The anti-cancer drug is a small molecule that was designed to interfere with the scaffolding molecule PCNA which clamps dna to allow replication tools to attach it was found that PCNA in cancer cells is actually an isomer, allowing specific targeting pubmed.ncbi.nlm.nih.gov/17159154/
furthermore the isomer doesn’t seem to be the result of radom mutation but rather a mistranslation, which seems to be universal among many cancers — making evolutionary resistance unlikely.
The woman working on this started 20 years ago, and in the process found the caPCNA isomer. They first tried targeting with antibodies, too big to disperse into solid tumors. Then developed a small molecule that worked in vitro but had an in vivo bio half-life of 30 minutes.
Then they developed a long-half-life molecule that does the same thing, rotating the diaryl ether and added another ether — the subject of this paper
The drug appears to work as a broad-spectrum chemotherapy sensitizer too, making simple chemotherapies like cisplatin substantially more destructive towards solid tumors
