Home >> SGC 0946
Related Products
SGC 0946 DOT1L inhibitor,highly potent and selective

Catalog No.A4167
Size Price Stock Qty
10mM (in 1mL DMSO)
$80.00
In stock
5mg
$60.00
In stock
10mg
$105.00
In stock
50mg
$420.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

      

Sample solution is provided at 25 µL, 10mM.

Quality Control

Chemical structure

SGC 0946

Biological Activity

Description SGC 0946 is a potent inhibitor of DOT1L methyltransferase with IC50 value of 0.3 nM.
Targets DOT1L          
IC50 0.3 nM          

Protocol

Cell experiment [1]:

Cell lines

Molm13 MLL and A431 cell lines

Preparation method

The solubility of this compound in DMSO is >31 mg/ml. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

0-10 μM

Applications

SGC0946 showed time- and dose-dependent reductions in the H3K79me2 mark in the Molm13 MLL cell line that has the MLL/AF9 translocation. Quantitative assessment of H3K79me2 levels as measured by automated epifluorescence microscopy in MCF10A cells showed a substantially improved DOT1L inhibitory potency of SGC0946 (IC50 8.8±1.6 nM) compared with EPZ004777 (IC50 84±20nM). A similar observation was made in A431 cells, with IC50s of 2.65 nM and 264nM for SGC0946 and EPZ004777, respectively.

References:

[1] Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, Marineau JJ, Qi J, Barsyte-Lovejoy D, Yi J, Marcellus R, Iacob RE, Engen JR, Griffin C, Aman A, Wienholds E, Li F, Pineda J, Estiu G, Shatseva T, Hajian T, Al-Awar R, Dick JE, Vedadi M, Brown PJ, Arrowsmith CH, Bradner JE, Schapira M. Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. Nat Commun. 2012;3:1288.

SGC 0946 Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

SGC 0946 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Chemical Properties

Cas No. 1561178-17-3 SDF Download SDF
Canonical SMILES CC(C)(C)C1=CC=C(NC(NCCCN(C[[email protected]@H]2[[email protected]@H](O)[[email protected]@H](O)[[email protected]](N3C4=NC=NC(N)=C4C(Br)=C3)O2)C(C)C)=O)C=C1
Formula C28H40BrN7O4 M.Wt 618.57
Solubility >31mg/mL in DMSO Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

Background

SGC 0946 is a potent small-molecule inhibitor of protein methyltransferase (PMT) DOT1L, a unique protein lysine methyltransferase (PKMT) catalyzing the methylation of histone H3 on Lysine 79 (H3K79), with the half maximal inhibition concentration IC50 value of 0.3 nM [1].

As a brominated analogue of EPZ004777, SGC 0946 exhibits substantially increased cellular inhibitory potency than its predecessor, where SGC 0946 reduces the methylation of H3K79 in both MCF10A (IC50: 8.8 nM) and A431 (IC50: 2.65 nM) cells compared with EPZ004777 (IC50: 84 nM and 264 nM respectively). This greatly increased cellular inhibitory potency of SGC 0946 can be attributed to lower off-rate and to improved cell permeability [1].

Reference

References:
[1] Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, Marineau JJ, Qi J, Barsyte-Lovejoy D, Yi J, Marcellus R, Iacob RE, Engen JR, Griffin C, Aman A, Wienholds E, Li F, Pineda J, Estiu G, Shatseva T, Hajian T, Al-Awar R, Dick JE, Vedadi M, Brown PJ, Arrowsmith CH, Bradner JE, Schapira M. Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. Nat Commun. 2012;3:1288. doi: 10.1038/ncomms2304.