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Topoisomerase inhibitorsNever marketedNatural productNeeds review

Camptothecin

Also known as CPT, Camptothecin sodium

A plant alkaloid first isolated from Camptotheca acuminata. Its water-soluble sodium salt was introduced in early trials in the 1960s but was highly toxic in animals; irinotecan and topotecan are semisynthetic derivatives.

From discovery to approval

  1. 1966 · First described

    A 2004 article credits Monroe Wall and Mansukh Wani of Research Triangle Institute with first isolating and identifying camptothecin from Camptotheca acuminata. Their 1966 paper in the Journal of the American Chemical Society reports its isolation and structure (title only); Wall's 1995 lecture abstract says the plant is native to China.[2][3][4][5]

  2. No approval is recorded on this site.

How it works

Camptothecin was shown in 1985 to induce protein-linked DNA breaks through mammalian DNA topoisomerase I. The authors proposed that it blocks the rejoining step of the enzyme's breakage-reunion reaction, so that a cleavable complex accumulates.[1]

Where it came from and why

The 1966 title calls camptothecin a novel alkaloidal leukemia and tumor inhibitor, and Wall's 1995 lecture abstract says it was isolated by bioassay-guided fractionation of plant extracts. The abstracts cited do not describe the screening programme that supplied the plant material.

Cancers

  • Leukaemia and solid tumours (experimental)

    The 1966 isolation paper's title describes camptothecin as a novel alkaloidal leukemia and tumor inhibitor; the paper is cited by title only.[2]

  • Breast, lung and colorectal cancer (through analogues)

    Wall's 1995 lecture abstract says camptothecin and its analogues, alone or with cisplatin, show efficacy against solid tumours of the breast, lung and colorectum.[4]

Family and partners

Drugs derived from it: Irinotecan, Topotecan, Belotecan

Worth knowing

  • Camptothecin's target, topoisomerase I, was reported in 1985, roughly two decades after its isolation was published in 1966.[1]
  • A 2006 review says the water-soluble sodium salt used in early trials in the 1960s was highly toxic in animals, whereas the semisynthetic derivatives irinotecan and topotecan did not cause haemorrhagic cystitis.[5]
  • A 2004 article credits the same Research Triangle Institute team, Wall and Wani, with also discovering taxol, first isolated and identified from Taxus brevifolia.[3]
  • A 2025 review says that, among camptothecin analogues, only topotecan and irinotecan have been approved by the US Food and Drug Administration.[6]

References

  1. Hsiang YH, Hertzberg R, Hecht S, Liu LF. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem. 1985;260(27):14873-8. PubMed
  2. Wall ME, Wani MC, Cook CE, Palmer KH, McPhail AT, Sim GA. Plant Antitumor Agents. I. The Isolation and Structure of Camptothecin, a Novel Alkaloidal Leukemia and Tumor Inhibitor from Camptotheca acuminata. Journal of the American Chemical Society. 1966;88(16):3888-3890. DOI
  3. Oberlies NH, Kroll DJ. Camptothecin and taxol: historic achievements in natural products research. J Nat Prod. 2004;67(2):129-35. PubMedDOI
  4. Wall ME, Wani MC. Camptothecin and taxol: discovery to clinic--thirteenth Bruce F. Cain Memorial Award Lecture. Cancer Res. 1995;55(4):753-60. PubMed
  5. Hartmann JT, Lipp HP. Camptothecin and podophyllotoxin derivatives: inhibitors of topoisomerase I and II - mechanisms of action, pharmacokinetics and toxicity profile. Drug Saf. 2006;29(3):209-30. PubMedDOI
  6. Gong J, Zhang W, Balthasar JP. Camptothein-Based Anti-Cancer Therapies and Strategies to Improve Their Therapeutic Index. Cancers (Basel). 2025;17(6). PubMedDOI