SGC 0946

A potent inhibitor of DOT1L

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库存: 现货

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数量
1mg

￥462.00

370.00

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5mg

￥1087.00

870.00

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10mg

￥1700.00

1360.00

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25mg

￥3425.00

2740.00

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50mg

￥6337.00

5070.00

- +

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货号: ajci7224
CAS: 1561178-17-3
别名:
分子式: C28H40BrN7O4
分子量: 618.57
纯度: >98%
溶解度: ≥ 30.95 mg/mL in DMSO, ≥ 97.6 mg/mL in EtOH with ultrasonic
储存: Store at -20°C
库存: 现货

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

参考文献:
[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.

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.
参考文献: [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.