Chemistry:AOH1996
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| Formula | C26H22N2O4 |
| Molar mass | 426.472 g·mol−1 |
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AOH1996 is an experimental anticancer medication which acts as a small molecule inhibitor of proliferating cell nuclear antigen (PCNA) and is in Phase I clinical trials at City of Hope as of August 2023 for the treatment of solid tumors.[1][2][3][4]
AOH1996 was created to target a post-translationally modified isoform of PCNA, termed caPCNA, which is preferentially found in cancer cells. PCNA is crucial in the body for DNA repair, but targeting it is difficult because of its role in healthy cells. By selectively targeting caPCNA, it may be possible to kill cancer cells without affecting healthy tissues.[5] In vitro testing demonstrated that AOH1996 inhibited the growth and induced cell cycle arrest and apoptotic cell death in a wide variety of cancer cell lines, but had no effect on several normal, nonmalignant cell types.[6][7] In mouse and dog animal models, there were no observed side effects or toxicity even at six times the effective dose.[3] It could be used either as a monotherapy (single drug regimen) or in combination with one or more other chemotherapy drugs.
Although the press described it as a "miracle drug" that would cure cancer, some experts have expressed skepticism. Prof Dorothy Bennett, Director of the Molecular and Clinical Sciences Research Institute, St George’s, University of London, critiqued the paper's cancer killing claim as actually a modest slowing of growth.[8]
The substance was named after the initials and the birth year of Anna Olivia Healey, who died of neuroblastoma in 2006. The funds collected by her parents have helped support the development of the chemical compound.[6][9]
References
- ↑ Malkas LH, Horne D, Hickey RJ, Gu L, "PCNA Inhibitors", WO patent 2017049206, published 2017-03-23, assigned to City Of Hope
- ↑ "Arginine shortage induces replication stress and confers genotoxic resistance by inhibiting histone H4 translation and promoting PCNA ubiquitination". Cell Reports 42 (4): 112296. March 2023. doi:10.1016/j.celrep.2023.112296. PMID 36961817.
- ↑ 3.0 3.1 "Small molecule targeting of transcription-replication conflict for selective chemotherapy". Cell Chemical Biology 30 (10): 1235–1247.e6. July 2023. doi:10.1016/j.chembiol.2023.07.001. PMID 37531956.
- ↑ "AOH1996 for the Treatment of Refractory Solid Tumors". United States National Library of Medicine. 2023-08-18. https://clinicaltrials.gov/study/NCT05227326.
- ↑ "The Anticancer Activity of a First-in-class Small-molecule Targeting PCNA". Clinical Cancer Research 24 (23): 6053–6065. December 2018. doi:10.1158/1078-0432.CCR-18-0592. PMID 29967249.
- ↑ 6.0 6.1 "Anna (9) starb an Krebs – jetzt ist die Wunderpille nach ihr benannt" (in de). 20 Minuten. 2023-08-02. https://www.20min.ch/story/anna-9-starb-an-krebs-jetzt-ist-die-wunderpille-nach-ihr-benannt-589469551365.
- ↑ "'Cancer-killing pill' that appears to 'annihilate' solid tumours is now being tested on humans" (in en). 2023-08-02. https://news.sky.com/story/cancer-killing-pill-that-appears-to-annihilate-solid-tumours-is-now-being-tested-on-humans-12932133.
- ↑ "expert reaction to study on use of small molecule ligand AOH1996 for inhibiting tumour growth in animals". Science Media Center. 2023-08-02. https://www.sciencemediacentre.org/expert-reaction-to-study-on-use-of-small-molecule-ligand-aoh1996-for-inhibiting-tumour-growth-in-animals/.
- ↑ "AOH-1996 Is Here!". ANNA Fund. 2021-12-21. https://annafund.com/2021/12/23/aoh-1996-is-here/.
External links
- "A New Mode of Cancer Treatment". 2 August 2023. https://www.science.org/content/blog-post/new-mode-cancer-treatment.
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