UNC1999 is a SAM-competitive, potent and selective inhibitor ofEZH2/1withIC₅₀s of<10 nM and 45 nM, repectively.

IC50:<10 nm (ezh2), 45 (ezh1)^[1]

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 K_ivalues 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))^[1].

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 IC₅₀over the entire 24 h period while the 15 mg/kg IP dose led to the plasma concentrations of UNC1999 above its cellular IC₅₀for 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 IC₅₀for approximately 20 h following this single oral dose. It is worth noting that all doses including the 150 mg/kg IP dose are well tolerated by all test mice, and no adverse effects are observed^[1].

569.74

Solid

C₃₃H₄₃N₇O₂

1431612-23-5

Room temperature in continental US; may vary elsewhere.

DMSO : 100 mg/mL(175.52 mM;Need ultrasonic)

H₂O :< 0.1 mg/mL (ultrasonic;warming;heat to 80℃)(insoluble)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.25 mg/mL (3.95 mM); Clear solution

  此方案可获得 ≥ 2.25 mg/mL (3.95 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 22.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: 2.25 mg/mL (3.95 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.25 mg/mL (3.95 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 22.5 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: 2.25 mg/mL (3.95 mM); Clear solution; Need warming

  此方案可获得 2.25 mg/mL (3.95 mM) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 22.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。