WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406228
CAS#: 1346574-57-9
Description: GSK126, also known as GSK2816126 is a potent, highly selective, S-adenosyl-methionine-competitive, small-molecule inhibitor of EZH2 methyltransferase activity. GSK126 decreases global H3K27me3 levels and reactivates silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and markedly inhibits the growth of EZH2 mutant DLBCL xenografts in mice. Together, these data demonstrate that pharmacological inhibition of EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma.
Hodoodo Cat#: H406228
Name: GSK126
CAS#: 1346574-57-9
Chemical Formula: C31H38N6O2
Exact Mass: 526.31
Molecular Weight: 526.670
Elemental Analysis: C, 70.70; H, 7.27; N, 15.96; O, 6.08
Synonym: GSK2816126; GSK-2816126; GSK 2816126; GSK-126; GSK126; GSK-126.
IUPAC/Chemical Name: (S)-1-(sec-butyl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxamide
InChi Key: FKSFKBQGSFSOSM-QFIPXVFZSA-N
InChi Code: InChI=1S/C31H38N6O2/c1-6-22(5)37-18-20(3)29-25(30(38)34-17-26-19(2)13-21(4)35-31(26)39)14-24(15-27(29)37)23-7-8-28(33-16-23)36-11-9-32-10-12-36/h7-8,13-16,18,22,32H,6,9-12,17H2,1-5H3,(H,34,38)(H,35,39)/t22-/m0/s1
SMILES Code: O=C(C1=CC(C2=CC=C(N3CCNCC3)N=C2)=CC4=C1C(C)=CN4[C@@H](C)CC)NCC5=C(C)C=C(C)NC5=O
Appearance: Off-white to light pink 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
More Info:
Biological target: | GSK126 (GSK2816126A) is a potent, highly selective inhibitor of EZH2 methyltransferase with an IC50 of 9.9 nM. |
In vitro activity: | GSK126 potently inhibits both wild-type and mutant EZH2 methyltransferase activity with similar potencies (Ki=0.5-3 nM) independent of substrate used, and is competitive with S-adenosyl-methionine (SAM) and non-competitive with peptide substrates. GSK126 is highly selective against other methyltransferases and multiple other protein classes (EZH1, IC50=680 nM). Reference: Nature. 2012 Dec 6;492(7427):108-12. https://www.nature.com/articles/nature11606 |
In vivo activity: | GSK126 is administered intraperitoneally at a dose volume of 0.2 mL per 20 g body weight in female beige SCID mice. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and markedly inhibits the growth of EZH2 mutant DLBCL xenografts in mice. Reference: Nature. 2012 Dec 6;492(7427):108-12. https://www.nature.com/articles/nature11606 |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
Soluble in DMSO, not in water | 10.0 | 18.99 | |
Ethanol | 10.0 | 18.99 |
The following data is based on the product molecular weight 526.67 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. McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS, Liu Y, Graves AP, Della Pietra A 3rd, Diaz E, LaFrance LV, Mellinger M, Duquenne C, Tian X, Kruger RG, McHugh CF, Brandt M, Miller WH, Dhanak D, Verma SK, Tummino PJ, Creasy CL. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 2012 Dec 6;492(7427):108-12. doi: 10.1038/nature11606. Epub 2012 Oct 10. PMID: 23051747. 2. Sato T, Kaneda A, Tsuji S, Isagawa T, Yamamoto S, Fujita T, Yamanaka R, Tanaka Y, Nukiwa T, Marquez VE, Ishikawa Y, Ichinose M, Aburatani H. PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer. Sci Rep. 2013;3:1911. doi: 10.1038/srep01911. PMID: 23714854; PMCID: PMC3665955. 3. McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS, Liu Y, Graves AP, Della Pietra A 3rd, Diaz E, LaFrance LV, Mellinger M, Duquenne C, Tian X, Kruger RG, McHugh CF, Brandt M, Miller WH, Dhanak D, Verma SK, Tummino PJ, Creasy CL. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 2012 Dec 6;492(7427):108-12. doi: 10.1038/nature11606. Epub 2012 Oct 10. PMID: 23051747. |
In vitro protocol: | 1. McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS, Liu Y, Graves AP, Della Pietra A 3rd, Diaz E, LaFrance LV, Mellinger M, Duquenne C, Tian X, Kruger RG, McHugh CF, Brandt M, Miller WH, Dhanak D, Verma SK, Tummino PJ, Creasy CL. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 2012 Dec 6;492(7427):108-12. doi: 10.1038/nature11606. Epub 2012 Oct 10. PMID: 23051747. 2. Sato T, Kaneda A, Tsuji S, Isagawa T, Yamamoto S, Fujita T, Yamanaka R, Tanaka Y, Nukiwa T, Marquez VE, Ishikawa Y, Ichinose M, Aburatani H. PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer. Sci Rep. 2013;3:1911. doi: 10.1038/srep01911. PMID: 23714854; PMCID: PMC3665955. |
In vivo protocol: | 1. McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS, Liu Y, Graves AP, Della Pietra A 3rd, Diaz E, LaFrance LV, Mellinger M, Duquenne C, Tian X, Kruger RG, McHugh CF, Brandt M, Miller WH, Dhanak D, Verma SK, Tummino PJ, Creasy CL. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 2012 Dec 6;492(7427):108-12. doi: 10.1038/nature11606. Epub 2012 Oct 10. PMID: 23051747. |
1: McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS, Liu Y, Graves AP, Della Pietra A 3rd, Diaz E, LaFrance LV, Mellinger M, Duquenne C, Tian X, Kruger RG, McHugh CF, Brandt M, Miller WH, Dhanak D, Verma SK, Tummino PJ, Creasy CL. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 2012 Dec 6;492(7427):108-12. doi: 10.1038/nature11606. Epub 2012 Oct 10. PubMed PMID: 23051747.
Mazzi S, Dessen P, Vieira M, Dufour V, Cambot M, El-Khoury M, Antony-Debre I, Arkoun B, Basso-Valentina F, Ben Abdelouahab S, Edmond V, Rameau P, Petermann R, Wittner M, Cassinat B, Plo I, Debili N, Raslova H, Vainchenker W. Dual role of EZH2 on megakaryocyte differentiation. Blood. 2021 Jun 11:blood.2019004638. doi: 10.1182/blood.2019004638. Epub ahead of print. PMID: 34115825.