IUPAC/Chemical Name
ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate
InChi Key
UYBRROMMFMPJAN-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H20N6O4S/c1-5-27-17(24)18-15-9-14(21-23-11(3)19-20-16(15)23)12-7-6-10(2)13(8-12)22-28(4,25)26/h6-9,22H,5H2,1-4H3,(H,18,24)
SMILES Code
O=C(OCC)NC1=CC(C2=CC=C(C)C(NS(=O)(C)=O)=C2)=NN3C1=NN=C3C
Appearance
white 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
Biological target:
Bromosporine is a broad spectrum inhibitor for bromodomains with IC50 of 0.41 μM, 0.29 μM, 0.122 μM and 0.017 μM for BRD2, BRD4, BRD9 and CECR2, respectively.
In vitro activity:
After treating with 2.5 μM bromosporine for 72h, the percentage of GFP-expressing cells was measured by flow cytometry, which represented the expression of HIV-1 LTR-driven GFP. The percentage of GFP-positive cells increased to 85.6% as compared to mock treatment (Figure 1B). In addition, dose- and time-dependent effects of bromosporine on HIV-1 reactivation were also observed in C11 cells (Figure 1C and 1D) (Supplementary Figure 1). As shown in Figure 1C, the percentage of GFP-positive cells dramatically raised from 6.88% to 87.7% as the concentration of bromosporine increased from 0.1 μM to 2.5 μM. And as shown in Figure Figure1D, after C11 cells were treated with 2.5 μM bromosporine, the percentage of GFP-positive cells increased as a function of time.
Reference: Oncotarget. 2017 Nov 7; 8(55): 94104–94116. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706859/
In vivo activity:
Following the in vitro effect of 5-FU with bromosporine, the effect of the drugs together as well as individual exposures were studied in the mouse model administered the drugs as described in the materials section. The combinatorial approach was found to inhibit the tumor growth of the HCT116 xenograft against individual drugs (Fig. 4A). This was further confirmed by data from body weight with an absence of higher toxicity (Fig. 4B). Tumor protein analysis revealed that cleaved caspase 3 was significantly increased in combination treatment group (Fig. 4C). These findings show that the synergistic action of the drug combination of bromosporine with 5-FU in vivo.
Reference: Biochem Biophys Res Commun. 2020 Jan 22;521(4):840-845. https://pubmed.ncbi.nlm.nih.gov/31708100/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
41.0 |
101.47 |
| DMSO:PBS (pH 7.2) (1:1) |
0.5 |
1.24 |
| DMF |
30.0 |
74.18 |
| Ethanol |
0.3 |
0.62 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
404.44
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. Cheng X, Huang Z, Long D, Jin W. BET inhibitor bromosporine enhances 5-FU effect in colorectal cancer cells. Biochem Biophys Res Commun. 2020 Jan 22;521(4):840-845. doi: 10.1016/j.bbrc.2019.11.009. Epub 2019 Nov 7. PMID: 31708100.
2. Pan H, Lu P, Shen Y, Wang Y, Jiang Z, Yang X, Zhong Y, Yang H, Khan IU, Zhou M, Li B, Zhang Z, Xu J, Lu H, Zhu H. The bromodomain and extraterminal domain inhibitor bromosporine synergistically reactivates latent HIV-1 in latently infected cells. Oncotarget. 2017 Oct 6;8(55):94104-94116. doi: 10.18632/oncotarget.21585. PMID: 29212213; PMCID: PMC5706859.
In vitro protocol:
1. Cheng X, Huang Z, Long D, Jin W. BET inhibitor bromosporine enhances 5-FU effect in colorectal cancer cells. Biochem Biophys Res Commun. 2020 Jan 22;521(4):840-845. doi: 10.1016/j.bbrc.2019.11.009. Epub 2019 Nov 7. PMID: 31708100.
2. Pan H, Lu P, Shen Y, Wang Y, Jiang Z, Yang X, Zhong Y, Yang H, Khan IU, Zhou M, Li B, Zhang Z, Xu J, Lu H, Zhu H. The bromodomain and extraterminal domain inhibitor bromosporine synergistically reactivates latent HIV-1 in latently infected cells. Oncotarget. 2017 Oct 6;8(55):94104-94116. doi: 10.18632/oncotarget.21585. PMID: 29212213; PMCID: PMC5706859.
In vivo protocol:
1. Cheng X, Huang Z, Long D, Jin W. BET inhibitor bromosporine enhances 5-FU effect in colorectal cancer cells. Biochem Biophys Res Commun. 2020 Jan 22;521(4):840-845. doi: 10.1016/j.bbrc.2019.11.009. Epub 2019 Nov 7. PMID: 31708100.
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