WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H407158
CAS#: 926259-99-6
Description: BG45 is a potent and selective HDAC3 inhibitor inhibitor with selectivity for HDAC3 (IC50 = 289 nM) over HDAC1, 2. BG45 did not inihibit HDAC6. BG45 signigicantly inhibited tumor growth in a mouse model of multiple myeloma either alone and synergistically in combination with bortezomib. HDAC3 represents a promising therapeutic target, and validate a prototype novel HDAC3 inhibitor BG45 in MM.
Hodoodo Cat#: H407158
Name: BG45
CAS#: 926259-99-6
Chemical Formula: C11H10N4O
Exact Mass: 214.09
Molecular Weight: 214.230
Elemental Analysis: C, 61.67; H, 4.71; N, 26.15; O, 7.47
Synonym: BG45; BG-45; BG 45.
IUPAC/Chemical Name: N-(2-Aminophenyl)pyrazine-2-carboxamide
InChi Key: LMWPVSNHKACEKW-UHFFFAOYSA-N
InChi Code: InChI=1S/C11H10N4O/c12-8-3-1-2-4-9(8)15-11(16)10-7-13-5-6-14-10/h1-7H,12H2,(H,15,16)
SMILES Code: O=C(C1=NC=CN=C1)NC2=CC=CC=C2N
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: | BG45 is an HDAC class I inhibitor with selectivity for HDAC3 (IC50 = 289 nM). |
| In vitro activity: | To both further validate the role of HDAC3 in MM biology and provide the framework for derived clinical trials targeting HDAC3, ortho-amino anilide BG45 has recently been produced and validated to be an HDAC class I inhibitor with selectivity for HDAC3 (IC50 = 289nM) over HDAC1, 2 (Supplemental Figure 2B, Table 1) 12. Consistent with HDAC3 knockdown data above, BG45 significantly inhibited MM cell growth in a dose-dependent fashion, as assessed by MTT assay (Figure 4A). Importantly, BG45 also triggered a potent growth inhibitory effect against patient-derived MM cells (Figure 4B), without affecting normal donor PBMCs (Figure 4C). These results suggest that BG45 selectively targets MM cells. It was next examined whether BG45 overcomes the antiapoptotic effect of BMSCs 20: importantly, BG45 in a dose-dependent fashion markedly inhibited MM cell growth even in the presence of BMSCs (Figure 4D), associated with caspase-3/PARP cleavage (Figure 4E). These results suggest BG45 induces caspasedependent apoptosis in MM cells. Reference: Leukemia. 2014 Mar; 28(3): 680–689. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165599/ |
| In vivo activity: | In this study, the relationship between HDAC activity and synapse-related genes and proteins were examined by the administration of a class I HDAC inhibitor, BG45, in the exogenous Aβ-treated cells and mice. Fifteen mice were divided into control group, HF-488Aβ1–40-treated group (HF-488-Aβ group) and BG45 administration group (HF-488-Aβ + BG45 group) for following experiments. The levels of HDAC1 and HDAC2 were detected in the exogenous Aβ-treated mice with or without the administration of BG45. The results showed the levels of HDAC1 and HDAC2 in the exogenous Aβ treated group were significantly higher than those in the control group (p < 0.05, p < 0.05; see Figures 7A–C). In the BG45-treated group, the levels were slightly lower than those in the Aβtreated group (p < 0.05, p < 0.05). Meanwhile, the effect of BG45 on the synapse-related protein was detected. The expression of spinophilin was significantly decreased by exogenous HF-488-Aβ1–40, while BG45 prevented the effect from the Aβ1–40 (p < 0.01). The expression of PSD-95 and SYP was also down-regulated by exogenous Aβ (p < 0.05, p < 0.05), whereas BG45 increased the expression of PSD-95 and SYP (p < 0.05, p < 0.05; see Figures 7D–G). BG45 might be a potential therapeutic agent for the treatment of an early stage of Aβ-related neurodegenerative disease. Reference: Front Aging Neurosci. 2020; 12: 619866. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852506/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 40.0 | 187.72 |
The following data is based on the product molecular weight 214.23 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. Minami J, Suzuki R, Mazitschek R, Gorgun G, Ghosh B, Cirstea D, Hu Y, Mimura N, Ohguchi H, Cottini F, Jakubikova J, Munshi NC, Haggarty SJ, Richardson PG, Hideshima T, Anderson KC. Histone deacetylase 3 as a novel therapeutic target in multiple myeloma. Leukemia. 2014 Mar;28(3):680-9. doi: 10.1038/leu.2013.231. Epub 2013 Aug 5. PMID: 23913134; PMCID: PMC4165599. 2. Han Y, Chen L, Guo Y, Wang C, Zhang C, Kong L, Ma H. Class I HDAC Inhibitor Improves Synaptic Proteins and Repairs Cytoskeleton Through Regulating Synapse-Related Genes In vitro and In vivo. Front Aging Neurosci. 2021 Jan 19;12:619866. doi: 10.3389/fnagi.2020.619866. PMID: 33542682; PMCID: PMC7852506 |
| In vitro protocol: | 1. Minami J, Suzuki R, Mazitschek R, Gorgun G, Ghosh B, Cirstea D, Hu Y, Mimura N, Ohguchi H, Cottini F, Jakubikova J, Munshi NC, Haggarty SJ, Richardson PG, Hideshima T, Anderson KC. Histone deacetylase 3 as a novel therapeutic target in multiple myeloma. Leukemia. 2014 Mar;28(3):680-9. doi: 10.1038/leu.2013.231. Epub 2013 Aug 5. PMID: 23913134; PMCID: PMC4165599. 2. Han Y, Chen L, Guo Y, Wang C, Zhang C, Kong L, Ma H. Class I HDAC Inhibitor Improves Synaptic Proteins and Repairs Cytoskeleton Through Regulating Synapse-Related Genes In vitro and In vivo. Front Aging Neurosci. 2021 Jan 19;12:619866. doi: 10.3389/fnagi.2020.619866. PMID: 33542682; PMCID: PMC7852506 |
| In vivo protocol: | 1. Minami J, Suzuki R, Mazitschek R, Gorgun G, Ghosh B, Cirstea D, Hu Y, Mimura N, Ohguchi H, Cottini F, Jakubikova J, Munshi NC, Haggarty SJ, Richardson PG, Hideshima T, Anderson KC. Histone deacetylase 3 as a novel therapeutic target in multiple myeloma. Leukemia. 2014 Mar;28(3):680-9. doi: 10.1038/leu.2013.231. Epub 2013 Aug 5. PMID: 23913134; PMCID: PMC4165599. 2. Han Y, Chen L, Guo Y, Wang C, Zhang C, Kong L, Ma H. Class I HDAC Inhibitor Improves Synaptic Proteins and Repairs Cytoskeleton Through Regulating Synapse-Related Genes In vitro and In vivo. Front Aging Neurosci. 2021 Jan 19;12:619866. doi: 10.3389/fnagi.2020.619866. PMID: 33542682; PMCID: PMC7852506 |
1: Minami J, Suzuki R, Mazitschek R, Gorgun G, Ghosh B, Cirstea D, Hu Y, Mimura
N, Ohguchi H, Cottini F, Jakubikova J, Munshi NC, Haggarty SJ, Richardson PG,
Hideshima T, Anderson KC. Histone deacetylase 3 as a novel therapeutic target in
multiple myeloma. Leukemia. 2014 Mar;28(3):680-9. doi: 10.1038/leu.2013.231. Epub
2013 Aug 5. PubMed PMID: 23913134; PubMed Central PMCID: PMC4165599.
