Target: MYC
Kd value: 6.5 ± 1.0 nM
KJ Pyr 9 is a novel small molecule inhibitor of MYC, with the Kd value of 6.5 ± 1.0 nM. Besides, KJ Pyr 9 also suppresses the formation of MYC-MAX and oncogenic transformation induced by MYC in cell culture [1].
In Vitro: In chicken embryo fibroblasts, KJ Pyr 9 was found to have the ability to interfere with the oncogenic activity of MYC, with the best aqueous solubility. Besides, in human B-cell line P493-6, 20 μM KJ Pyr 9 could significantly inhibit cell proliferation, and KJ Pyr 9 could also inhibit the proliferation of NCI-H460, MDA-MB-231, and SUM-159PT cell lines, with the IC50 values between 5-10 μM. Furthermore, treatment of P493-6 cells with KJ Pyr 9 could significantly suppress the transcription ability of MYC [1].
In Vivo: KJ Pyr 9 was found to have no acute toxicity in mouse and rat at a dose of 10 mg/kg, with an impressive ability to cross the blood-brain barrier. Besides, in a MDA-MB-231 cells xenograft tumor nude mice model, intraperitoneal injection with 10 mg/kg KJ Pyr 9 for 31 days could significantly inhibit tumor growth, while having no effect on the body weight [1].
Clinical trial: No data available recently.
Reference:
[1] Hart J R, Garner A L, Yu J, et al. Inhibitor of MYC identified in a Kröhnke pyridine library[J]. Proceedings of the National Academy of Sciences, 2014, 111(34): 12556-12561.