3D Mol Similar

UNC 1999

: Iupac 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; CAS No.: 1431612-23-5; Molecular Weight：569.7; Modify Date.: 2022-11-22 20:11; Introduction: 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. View more+

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1. Names and Identifiers

: 1.1 Name; UNC 1999; 1.2 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]- 1-Isopropyl-6-[6-(4-isopropyl-1-piperazinyl)-3-pyridinyl]-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide CS-999 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 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 s7165 UNC 1999 UNC-1999; View all

1.3 CAS No.: 1431612-23-5

1.4 CID: 72551585

1.5 Molecular Formula: C33H43N7O2 (isomer)

1.6 Inchi: 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)

1.7 InChIkey: DPJNKUOXBZSZAI-UHFFFAOYSA-N

1.8 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

1.9 Isomers 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

2. Properties

2.1 Density: 1.23±0.1 g/cm3(Predicted)

2.1 Boiling point: 804.7±65.0 °C(Predicted)

2.1 Refractive index: 1.643

2.1 Flash Point: 440.4±34.3 °C

2.1 Precise Quality: 569.347839

2.1 PSA: 99.41000

2.1 logP: 5.89490

2.1 Solubility: DMSO: soluble15mg/mL, clear

2.2 Appearance: white to beige

2.3 Storage: 2-8°C

2.4 Color/Form: white to beige

2.5 pKa: 11.84±0.10(Predicted)

2.6 Water Solubility: DMSO: soluble15mg/mL, clear

2.7 StorageTemp: 2-8°C

3. Use and Manufacturing

3.1 Usage: 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] UNC 1999Supplier

4. Safety and Handling

4.1 Symbol: GHS07

4.1 Hazard Codes: Xn

4.1 Signal Word: Warning

4.1 Risk Statements: 22

4.1 Safety Statements: 22

4.1 Hazard Declaration: H302

4.1 RIDADR: NONH for all modes of transport

4.1 Caution Statement: P264, P270, P301+P312, P330, P501

4.1 WGK Germany: 3

5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Acute toxicity - Oral, Category 4

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word	Warning
Hazard statement(s)	H302 Harmful if swallowed
Precautionary statement(s)
Prevention	P264 Wash ... thoroughly after handling. P270 Do not eat, drink or smoke when using this product.
Response	P301+P312 IF SWALLOWED: Call a POISON CENTER/doctor/…if you feel unwell. P330 Rinse mouth.
Storage	none
Disposal	P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

View all

6. Other Information

6.0 Target: Value

6.1 EZH2 (Cell-free assay): 2 nM

6.2 EZH1 (Cell-free assay): 45 nM

6.3 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.

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

6.5 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.

6.6 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.

6.7 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]

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

6.9 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; View all

7. Computational chemical data

Molecular Weight: 569.7g/mol
Molecular Formula: C₃₃H₄₃N₇O₂
Compound Is Canonicalized: True
XLogP3-AA: 4.8
Exact Mass: 569.34782364
Monoisotopic Mass: 569.34782364
Complexity: 1030
Rotatable Bond Count: 9
Hydrogen Bond Donor Count: 2
Hydrogen Bond Acceptor Count: 6
Topological Polar Surface Area: 95.4
Heavy Atom Count: 42
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Isotope Atom Count: 0
Covalently-Bonded Unit Count: 1
CACTVS Substructure Key Fingerprint: AAADcfB/sAAAAAAAAAAAAAAAAAAAAWAAAAA8WIEAAAAAAFgB/AAAHgAYAAAADCjBngQ/8PPIEACqAzd3dACShCk1giAZ2KE4ZNiIYPrA3dGUpQhongLIyacciMCOwAACQAASAACAAASAACQAAAAAAAAAAA==

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UNC-1999