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Bending the Curve Trial by Trial
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Pyrimidine analogues and fluoropyrimidinesUsed in a few countriesDerivative of an earlier drugNeeds review

Enocitabine

Also known as BH-AC, N4-behenoyl-1-beta-D-arabinofuranosylcytosine, behenoyl cytarabine

An N4-behenoyl derivative of cytarabine (BH-AC). A 2002 review lists it among cytarabine derivatives used clinically in Japan, and a Japan Leukemia Study Group trial tested it in acute myeloid leukaemia.

From discovery to approval

  1. 1976 · First described

    A 1976 Cancer Research paper by Aoshima and colleagues reports 50 newly synthesised cytarabine derivatives tested in mouse L1210 leukaemia. N4-acyl derivatives with long-chain saturated fatty acids were highly active, including N4-behenoyl-cytarabine.[1][2][3]

  2. No approval is recorded on this site.

How it works

It is a long-chain acyl derivative of cytarabine that, in the 1976 report, resisted cytidine deaminase, the enzyme that inactivates cytarabine; cytarabine itself acts as described for that drug.[1]

Where it came from and why

The 1976 abstract says the best derivatives were active at smaller doses than cytarabine whatever the schedule, and were resistant to cytidine deaminase, which inactivates cytarabine. A 2002 review links the search for derivatives to cytarabine's rapid deamination.

Cancers

  • Acute myeloid leukaemia

    A Japan Leukemia Study Group randomised trial of 341 registered adults compared remission induction and consolidation with behenoyl cytarabine (BHAC) and with cytarabine.[4]

Family and partners

Derived from: Cytarabine

Worth knowing

  • In the Japan Leukemia Study Group trial, complete remission was 72% with behenoyl cytarabine and 81% with cytarabine (P = .035), and the predicted 55-month event-free survival was 23% and 35% (P = .0253), so the authors concluded behenoyl cytarabine gave poorer results at the doses and schedules tested.[4]
  • A 2002 review lists ancitabine, enocitabine and cytarabine ocfosfate as cytarabine derivatives that have been used clinically in Japan.[2]
  • A 1990 paper names N4-behenoyl-1-beta-D-arabinofuranosylcytosine as enocitabine (BH-AC) and describes it as an antileukemic drug that inhibited the replication of human cytomegalovirus in vitro.[3]

References

  1. Aoshima M, Tsukagoshi S, Sakurai Y, Oh-ishi J, Ishida T. Antitumor activities of newly synthesized N4-acyl-1-beta-D-arabinofuranosylcytosine. Cancer Res. 1976;36(8):2726-32. PubMed
  2. Hamada A, Kawaguchi T, Nakano M. Clinical pharmacokinetics of cytarabine formulations. Clin Pharmacokinet. 2002;41(10):705-18. PubMedDOI
  3. Nakamura K, Eizuru Y, Kumura K, Minamishima Y. Antiviral effect of antileukemic drugs N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC) and 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine (cyclo-C) against human cytomegalovirus. J Med Virol. 1990;31(2):141-7. PubMedDOI
  4. Kobayashi T, Miyawaki S, Tanimoto M, Kuriyama K, Murakami H, Yoshida M, et al. Randomized trials between behenoyl cytarabine and cytarabine in combination induction and consolidation therapy, and with or without ubenimex after maintenance/intensification therapy in adult acute myeloid leukemia. The Japan Leukemia Study Group. J Clin Oncol. 1996;14(1):204-13. PubMedDOI