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Cancer Chemotherapy and Pharmacology

, Volume 29, Issue 3, pp 190–194 | Cite as

Antitumor drug cross-resistance in vivo in a murine P388 leukemia resistant to ethyl 5-amino-1,2-dihydro-2-methyl-3-phenylpyrido[3,4-b]pyrazin-7-ylcarbamate 2-hydroxyethanesulfonate hydrate (NSC 370 147) 370 147

  • William R. Waud
  • Steadman D. HarrisonJr.
  • Carroll G. TempleJr
  • Daniel P. GriswoldJr.
Original Articles Cross-Resistance, P388 Leukemia, NSC 370147

Summary

Ethyl 5-amino-1,2-dihydro-2-methyl-3-phenylpyrido[3,4-b]pyrazin-7-ylcarbamate 2-hydroxyethanesulfonate hydrate (NSC 370 147) is a potent mitotic inhibitor, which has provided the basis for a candidate for clinical trial. As observed with clinically useful drugs, the development of clinical resistance to NSC 370 147 will probably be encountered. Information concerning resistance to NSC 370 147 should aid in the design of strategies for the opitmal clinical use of the drug. A P388 leukemia resistant to NSC 370 147 (P388/NSC 370 147) was isolated and its in vivo cross-resistance profile was determined. The P388/NSC 370 147 line was cross-resistant to vincristine but was not cross-resistant to doxorubicin, etoposide, cisplatin, melphalan, methotrexate, or 5-fluorouracil. This information plus other in vivo cross-resistance data [Waud et al. (1990) Cancer Res 50: 3239] suggests that NSC 370 147 may be useful in non-cross-resistant combinations with doxorubicin, melphalan, cisplatin, or methotrexate. The lack of cross-resistance of P388/NSC 370 147 to doxorubicin and etoposide shows that resistance to NSC 370 147 does not involve multidrug resistance and suggests that themdr1 gene is not involved in resistance to NSC 370 147.

Keywords

Ethyl Hydrate Leukemia Cancer Research Doxorubicin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

LD10

dosage level producing 10% lethality

P388/NSC 370 147

P388 leukemia resistant to NSC 370 147

P388/O

P388 reukemia sensitive to NSC 370 147

qd

daily

q3hx3

every 3 h for a total of three injections

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References

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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • William R. Waud
    • 1
  • Steadman D. HarrisonJr.
    • 1
  • Carroll G. TempleJr
    • 2
  • Daniel P. GriswoldJr.
    • 1
  1. 1.Chemotherapy and Toxicology ResearchSouthern Research InstituteBirminghamUSA
  2. 2.Organic Chemistry ResearchSouthern Research InstituteBirminghamUSA

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