What molecule am I?
Camptothecin1 is an alkaloid that was isolated in 1966 from the stems and bark of the Chinese tree Camptotheca acuminata by Monroe E. Wall at Research Triangle Institute (RTI; Durham, NC) and colleagues there and at the University of Illinois (Urbana–Champaign). Portions of the tree had been used in traditional Chinese medicine to treat leukemia and other cancerous tumors.
In 1969, the Wall team at RTI described a first approach to synthesizing camptothecin. Six years later, E. J. Corey and co-workers at Harvard University (Cambridge, MA) reported its total synthesis via a convergent nine-step procedure in which the five-ring structure was formed in the last step.
Camptothecin’s mode of action is inhibition of DNA topoisomerases: enzymes that change DNA topology, which often leads to the formation of cancer cells. It has been developed as a cancer therapy; but because of pharmacological and side-effect problems, several derivatives have been developed and approved by the US Food and Drug Administration for treating cancer. These include irinotecan2 (approved in 1996), topotecan3 (2007), and trastuzumab deruxtecan4 (2019).
For additional information about camptothecin, see the ScienceDirect topics page on the molecule.
1. SciFindern name: 1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione, 4-ethyl-4-hydroxy-.
2. CAS Reg. No. 97682-44-5.
3. CAS Reg. No. 123948-87-8.
4. CAS Reg. No. 1826843-81-5.
Camptothecin hazard information
| Hazard class* | GHS code and hazard statement | |
|---|---|---|
| Acute toxicity, oral, category 3 | H301—Toxic if swallowed |  |
| Germ cell mutagenicity, category 1B | H340—May cause genetic defects |  |
*Globally Harmonized System (GHS) of Classification and Labeling of Chemicals. Explanation of pictograms.
ABBV-CLS-4841 (AC484, osunprotafib) is a thiadiazolidinone dioxide2 derivative developed at AbbVie (North Chicago, IL), Calico Life Sciences (South San Francisco, CA), and the Broad Institute of MIT and Harvard (Cambridge, MA). It is a protein tyrosine phosphatase (PTP) inhibitor designed to make difficult targets in cancer cells more accessible.
AC484 and similar compounds were first described in 2020 in US Patent 10,851,073 to inventors Geoff T. Halvorsen, Jennifer M. Frost, and Philip R. Kym at Abbvie. The patent’s abstract states that the compounds are “for treating diseases, disorders, and conditions favorably responsive to [PTP] inhibitor treatment, e.g., a cancer or a metabolic disease.”
In July 2023, Florian Wiede, Tony Tiganis, and co-workers at Monash University (Clayton, Australia) and collaborators there and at other Australian and American institutions reported that AC484 inhibits PTP classes 1B and N2 and enhances T cell ani-tumor immunity. The following October, a large team of researchers at Abbvie, Calico, and the Broad Institute described the details of the discovery of AC484, its immune cell activation, and its control of tumor growth.
For more information, go to accounts of AC484’s ability to promote cancer immunotherapy by Junyu Wang, Shugang Qin*, and Anren Zhang* at two Chinese universities and Brianna Barbu at C&EN.
1. CAS Reg. No. 2489404-97-7; SciFindern name: 1,2,5-thiadiazolidin-3-one, 5-{(7R)-1-fluoro-5,6,7,8-tetrahydro-3-hydroxy-7-[(3-methylbutyl)amino]-2-naphthalenyl}-, 1,1-dioxide.
2. CAS Reg. No. 883050-24-6.
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Camptothecin fast facts
| CAS Reg. No. | 7689-03-4 |
| Empirical formula | C20H16N2O4 |
| Molar mass | 348.35 g/mol |
| Appearance | Light yellow crystals or powder |
| Melting point | 260–277°Ca |
| Water solubility | ≈3 mg/L |
a. Most references report narrower melting ranges.
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