WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406266
Description: UNC1999, the first orally bioavailable inhibitor that has high in vitro potency for wildtype and mutant EZH2 as well as EZH1. UNC1999 was 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 was orally bioavailable in mice, making this inhibitor a valuable tool for investigating the role of EZH2 and EZH1 in chronic animal studies. UNC-1999 represents a useful tools for the biomedical community to investigate the role of EZH2 and EZH1 in health and disease.
MedKoo Cat#: 406266
Chemical Formula: C33H43N7O2
Exact Mass: 569.34782
Molecular Weight: 569.74022
Elemental Analysis: C, 69.57; H, 7.61; N, 17.21; O, 5.62
Synonym: UNC1999; UNC 1999; UNC-1999;
IUPAC/Chemical Name: 1-isopropyl-6-(6-(4-isopropylpiperazin-1-yl)pyridin-3-yl)-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide
InChi Key: DPJNKUOXBZSZAI-UHFFFAOYSA-N
InChi Code: InChI=1S/C33H43N7O2/c1-7-8-24-15-23(6)37-33(42)28(24)19-35-32(41)27-16-26(17-30-29(27)20-36-40(30)22(4)5)25-9-10-31(34-18-25)39-13-11-38(12-14-39)21(2)3/h9-10,15-18,20-22H,7-8,11-14,19H2,1-6H3,(H,35,41)(H,37,42)
SMILES Code: O=C(NCC1=C(CCC)C=C(C)NC1=O)C2=C3C(N(C(C)C)N=C3)=CC(C4=CC=C(N5CCN(C(C)C)CC5)N=C4)=C2
Appearance: White solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||UNC1999 is an inhibitor of EZH2/1 with IC50s of <10 nM and 45 nM, repectively.|
|In vitro activity:||The MTT, apoptosis, wound-healing and cell migration assays were used to investigate the effects of the EZH2 inhibitor UNC1999 on the proliferation and migration of bladder cancer cell lines E-J and 5637 (cells in the control groups were treated with an equal volume of DMSO; Fig. 2). The MTT assay revealed that treatment with UNC1999 inhibited the proliferation of the bladder cancer cell lines in a dose- and time-dependent manner (Fig. 2A and B). UNC1999 exhibited the greatest inhibitory effect at a final concentration of 100 µM and an incubation period of 72 and 120 h. Apoptosis analysis revealed that UNC1999 induced significant apoptosis in E-J and 5637 cells (Fig. 2C-E). Reference: Oncol Lett. 2019 Jul;18(1):907-915. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539677/|
|In vivo activity:||To explore the antitumor activity of UNC1999 in vivo, E-J tumor xenografts were analyzed. UNC1999 exhibited significant antitumor activity in nude mice bearing E-J tumor xenografts at a dose of 50 mg/kg (P<0.05; Fig. 4A). In order to examine the mechanism underlying the inhibition of tumor growth by UNC1999 in vivo, the expression levels of JAK2 and STAT3 were measured using western blotting. The expression levels of JAK2 and STAT3 were significantly decreased in the tumors treated with UNC1999 compared with the control tumors (P<0.05; Fig. 4B-E). These results suggested that UNC1999 inhibited tumor growth in vivo by inhibiting EZH2 and subsequent inhibition of the JAK2/STAT3 signaling pathway. Reference: Oncol Lett. 2019 Jul;18(1):907-915. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539677/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
|1 M HCl||56.97||99.99|
The following data is based on the product molecular weight 569.74022 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|Formulation protocol:||1. Chen Z, Du Y, Liu X, Chen H, Weng X, Guo J, Wang M, Wang X, Wang L. EZH2 inhibition suppresses bladder cancer cell growth and metastasis via the JAK2/STAT3 signaling pathway. Oncol Lett. 2019 Jul;18(1):907-915. doi: 10.3892/ol.2019.10359. Epub 2019 May 14. PMID: 31289569; PMCID: PMC6539677.|
|In vitro protocol:||1. Chen Z, Du Y, Liu X, Chen H, Weng X, Guo J, Wang M, Wang X, Wang L. EZH2 inhibition suppresses bladder cancer cell growth and metastasis via the JAK2/STAT3 signaling pathway. Oncol Lett. 2019 Jul;18(1):907-915. doi: 10.3892/ol.2019.10359. Epub 2019 May 14. PMID: 31289569; PMCID: PMC6539677.|
|In vivo protocol:||1. Chen Z, Du Y, Liu X, Chen H, Weng X, Guo J, Wang M, Wang X, Wang L. EZH2 inhibition suppresses bladder cancer cell growth and metastasis via the JAK2/STAT3 signaling pathway. Oncol Lett. 2019 Jul;18(1):907-915. doi: 10.3892/ol.2019.10359. Epub 2019 May 14. PMID: 31289569; PMCID: PMC6539677.|
1: Zhang P, de Gooijer MC, Buil LC, Beijnen JH, Li G, van Tellingen O. ABCB1 and ABCG2 restrict the brain penetration of a panel of novel EZH2-Inhibitors. Int J Cancer. 2015 Oct 15;137(8):2007-18. doi: 10.1002/ijc.29566. Epub 2015 Apr 24. PubMed PMID: 25868794.
2: Katona BW, Liu Y, Ma A, Jin J, Hua X. EZH2 inhibition enhances the efficacy of an EGFR inhibitor in suppressing colon cancer cells. Cancer Biol Ther. 2014;15(12):1677-87. doi: 10.4161/15384047.2014.972776. PubMed PMID: 25535899.
3: Xu B, On DM, Ma A, Parton T, Konze KD, Pattenden SG, Allison DF, Cai L, Rockowitz S, Liu S, Liu Y, Li F, Vedadi M, Frye SV, Garcia BA, Zheng D, Jin J, Wang GG. Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia. Blood. 2015 Jan 8;125(2):346-57. doi: 10.1182/blood-2014-06-581082. Epub 2014 Nov 13. PubMed PMID: 25395428; PubMed Central PMCID: PMC4287641.
4: Konze KD, Ma A, Li F, Barsyte-Lovejoy D, Parton T, Macnevin CJ, Liu F, Gao C, Huang XP, Kuznetsova E, Rougie M, Jiang A, Pattenden SG, Norris JL, James LI, Roth BL, Brown PJ, Frye SV, Arrowsmith CH, Hahn KM, Wang GG, Vedadi M, Jin J. An orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and EZH1. ACS Chem Biol. 2013;8(6):1324-34. doi: 10.1021/cb400133j. Epub 2013 Apr 24. PubMed PMID: 23614352; PubMed Central PMCID: PMC3773059.