WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H407107
CAS#: 1561178-17-3
Description: SGC0946 is a potent and selective inhibitor of DOT1L, which potently and selectively kills cells containing an MLL translocation. SGC0946 inhibits DOT1L with an IC50 of 0.3nM in a radioactive enzyme assay and is over 100-fold selective for other HMTs. In addition, SGC0946 potently reduces H3K79 dimethylation with cellular IC50 of 2.6nM in A431 cells, and 8.8nM in MCF10A cells.
Hodoodo Cat#: H407107
Name: SGC-0946
CAS#: 1561178-17-3
Chemical Formula: C28H40BrN7O4
Exact Mass: 617.23
Molecular Weight: 618.580
Elemental Analysis: C, 54.37; H, 6.52; Br, 12.92; N, 15.85; O, 10.35
Synonym: SGC-0946; SGC 0946; SGC0946.
IUPAC/Chemical Name: 1-(3-((((2R,3S,4R,5R)-5-(4-amino-5-bromo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(isopropyl)amino)propyl)-3-(4-isobutylphenyl)urea
InChi Key: UZLAJVZJBSZSJL-VBHAUSMQSA-N
InChi Code: InChI=1S/C28H40BrN7O4/c1-16(2)12-18-6-8-19(9-7-18)34-28(39)31-10-5-11-35(17(3)4)14-21-23(37)24(38)27(40-21)36-13-20(29)22-25(30)32-15-33-26(22)36/h6-9,13,15-17,21,23-24,27,37-38H,5,10-12,14H2,1-4H3,(H2,30,32,33)(H2,31,34,39)/t21-,23-,24-,27-/m1/s1
SMILES Code: O=C(NC1=CC=C(CC(C)C)C=C1)NCCCN(C[C@H]2O[C@@H](N3C=C(Br)C4=C(N)N=CN=C43)[C@H](O)[C@@H]2O)C(C)C
Appearance: 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: | SGC0946 is a highly potent and selective DOT1L methyltransferase inhibitor with IC50 of 0.3 nM. |
| In vitro activity: | This study next treated MYCN gene–amplified BE(2)-C and Kelly cells with vehicle control or 1.25 μmol/L SGC0946 for 72 hours, 96 hours, or 7 days. Immunoblot analyses confirmed that treatment with SGC0946 led to reduction in H3K79me2 72 hours posttreatment and more significantly 7 days posttreatment (Fig. 4D). RT-PCR analysis showed that SGC0946 reduced the expression of the DOT1L and N-Myc target gene E2F2 (Fig. 4E), and Alamar blue assays confirmed that SGC0946 dose-dependently reduced BE(2)-C and Kelly cells' proliferation (Fig. 4F). In contrast, treatment with SGC0946 did not reduce E2F2 gene expression and did not have an effect on cell proliferation in MYCN gene nonamplified NBL-S and SK-N-FI neuroblastoma cells (Fig. 4G and H). Taken together, the data suggest that DOT1L is required for MYCN-amplified neuroblastoma cell proliferation, and that DOT1L inhibitors are effective anticancer agents against MYCN-amplified neuroblastoma. Reference: Cancer Res. 2017 May 1;77(9):2522-2533. https://cancerres.aacrjournals.org/content/77/9/2522.long |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 55.5 | 89.67 | |
| DMF | 10.0 | 16.17 | |
| Ethanol | 57.3 | 92.61 | |
| Ethanol:PBS (pH 7.2) (1:4) | 0.2 | 0.32 |
The following data is based on the product molecular weight 618.58 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. Wong M, Tee AEL, Milazzo G, Bell JL, Poulos RC, Atmadibrata B, Sun Y, Jing D, Ho N, Ling D, Liu PY, Zhang XD, Hüttelmaier S, Wong JWH, Wang J, Polly P, Perini G, Scarlett CJ, Liu T. The Histone Methyltransferase DOT1L Promotes Neuroblastoma by Regulating Gene Transcription. Cancer Res. 2017 May 1;77(9):2522-2533. doi: 10.1158/0008-5472.CAN-16-1663. Epub 2017 Feb 16. PMID: 28209620. 2. 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. Erratum in: Nat Commun. 2013;4:1893. PMID: 23250418. |
| In vitro protocol: | 1. Wong M, Tee AEL, Milazzo G, Bell JL, Poulos RC, Atmadibrata B, Sun Y, Jing D, Ho N, Ling D, Liu PY, Zhang XD, Hüttelmaier S, Wong JWH, Wang J, Polly P, Perini G, Scarlett CJ, Liu T. The Histone Methyltransferase DOT1L Promotes Neuroblastoma by Regulating Gene Transcription. Cancer Res. 2017 May 1;77(9):2522-2533. doi: 10.1158/0008-5472.CAN-16-1663. Epub 2017 Feb 16. PMID: 28209620. 2. 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. Erratum in: Nat Commun. 2013;4:1893. PMID: 23250418. |
| In vivo protocol: | TBD |
Wenyu Yu, Emma J. Chory, Amy K. Wernimont, Wolfram Tempel, Alex Scopton, Alexander Federation, Jason J. Marineau, Jun Qi, Dalia Barsyte-Lovejoy, Joanna Yi, Richard Marcellus, Roxana E. Iacob, John R. Engen, Erno Wienholds, Fengling Li, Javier Pineda, Guillermina Estiu, Tatiana Shatseva, Taraneh Hajian, Rima Al-awar, John E. Dick, Masoud Vedadi, Peter J. Brown, Cheryl H. Arrowsmith*, James E. Bradner*, Matthieu Schapira*. Nature Communications 3 : 1288doi:10.1038/ncomms2304 (2012)
