UNC1999 |
Catalog No.GC11375
One-Click Copy Product Info
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UNC1999 is an orally active inhibitor of EZH2 (IC50=2nM) and EZH1 (IC50=45nM).
Products are for research use only. Not for human use. We do not sell to patients.
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.
| 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 | |
| Chemical Name | 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 | ||
| Formula | C33H43N7O2 | M.Wt | 569.74 |
| Solubility | ≥ 28.5mg/mL in DMSO | Storage | Store at -20° C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)