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PLoS Med 3:e420 Singh RK, van Haandel L, Kiptoo P, Becker ML, Siahaan TJ, Funk RS (2019) Methotrexate disposition, anti-folate activity and efficacy in the collagen-induced arthritis mouse model
DNA methyltransferase inhibitors and other epigenetic therapies are being explored to reverse these methylation changes and enhance therapeutic efficacy

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Particularly the heterodimer XPF-ERCC1, a rate-limiting factor for the NER pathway, that has single-strand DNA endonuclease activity and incises DNA on the 5 side of cisplatin adducts, and also participate in the repair of double-strand breaks induced by ICLs 11

Peters J, Kalivas PW
The clinical translation is further hampered by unclear pharmacokinetics and delivery hurdles, including poorly characterized in vivo metabolic fate, bioavailability, and optimal dosage windows, coupled with a lack of advanced formulation strategies for efficient and targeted delivery
