UNC1999
目录号 : GC11375
UNC1999是一种口服活性的EZH2（IC50=2nM）和EZH1（IC50=45nM）抑制剂。
Cas No.:1431612-23-5
Sample solution is provided at 25 µL, 10mM.
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UNC1999 is an orally active inhibitor of EZH2 (IC50=2nM) and EZH1 (IC50=45nM)[1-2]. UNC1999 can be used to investigate the mechanisms of EZH2 and EZH1 in gene expression regulation, cancer development, and stem cell maintenance[3-4].
In vitro, treatment of human colorectal cancer cells (HCT116, LoVo, HCT-15, DLD-1) with UNC1999 (2.5–5μM) for 24–72 hours induces autophagy by upregulating LC3B gene expression transcriptionally, activates endoplasmic reticulum (ER) stress and the PERK/eIF2α pathway of the unfolded protein response (UPR), ultimately promoting tumor cell death[5]. UNC1999 (0.1–100μM) treatment of human bladder cancer cell lines E-J and 5637 for 24–120 hours, UNC1999 significantly inhibits cell proliferation and migration while inducing apoptosis by suppressing EZH2 activity and blocking the JAK2/STAT3 signaling pathway[6].
In vivo, intraperitoneal injection of UNC1999 (15–25mg/kg) twice weekly for 3 weeks in NOG mice bearing MM.1S human multiple myeloma xenografts significantly inhibits tumor growth and prolongs survival[7]. Intraperitoneal injection of UNC1999 (25mg/kg) twice weekly for 4 weeks in BALB/c nude mice inoculated with Y79 human retinoblastoma cells significantly suppresses the growth of subcutaneous xenograft tumors[8].
References:
[1] Zhou C, He A, Kang Q, et al. Development of a UPLC-MS/MS method for determination of a dual EZH1/2 inhibitor UNC1999 in rat plasma. Bioanalysis. 2022 Jan;14(2):67-74.
[2] Xu B, On DM, Ma A, et al. Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia. Blood. 2015 Jan 8;125(2):346-57.
[3] Shinno Y, Takenobu H, Sugino RP, et al. Polycomb EZH1 regulates cell cycle/5-fluorouracil sensitivity of neuroblastoma cells in concert with MYCN. Cancer Sci. 2022 Dec;113(12):4193-4206.
[4] Zhang Q, Deng X, Tang X, et al. MicroRNA-20a Suppresses Tumor Proliferation and Metastasis in Hepatocellular Carcinoma by Directly Targeting EZH1. Front Oncol. 2021 Dec 16;11:737986.
[5] Hsieh YY, Lo HL, Yang PM. EZH2 inhibitors transcriptionally upregulate cytotoxic autophagy and cytoprotective unfolded protein response in human colorectal cancer cells. Am J Cancer Res. 2016 Aug 1;6(8):1661-80.
[6] Chen Z, Du Y, Liu X, et al. EZH2 inhibition suppresses bladder cancer cell growth and metastasis via the JAK2/STAT3 signaling pathway. Oncol Lett. 2019 Jul;18(1):907-915.
[7] Rizq O, Mimura N, Oshima M, et al. Dual Inhibition of EZH2 and EZH1 Sensitizes PRC2-Dependent Tumors to Proteasome Inhibition. Clin Cancer Res. 2017 Aug 15;23(16):4817-4830. doi: 10.1158/1078-0432.CCR-16-2735.
[8] Zhao Y, Cheng Y, Qu Y. The role of EZH2 as a potential therapeutic target in retinoblastoma. Exp Eye Res. 2023 Feb;227:109389.
UNC1999是一种口服活性的EZH2（IC50=2nM）和EZH1（IC50=45nM）抑制剂[1-2]。UNC1999可用于研究EZH2和EZH1在基因表达调控、癌症发生发展以及干细胞维持中的作用机制[3-4]。
在体外，UNC1999（2.5–5μM）处理人结直肠癌细胞（HCT116, LoVo, HCT-15, DLD-1）24–72小时，UNC1999通过转录上调LC3B基因表达诱导细胞自噬，并激活内质网应激（ER stress）及未折叠蛋白反应（UPR）的PERK/eIF2α通路，最终促进肿瘤细胞死亡[5]。UNC1999（0.1–100μM）处理人膀胱癌细胞系E-J和5637 24–120小时，UNC1999通过抑制EZH2活性并阻断JAK2/STAT3信号通路，显著抑制细胞增殖和迁移、诱导细胞凋亡[6]。
在体内，UNC1999（15–25mg/kg）每周2次腹腔注射，用于处理携带MM.1S人多发性骨髓瘤异种移植瘤的NOG小鼠，持续3周，显著抑制了肿瘤生长并延长了小鼠生存期[7]。UNC1999（25mg/kg）每周两次腹腔注射，用于处理接种了Y79人视网膜母细胞瘤细胞的BALB/c裸鼠，持续4周，UNC1999显著抑制了皮下移植瘤的生长[8]。
| Cell experiment [1]: | |
Cell lines | E-J and 5637 cells (human bladder cancer cell lines) |
Preparation Method | E-J and 5637 cells were maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum (FBS) at 37°C, 5% CO₂. Cells were treated with the EZH2 inhibitor UNC1999 at concentrations of 0.1, 1, 10, and 100µM for 24, 72, and 120 hours. |
Reaction Conditions | 0.1-100µM; 24-120h |
Applications | UNC1999 significantly inhibited the proliferation of bladder cancer cells in a dose- and time-dependent manner. UNC1999 induced significant apoptosis and suppressed cell migration and invasion. Mechanistically, UNC1999 reduced the phosphorylation levels of JAK2 and STAT3, indicating inhibition of the JAK2/STAT3 signaling pathway. |
| Animal experiment [2]: | |
Animal models | BALB/c nude mice |
Preparation Method | Y79 retinoblastoma cells were subcutaneously injected into the posterior flank of female BALB/c nude mice. After one week of tumor growth, mice were randomly divided into two groups. One group was treated with UNC1999 (25mg/kg, i.p.) twice a week for 3 weeks. The control group received intraperitoneal injections of vehicle (5% DMSO in corn oil). Tumor volume was measured three times per week. Mice were sacrificed after 4 weeks, and tumors were collected for further analysis. |
Dosage form | 25mg/kg; i.p.; Twice per week for 3 weeks |
Applications | UNC1999 administration significantly inhibited the growth of retinoblastoma xenograft tumors in vivo compared to the vehicle control. UNC1999 treatment reduced the protein levels of EZH2 and phosphorylated STAT3 (pY-STAT3) while increasing the expression of FoxO1 in the excised tumors. |
References: | |
| Cas No. | 1431612-23-5 | SDF | |
| 化学名 | N-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]-1-propan-2-yl-6-[6-(4-propan-2-ylpiperazin-1-yl)pyridin-3-yl]indazole-4-carboxamide | ||
| Canonical SMILES | CCCC1=C(C(=O)NC(=C1)C)CNC(=O)C2=C3C=NN(C3=CC(=C2)C4=CN=C(C=C4)N5CCN(CC5)C(C)C)C(C)C | ||
| 分子式 | C33H43N7O2 | 分子量 | 569.74 |
| 溶解度 | ≥ 28.5mg/mL in DMSO | 储存条件 | Store at -20° C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7552 mL | 8.7759 mL | 17.5519 mL |
| 5 mM | 351 μL | 1.7552 mL | 3.5104 mL |
| 10 mM | 175.5 μL | 877.6 μL | 1.7552 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >99.50%
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