NSC 663284

NSC 663284 (DA-3003-1) is a potent, cell-permeable, and irreversible Cdc25 dual specificity phosphatase inhibitor, has an IC₅₀ for Cdc25B2 of 0.21 μM. NSC 663284 exhibits mixed competitive kinetics against Cdc25A, Cdc25B(2), and Cdc25C with Ki values of 29, 95, and 89 nM, respectively^[1]. NSC 663284 inhibits NSD2 (IC₅₀ of 170 nM) through a direct interaction with the catalytic SET domain (K_d of 370 nM)^[2]. IC50 & Target: IC50: 0.21 μM (Cdc25B2)^[1] In Vitro: NSC 663284 (3-100μM; 48 hours) has a mean IC₅₀ value in the NCI 60 Cell human tumor panel of 1.5 ± 0.6 μM, has IC₅₀ values of 0.2 μM in human breast cancer MDA-MB-435 and MDA-N cells, has an IC₅₀ value of 1.7 μM in human breast MCF-7 cells in culture^[1].
NSC 663284 has relative IC₅₀ values for Cdc25B2 (IC₅₀=0.21 μM) are 20- and 450-fold lower than for VHR (IC₅₀=4.0 μM) or PTP1B (IC₅₀>4.0 μM), respectively^[1].
In Vivo: NSC 663284 (intravenous injection; 2, 3, and 5mg/kg) inhibits the growth of subcutaneous human colon HT29 xenografts in SCID mice. After a single dose of 5 mg/kg, NSC 663284 is not detectable in plasma or tissues beyond 5 min. Following NSC 663284 treatment of tumor-bearing SCID mice, reduces glutathione concentrations in HT29 tumor are decreased to a greater extent and remained decreased for longer than the reduced glutathione concentrations in liver and kidneys^[3].