Synonym
BRD 3308; BRD-3308; BRD3308
IUPAC/Chemical Name
4-Acetylamino-N-(2-amino-4-fluorophenyl)-benzamide
InChi Key
RRJDFENBXIEAPD-UHFFFAOYSA-N
InChi Code
InChI=1S/C15H14FN3O2/c1-9(20)18-12-5-2-10(3-6-12)15(21)19-14-7-4-11(16)8-13(14)17/h2-8H,17H2,1H3,(H,18,20)(H,19,21)
SMILES Code
O=C(NC1=CC=C(F)C=C1N)C2=CC=C(NC(C)=O)C=C2
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
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:
BRD3308 is a highly selective HDAC3 inhibitor with an IC50 of 54 nM and 23-fold selectivity for HDAC3 over HDAC1 (IC50 of 1.26 μM) or HDAC2 (IC50 of 1.34 μM).
In vitro activity:
The induction of viral outgrowth following the exposure of patients' resting CD4+ T cells to the HDAC3 selective inhibitor BRD3308 was examined. Cells from four patients (Pt 1, Pt 2, Pt 3, and Pt 4) were exposed to 15 µM of BRD3308. In all four patients, 15 µM of BRD3308 induced a similar or greater amount of viral outgrowth as exposure to SAHA (Fig. 7A). Furthermore, PBMCs exposed to 5 µM, 10 µM, 15 µM, or 30 µM BRD3308 for 24 hours did not show a significant decrease in viability when compared to PBMCs exposed to the vehicle control (0.015% DMSO) (Fig. 7B). Additionally, the percent of cells expressing the T cell activation markers CD69, CD25, and HLA-DR did not increase following treatment with 15 µM of BRD3308 (data not shown). This data demonstrates that exposure to an HDAC3 selective inhibitor allows the recovery of latent HIV-1 from patient cells at a similar frequency as the selective Class I HDAC inhibitor SAHA without decreasing cell viability or inducing cell activation, in contrast to the absence of viral induction observed following exposure to an inhibitor specific for HDAC1 and −2.
Reference: PLoS One. 2014 Aug 19;9(8):e102684. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25136952/
In vivo activity:
The ability of a selective HDAC3 inhibitor, BRD3308, to reduce hyperglycaemia and increase insulin secretion was tested in a rat model of type 2 diabetes. At diabetes onset, an ambulatory hyperglycaemic clamp was performed. HDAC3 inhibition improved hyperglycaemia over the study period without affecting weight gain. At the end of the hyperglycaemic clamp, circulating insulin levels were significantly higher in BRD3308-treated rats. Pancreatic insulin staining and contents were also significantly higher. These findings highlight HDAC3 as a key therapeutic target for β-cell protection in type 2 diabetes.
Reference: Diabetes Obes Metab. 2015 Jul;17(7):703-7. https://doi.org/10.1111/dom.12470
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
57.0 |
198.41 |
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
287.29
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 |
In vitro protocol:
1. Barton KM, Archin NM, Keedy KS, Espeseth AS, Zhang YL, Gale J, Wagner FF, Holson EB, Margolis DM. Selective HDAC inhibition for the disruption of latent HIV-1 infection. PLoS One. 2014 Aug 19;9(8):e102684. doi: 10.1371/journal.pone.0102684. PMID: 25136952; PMCID: PMC4138023.
2. Wagner FF, Lundh M, Kaya T, McCarren P, Zhang YL, Chattopadhyay S, Gale JP, Galbo T, Fisher SL, Meier BC, Vetere A, Richardson S, Morgan NG, Christensen DP, Gilbert TJ, Hooker JM, Leroy M, Walpita D, Mandrup-Poulsen T, Wagner BK, Holson EB. An Isochemogenic Set of Inhibitors To Define the Therapeutic Potential of Histone Deacetylases in β-Cell Protection. ACS Chem Biol. 2016 Feb 19;11(2):363-74. doi: 10.1021/acschembio.5b00640. Epub 2015 Dec 7. PMID: 26640968.
In vivo protocol:
1. Lundh M, Galbo T, Poulsen SS, Mandrup-Poulsen T. Histone deacetylase 3 inhibition improves glycaemia and insulin secretion in obese diabetic rats. Diabetes Obes Metab. 2015 Jul;17(7):703-7. doi: 10.1111/dom.12470. Epub 2015 May 26. PMID: 25846481.
2. Dirice E, Ng RWS, Martinez R, Hu J, Wagner FF, Holson EB, Wagner BK, Kulkarni RN. Isoform-selective inhibitor of histone deacetylase 3 (HDAC3) limits pancreatic islet infiltration and protects female nonobese diabetic mice from diabetes. J Biol Chem. 2017 Oct 27;292(43):17598-17608. doi: 10.1074/jbc.M117.804328. Epub 2017 Aug 31. PMID: 28860191; PMCID: PMC5663865.
1: Dirice E, Ng RWS, Martinez R, Hu J, Wagner FF, Holson EB, Wagner BK, Kulkarni RN. Isoform-selective inhibitor of histone deacetylase 3 (HDAC3) limits pancreatic islet infiltration and protects female nonobese diabetic mice from diabetes. J Biol Chem. 2017 Oct 27;292(43):17598-17608. doi: 10.1074/jbc.M117.804328. Epub 2017 Aug 31. PubMed PMID: 28860191; PubMed Central PMCID: PMC5663865.
2: Wagner FF, Lundh M, Kaya T, McCarren P, Zhang YL, Chattopadhyay S, Gale JP, Galbo T, Fisher SL, Meier BC, Vetere A, Richardson S, Morgan NG, Christensen DP, Gilbert TJ, Hooker JM, Leroy M, Walpita D, Mandrup-Poulsen T, Wagner BK, Holson EB. An Isochemogenic Set of Inhibitors To Define the Therapeutic Potential of Histone Deacetylases in β-Cell Protection. ACS Chem Biol. 2016 Feb 19;11(2):363-74. doi: 10.1021/acschembio.5b00640. Epub 2015 Dec 7. PubMed PMID: 26640968.
3: Lundh M, Galbo T, Poulsen SS, Mandrup-Poulsen T. Histone deacetylase 3 inhibition improves glycaemia and insulin secretion in obese diabetic rats. Diabetes Obes Metab. 2015 Jul;17(7):703-7. doi: 10.1111/dom.12470. Epub 2015 May 26. PubMed PMID: 25846481.
4: Barton KM, Archin NM, Keedy KS, Espeseth AS, Zhang YL, Gale J, Wagner FF, Holson EB, Margolis DM. Selective HDAC inhibition for the disruption of latent HIV-1 infection. PLoS One. 2014 Aug 19;9(8):e102684. doi: 10.1371/journal.pone.0102684. eCollection 2014. PubMed PMID: 25136952; PubMed Central PMCID: PMC4138023.
