CB 3703
CB 3703 is an inhibitor of thymidylate synthase (TS) and dihydrofolate reductase (DHFR). CB 3703 has an IC50 of 0.25 μM against rat TS, a Ki of 0.47 μM against mouse TS, an IC50 of 6.8 nM against rat DHFR, and a Ki of 0.6 pM against mouse DHFR. CB 3703 is transported via the reduced folate pathway, has a short plasma half-life, and can prolong the survival of tumor-bearing mice. CB 3703 can be used in the research of L1210 ascites tumors.
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- CAS No.: 32093-09-7
- Formule: C22H24N6O5
- Masse moléculaire:452.46
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| L1210 | IC50 |
0.019 μM
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Growth inhibition against mouse L1210 cells assessed as reduction in cell count after 48 hr incubation.
Growth inhibition against mouse L1210 cells assessed as reduction in cell count after 48 hr incubation.
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0014296480902145 |
In Vitro
CB 3703 (6.8 nM-100 μM) potently inhibits rat liver DHFR (I50=6.8 nM) and Yoshida ascites sarcoma TS (I50=0.25 μM), and weakly inhibits other folate metabolizing enzymes at 100 μM[1].
CB 3703 potently inhibits purified L1210 cell DHFR (Ki=0.6 pM, competitive) and purified L1210 cell TS (Ki=0.47 μM, non-competitive), and weakly inhibits rat liver methionine synthetase (Ki=0.36 mM)[1].
CB 3703 (50 nM; 48 hr) toxicity to L1210 cells is partially reversed by thymidine or folinic acid alone, improved by their combination, and fully reversed only by thymidine plus hypoxanthine[1].
CB 3703 (0.019 μM; 48 hr) inhibits L1210 cell growth with an I50 of 0.019 μM[1].
CB 3703 (2-40 μM; 20 min) competes with methotrexate for uptake into L1210 cells, and weakly competes with folic acid, suggesting shared transport pathways[1].
CB 3703 (4 μM; 0-40 min) accumulates to ~10-fold higher intracellular levels than methotrexate in L1210 cells over 40 minutes, does not plateau within this time, and does not use the folic acid transport pathway[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:L1210 cells
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Concentration:0.019 μM
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Incubation Time:48 hr
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Result:Reduced L1210 cell count to 50% of control levels after 48 hr incubation at 0.019 μM.
Parmacokinetics
| Species | Dose | Route | T1/2 | Plasma Concentration |
|---|---|---|---|---|
| Mice[1] | 10 mg/kg | i.p. | 1.54 h | 0.05 μM |
In Vivo
CB 3703 (1-8 mg/kg; i.p.; single dose) has an LD50 between 2 mg/kg and 4 mg/kg in healthy female (DBA2×C57B1)F1 mice following a single i.p. dose[1].
CB 3703 (10 mg/kg; i.p.; single dose) exhibits a plasma half-life of 1.54 hours in healthy female (DBA2×C57B1)F1 mice following a single 10 mg/kg i.p. dose, with barely detectable levels at 24 hours[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:(DBA2×C57B1)F1 hybrid (9-12-week-old female; L1210 leukaemia ascites model, injected i.p. with 5×104 tumour cells 3 days prior to treatment)[1]
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Dosage:1 mg/kg; 2 mg/kg; 4 mg/kg; 8 mg/kg
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Administration:i.p.; single dose
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Result:Produced a 36% increase in median survival time (from 14 days in untreated controls to 19 days).
Produced a 64% increase in median survival time (to 23 days).
Caused 3/5 tumour-bearing mice to die from toxicity before 10 days.
Caused all 5 tumour-bearing mice to die from toxicity before 10 days.
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Animal Model:(DBA2×C57B1)F1 hybrid (9-12-week-old female; healthy, non-tumour bearing)[1]
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Dosage:1 mg/kg; 2 mg/kg; 4 mg/kg; 8 mg/kg
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Administration:i.p.; single dose
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Result:Caused 5/11 mice to die from toxicity.
Caused 1/10 mice to die from toxicity.
Caused all 10 mice to die from toxicity.
Caused all 10 mice to die from toxicity.
Resulted in an LD50 between 2 mg/kg and 4 mg/kg.
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Animal Model:(DBA2×C57B1)F1 hybrid (9-12-week-old female; healthy, non-tumour bearing)[1]
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Dosage:10 mg/kg
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Administration:i.p.; single dose
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Result:Exhibited exponential plasma level decay over the first 8 hours with a half-life of 1.54 hours.
Reached barely detectable plasma levels of approximately 0.05 μM at 24 hours.
Chemical Information
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CAS No. 32093-09-7
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Masse moléculaire 452.46
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Formule C22H24N6O5
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SMILES
O=C(O)CC[C@@H](C(O)=O)NC(C1=CC=C(NCC2=C(C)C3=C(N)N=C(N)N=C3C=C2)C=C1)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CB 3703 Related Classifications
HY-119143 Related Classifications
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