UNC1999 是一种有效，选择性和SAM-竞争性的 EZH2 和 EZH1 抑制剂，IC₅₀ 分别为 <10 nM 和 45 nM。

UNC1999 is a SAM-competitive, potent and selective inhibitor of EZH2/1 with IC 50 s of <10 nM and 45 nM, repectively.

Solid

IC50: <10 nM (EZH2), 45 nM (EZH1)

UNC1999, the first orally bioavailable inhibitor that has high in vitro potency for wild-type and mutant EZH2 as well as EZH1, a closely related H3K27 methyltransferase that shares 96% sequence identity with EZH2 in their respective catalytic domains. UNC1999 is highly selective for EZH2 and EZH1 over a broad range of epigenetic and non-epigenetic targets, competitive with the cofactor SAM, and non-competitive with the peptide substrate. UNC1999 has Ki values of 4,700 nM, 65 nM, 300 nM, and 1,500 nM for sigma1, sigma2, histamine H3, and NET, respectively. NC1999 selectively kills DB cells, a DLBCL cell line with the EZH2 Y641N mutation. UNC1999 displays a concentration- and time-dependent inhibition of DB cell proliferation (EC50=633±101 nM (n=3)). has not independently confirmed the acc

A single intraperitoneal (IP) injection of UNC1999 at 15, 50, or 150 mg/kg achieved high C max (9,700-11,800 nM) and exhibited dose linearity in male Swiss albino mice. Both the 150 and 50 mg/kg IP doses resulted in the plasma concentrations of UNC1999 above its cellular IC 50 over the entire 24 h period while the 15 mg/kg IP dose led to the plasma concentrations of UNC1999 above its cellular IC 50 for approximately 12 h. We next examined whether UNC1999 is orally bioavailable and are pleased to find that a single 50 mg/kg oral dose of UNC1999 achieved high C max (4,700 nM) and good exposure levels in male Swiss albino mice. The plasma concentrations of UNC1999 are maintained above its cellular IC 50 for approximately 20 h following this single oral dose. It is worth noting that all doses including the 150 mg/kg IP dose are wel

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Konze KD, et al. An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1. ACS Chem Biol. 2013;8(6):1324-34.

In Vitro: DMSO : 100 mg/mL (175.52 mM; Need ultrasonic)H₂O : < 0.1 mg/mL (ultrasonic;warming;heat to 80°C) (insoluble)配制储备液