Structure

CAS No. : 303983-00-8

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Description

JNJ-27548547, Mitomycin C (HY-13316) prodrug, is a Mitomycin C and lipophilic group conjugate. JNJ-27548547 undergoes thiolytic cleavage of its dithiobenzyl linker in the presence of reducing agents to release active substance Mitomycin C. JNJ-27548547 is formulated into pegylated liposomes (PL-MLP) with high antitumor activity in mice models[1].

In Vitro

Pegylated liposomal JNJ-27548547 (Compound PL-MLP) (72 h) has substantially reduced in vitro cytotoxicity against mouse M109 carcinoma cells under standard conditions, but its cytotoxicity increases up to 6-fold to near-free MMC levels when co-incubated with 0.25-1.0 mM Cysteine (HY-Y0337) or N-acetyl-cysteine (HY-B0215) (72 h)[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

JNJ-27548547 Related Antibodies

Cell Cytotoxicity Assay[1]

Cell Line: mouse M109 carcinoma cells
Concentration: MMC equivalents (PL-MLP); 0.25-1.0 mM cysteine; 0.25-1.0 mM N-acetyl-cysteine; 0.25-1.0 mM mesna
Incubation Time: 72 h (PL-MLP continuous exposure); 72 h (co-incubation with reducing agents)
Result: Exhibited 5- to 6-fold less cytotoxicity than free mitomycin C (MMC) under standard conditions.
Increased cytotoxic activity by up to 6-fold, reaching levels nearly comparable to free MMC, when co-incubated with 0.25 to 1.0 mM cysteine or N-acetyl-cysteine.
In Vivo

Pegylated liposomal JNJ-27548547 (Compound PL-MLP) (2-5 mg/kg; i.v.; at day 7 or 2-4 mg/kg; at day 7, 14, 21 or 6 mg/kg; at day 5, 12, 19) demonstrates dose-dependent antitumor activity in the M109 lung carcinoma footpad model[1].
Pegylated liposomal JNJ-27548547 (4-8 mg/kg; i.v.; single dose, day 5 after tumor inoculation) demonstrates significant antitumor activity in the C26 colon carcinoma model[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Lung carcinoma BALB/c mice (female, 8 weeks old, M109 lung carcinoma cells inoculated into hind footpad at 10^6 cells per mouse)[1]
Dosage: 2, 5 mg/kg (single dose); 2, 4 mg/kg (3 doses); 6 mg/kg (2-3 doses)
Administration: i.v.; single dose (day 7); 3 doses (days 7, 14, 21); 2 doses (days 5, 12); 2-3 doses (days 5, 12, 19)
Result: Extended median time to tumor >5 mm or death to 27 days; yielded 0% cures and 0% toxic deaths (n=20).
Extended median time to tumor >5 mm or death to 32 days; yielded 0% cures and 0% toxic deaths (n=21).
Extended median time to tumor >5 mm or death to 34 days; yielded 0% cures and 0% toxic deaths (n=10).
Extended median time to tumor >5 mm or death to 44 days; yielded 0% cures and 0% toxic deaths (n=10).
Extended median time to tumor >5 mm or death to 61 days; yielded 0% cures and 0% toxic deaths (n=10).
Extended median time to tumor >5 mm or death to 62 days; yielded 30% cures and 0% toxic deaths (n=20).
Molecular Weight

1139.59

Formula

C62H98N4O11S2
CAS No.
SMILES

CO[C@]12[C@]3([H])[C@@](CN1C4=C(C(C(N)=C(C4=O)C)=O)[C@H]2COC(N)=O)([H])N3C(OCC5=CC=C(SSCC(OC(CCCCCCCCCCCCCCCCC)=O)COC(CCCCCCCCCCCCCCCCC)=O)C=C5)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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JNJ-27548547 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

JNJ-27548547303983-00-8JNJ27548547JNJ 27548547Drug IntermediateDrug IintermediateBALB/c miceSprague-Dawley ratsC26colon carcinomareducing agentsM109 carcinomamitomycin CM109Rpegylated liposomescarcinomaInhibitorinhibitorinhibit

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