WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406572
CAS#: 1374601-40-7
Description: BRD4770 is a novel histone methyltransferase inhibitor. BRD4770 reduced cellular levels of di- and trimethylated H3K9 without inducing apoptosis, induced senescence, and inhibited both anchorage-dependent and -independent proliferation in the pancreatic cancer cell line PANC-1. ATM-pathway activation, caused by either genetic or small-molecule inhibition of G9a, may mediate BRD4770-induced cell senescence. BRD4770 may be a useful tool to study G9a and its role in senescence and cancer cell biology.
Hodoodo Cat#: H406572
Name: BRD4770
CAS#: 1374601-40-7
Chemical Formula: C25H23N3O3
Exact Mass: 413.17
Molecular Weight: 413.470
Elemental Analysis: C, 72.62; H, 5.61; N, 10.16; O, 11.61
Synonym: BRD4770; BRD-4770; BRD 4770.
IUPAC/Chemical Name: methyl 2-benzamido-1-(3-phenylpropyl)-1H-benzo[d]imidazole-5-carboxylate
InChi Key: UCGWYCMPZXDHNR-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H23N3O3/c1-31-24(30)20-14-15-22-21(17-20)26-25(27-23(29)19-12-6-3-7-13-19)28(22)16-8-11-18-9-4-2-5-10-18/h2-7,9-10,12-15,17H,8,11,16H2,1H3,(H,26,27,29)
SMILES Code: O=C(C1=CC=C2C(N=C(NC(C3=CC=CC=C3)=O)N2CCCC4=CC=CC=C4)=C1)OC
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: | BRD4770 is a histone methyltransferase G9a inhibitor. |
| In vitro activity: | This study observed greatly elevated levels of monoubiquitinated FANCD2 and FANCI in the chromatin fraction of cells treated with BRD4770 alone (Figure 2A, compare lanes 3 and 9). This study observed a striking increase in the percentage of nuclei exhibiting greater than 5 FANCD2 foci in both U2OS and BJ-TERT cells following BRD4770 treatment (Figure 2B and Supplementary Figure 1A and 1B). Levels of FANCD2 nuclear foci formation in cells treated with BRD4770 alone were comparable to that observed following MMC treatment (Supplementary Figure 1A and 1B). These results identify BRD4770 as a major inducer of FANCD2 monoubiquitination and nuclear foci formation and strongly suggest that changes in histone methylation status are a critical determinant in the activation of the FA pathway. Consistent with BRD4770 functioning via the modification of chromatin structure, this study observed a distinct change in the staining pattern of the heterochromatin marker HP1α following BRD4770 treatment (Supplementary Figure 1C). Reference: Oncotarget. 2017 Sep 29; 8(44): 76443–76457. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652718/ |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 12.7 | 171.72 | |
| DMF | 20.0 | 48.37 | |
| DMF:PBS (pH 7.2) (1:2) | 0.3 | 0.60 |
The following data is based on the product molecular weight 413.47 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. Vierra DA, Garzon JL, Rego MA, Adroved MM, Mauro M, Howlett NG. Modulation of the Fanconi anemia pathway via chemically induced changes in chromatin structure. Oncotarget. 2017 Jul 22;8(44):76443-76457. doi: 10.18632/oncotarget.19470. PMID: 29100324; PMCID: PMC5652718. 2. Yuan Y, Tang AJ, Castoreno AB, Kuo SY, Wang Q, Kuballa P, Xavier R, Shamji AF, Schreiber SL, Wagner BK. Gossypol and an HMT G9a inhibitor act in synergy to induce cell death in pancreatic cancer cells. Cell Death Dis. 2013 Jun 27;4(6):e690. doi: 10.1038/cddis.2013.191. PMID: 23807219; PMCID: PMC3702302. |
| In vitro protocol: | 1. Vierra DA, Garzon JL, Rego MA, Adroved MM, Mauro M, Howlett NG. Modulation of the Fanconi anemia pathway via chemically induced changes in chromatin structure. Oncotarget. 2017 Jul 22;8(44):76443-76457. doi: 10.18632/oncotarget.19470. PMID: 29100324; PMCID: PMC5652718. 2. Yuan Y, Tang AJ, Castoreno AB, Kuo SY, Wang Q, Kuballa P, Xavier R, Shamji AF, Schreiber SL, Wagner BK. Gossypol and an HMT G9a inhibitor act in synergy to induce cell death in pancreatic cancer cells. Cell Death Dis. 2013 Jun 27;4(6):e690. doi: 10.1038/cddis.2013.191. PMID: 23807219; PMCID: PMC3702302. |
| In vivo protocol: | TBD |
1: Yuan Y, Tang AJ, Castoreno AB, Kuo SY, Wang Q, Kuballa P, Xavier R, Shamji AF, Schreiber SL, Wagner BK. Gossypol and an HMT G9a inhibitor act in synergy to induce cell death in pancreatic cancer cells. Cell Death Dis. 2013 Jun 27;4:e690. doi: 10.1038/cddis.2013.191. PubMed PMID: 23807219; PubMed Central PMCID: PMC3702302.
2: Yuan Y, Wang Q, Paulk J, Kubicek S, Kemp MM, Adams DJ, Shamji AF, Wagner BK, Schreiber SL. A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma. ACS Chem Biol. 2012 Jul 20;7(7):1152-7. doi: 10.1021/cb300139y. Epub 2012 Apr 30. PubMed PMID: 22536950; PubMed Central PMCID: PMC3401036.
