Basic information Description Features In vitro In vivo Safety Supplier Related
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UNC 1999

Basic information Description Features In vitro In vivo Safety Supplier Related

UNC 1999 Basic information

Product Name:
UNC 1999
Synonyms:
  • 1H-Indazole-4-carboxamide, N-[(1,2-dihydro-6-methyl-2-oxo-4-propyl-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[6-[4-(1-methylethyl)-1-piperazinyl]-3-pyridinyl]-
  • N-[(1,2-Dihydro-6-methyl-2-oxo-4-propyl-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[6-[4-(1-methylethyl)-1-piperazinyl]-3-pyridinyl]-1H-indazole-4-carboxamide UNC1999
  • UNC 1999
  • UNC1999
  • UNC-1999
  • N-[(1,2-Dihydro-6-Methyl-2-oxo-4-propyl-3-pyridinyl)Methyl]-1-(1-Methylethyl)-6-[6-[4-(1-Methylethyl)-1-piperazinyl]-3-pyridinyl]-1H-indazole-4-carboxaMide
  • CS-999
  • UNC1999; UNC 1999
CAS:
1431612-23-5
MF:
C33H43N7O2
MW:
569.74
Product Categories:
  • Inhibitors
  • API
Mol File:
1431612-23-5.mol
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UNC 1999 Chemical Properties

Boiling point:
804.7±65.0 °C(Predicted)
Density 
1.23±0.1 g/cm3(Predicted)
storage temp. 
2-8°C
solubility 
DMSO: soluble15mg/mL, clear
pka
11.84±0.10(Predicted)
form 
powder
color 
white to beige
Stability:
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
InChIKey
DPJNKUOXBZSZAI-UHFFFAOYSA-N
CAS DataBase Reference
1431612-23-5
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Safety Information

Hazard Codes 
Xn
Risk Statements 
22
WGK Germany 
3
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UNC 1999 Usage And Synthesis

Description

UNC1999 is a potent, orally bioavailable and selective inhibitor of EZH2 and EZH1 with IC50 of 2 nM and 45 nM in cell-free assays, respectively, showing >1000-fold selectivity over a broad range of epigenetic and non-epigenetic targets.

Features

The first orally bioavailable inhibitor against wild-type and mutant EZH2 as well as EZH1.

In vitro

UNC1999 is highly potent for both EZH2 Y641N and EZH2 Y641F mutants in vitro. UNC1999 causes concentration-dependent reductions of H3K27me3 in MCF10A cells with IC50 of 124 nM , while shows low cellular toxicity. UNC1999 displays potent, concentration-dependent inhibition of cell proliferation with EC50 of 633 nM in a DLBCL cell line harboring the EZH2Y641N mutant. In addition, biotinylated UNC1999 enriches EZH2 from HEK293T cell lysates, and thus may be used in chemoproteomics studies.

In vivo

Treatment of UNC1999 (150 and 50 mg/kg, i.p.) results in the plasma concentrations of UNC1999 above its cellular IC50 over 24 hours in vivo. In addition, UNC1999 is also orally bioavailable in mice, which makes chronic animal studies more practical and convenient.

Description

UNC1999 (1431612-23-5) is an orally bioavailable, highly selective inhibitor of both wild-type and mutant EZH1 and EZH2 lysine methyltransferases (IC50‘s = 45 nM and 2 nM respectively).1?Inhibition of EZH2 with UNC1999 enhanced the efficacy of gefitinib (Cat.# 10-1148) in suppressing the proliferation of colon cancer cells

Uses

The histone H3 lysine 27 (H3K27) methyltransferase EZH2 plays an important role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. UNC1999 is a cell-permeable EZH2 inhibitor (IC50 = 2 nM) that is 22-fold selective over EZH1 and >1,000-fold selective over other histone methytranferases. UNC1999 has been shown to inhibit H3K27 methylation in MCF10A cells with an IC50 value of 124 nM.[Cayman Chemical]

Uses

UNC1999 acts as an inhibitor for lysine methyltransferases EZH2 and EZH1 which have been implicated in the expression of various cancers.

Biochem/physiol Actions

The polycomb repressive complex 2 (PRC2), which represses gene expression through methylation of histone H3 on lysine 27 (H3K27), contains either EZH1 or EZH2 as its catalytic subunit, with EZH1 being found in both dividing and non-dividing cells, whereas EZH2 is only found in actively dividing cells. UNC1999 is an orally bioavaliable selective inhibitor of both EZH2 and EZH1 lysine methyltransferases with IC50 < 10 nM for EZH2 and 45 nM for EZH1. UNC1999 potently inhibited both wild-type and mutant Y641N EZH2 methyltransferase activity with less than a 5-fold difference in potency, and selectively killed diffused large B cell lymphoma (DLBCL) cells bearing Y641 point mutations. It was selective for EZH2 and EZH1 over 15 other lysine, arginine and DNA methyltransferases. UNC1999 is competitive with the cofactor S-adenosylmethionine (SAM) and non-competitive with the peptide substrate. Because it inhibits both EZH2 and EZH1, UNC1999 has potential advantages over EZH2 selective inhibitors in the disease settings where both PRC2 – EZH2 and PRC2 – EZH1 contribute to the methylation of H3K27. For full characterization details, please visit the UNC1999 probe summary on the Structural Genomics Consortium (SGC) website.UNC2400 is the negative control for the active probe, UNC1999. To request a sample of the negative control from the SGC, click here.To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc

storage

Store at +4°C

References

1) Konze?et al. (2013),?An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1; ACS Chem. Biol.,?8?1324 2) Katona?et al. (2014),?EZH2 inhibition enhances the efficacy of an EGFR inhibitor in suppressing colon cancer cells; Cancer Biol. Ther.,?15?1677

UNC 1999Supplier

Shanghai Boyle Chemical Co., Ltd.
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Email
sales@boylechem.com
Products Intro
Product Name:UNC1999
CAS:1431612-23-5
J & K SCIENTIFIC LTD.
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010-82848833 400-666-7788
Email
jkinfo@jkchemical.com
Products Intro
Product Name:UNC1999
CAS:1431612-23-5
Package:25Mg,5Mg
Dalian Meilun Biotech Co., Ltd.
Tel
0411-62910999 13889544652
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meilunui@163.com
Products Intro
Product Name:UNC 1999
CAS:1431612-23-5
Purity:>98%,BR Package:5MG;25MG; Remarks:MB3194
Haoyuan Chemexpress Co., Ltd.
Tel
021-58950125
Email
info@chemexpress.com
Products Intro
Product Name:UNC1999
CAS:1431612-23-5
Purity:>98% Package:714RMB/5mg
UHN Shanghai Research & Development Co., Ltd.
Tel
021-58958002 18930822973
Email
SALES@UHNSHANGHAI.COM
Products Intro
Product Name:UNC1999
CAS:1431612-23-5
Purity:98% LC-MS Package:10g, 50g, 100g, 1Kg Remarks:B100831