Synonym
SB747651A dihydrochloride; SB 747651A dihydrochloride; SB-747651A dihydrochloride
IUPAC/Chemical Name
2-(4-Amino-1,2,5-oxadiazol-3-yl)-1-ethyl-N-4-piperidinyl-1H-imidazo[4,5-c]pyridine-7-methanamine dihydrochloride
InChi Key
NRRCQHARLPNLHJ-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H22N8O.2ClH/c1-2-24-14-10(8-20-11-3-5-18-6-4-11)7-19-9-12(14)21-16(24)13-15(17)23-25-22-13;;/h7,9,11,18,20H,2-6,8H2,1H3,(H2,17,23);2*1H
SMILES Code
CCN1C(C2=NON=C2N)=NC3=C1C(CNC4CCNCC4)=CN=C3.[H]Cl.[H]Cl
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 and water
Shelf Life
>3 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
2934.99.03.00
Biological target:
SB-747651A dihydrochloride is a potent, ATP-competitive mitogen- and stress-activated kinase 1 (MSK1) inhibitor (IC50 = 11 nM in an in vitro kinase assay). SB-747651A dihydrochloride targets the N-terminal kinase domain and inhibits MSK1, MSK2, PKA, PKB, RSK and p70S6K activity in cells. SB-747651A dihydrochloride blocks IL-10 production in macrophages.
In vitro activity:
SB-747651A represents a useful tool to study MSK function in cells. SB-747651A inhibited MSK1, PRK2, RSK1, p70S6K, and ROCK-II. In cells, SB-747651A fully inhibited MSK activity at 5-10 μM. SB-747651A was found to inhibit the production of interleukin-10 in wild-type, but not MSK1/2-knockout, macrophages following LPS stimulation.
Reference: Biochem J. 2012 Jan 1;441(1):347-57. https://pubmed.ncbi.nlm.nih.gov/21970321/
In vivo activity:
SB-747651A inhibited MSK1, which altered multiple stages of the neutrophil recruitment process. SB-747651A treatment enhanced neutrophil adhesion but delayed emigration. SB-747651A altered the integrin αMβ₂ expression, affecting neutrophil migration and transmigration time. SB-747651A impacted the speed and timing of neutrophil migration in response to the CXCL2 chemotactic gradient.
Reference: Int J Mol Sci. 2017 Oct 17;18(10):2163. https://pubmed.ncbi.nlm.nih.gov/29039777/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
20.8 |
50.00 |
| Water |
20.8 |
50.00 |
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
415.32
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. Zhang S, Pan C, Shang Q, Wang W, Hu T, Liu P, Chen S, Wang J, Fang Q. Overexpressed mitogen-and stress-activated protein kinase 1 promotes the resistance of cytarabine in acute myeloid leukemia through brahma related gene 1-mediated upregulation of heme oxygenase-1. Eur J Pharmacol. 2022 Feb 15;917:174722. doi: 10.1016/j.ejphar.2021.174722. Epub 2021 Dec 23. PMID: 34953799.
2. Naqvi S, Macdonald A, McCoy CE, Darragh J, Reith AD, Arthur JS. Characterization of the cellular action of the MSK inhibitor SB-747651A. Biochem J. 2012 Jan 1;441(1):347-57. doi: 10.1042/BJ20110970. PMID: 21970321.
3. Knudsen AM, Boldt HB, Jakobsen EV, Kristensen BW. The multi-target small-molecule inhibitor SB747651A shows in vitro and in vivo anticancer efficacy in glioblastomas. Sci Rep. 2021 Mar 16;11(1):6066. doi: 10.1038/s41598-021-85536-4. PMID: 33727611; PMCID: PMC7966768.
4. Hossain M, Omran E, Xu N, Liu L. The Specific Mitogen- and Stress-Activated Protein Kinase MSK1 Inhibitor SB-747651A Modulates Chemokine-Induced Neutrophil Recruitment. Int J Mol Sci. 2017 Oct 17;18(10):2163. doi: 10.3390/ijms18102163. PMID: 29039777; PMCID: PMC5666844.
In vitro protocol:
1. Zhang S, Pan C, Shang Q, Wang W, Hu T, Liu P, Chen S, Wang J, Fang Q. Overexpressed mitogen-and stress-activated protein kinase 1 promotes the resistance of cytarabine in acute myeloid leukemia through brahma related gene 1-mediated upregulation of heme oxygenase-1. Eur J Pharmacol. 2022 Feb 15;917:174722. doi: 10.1016/j.ejphar.2021.174722. Epub 2021 Dec 23. PMID: 34953799.
2. Naqvi S, Macdonald A, McCoy CE, Darragh J, Reith AD, Arthur JS. Characterization of the cellular action of the MSK inhibitor SB-747651A. Biochem J. 2012 Jan 1;441(1):347-57. doi: 10.1042/BJ20110970. PMID: 21970321.
In vivo protocol:
1. Knudsen AM, Boldt HB, Jakobsen EV, Kristensen BW. The multi-target small-molecule inhibitor SB747651A shows in vitro and in vivo anticancer efficacy in glioblastomas. Sci Rep. 2021 Mar 16;11(1):6066. doi: 10.1038/s41598-021-85536-4. PMID: 33727611; PMCID: PMC7966768.
2. Hossain M, Omran E, Xu N, Liu L. The Specific Mitogen- and Stress-Activated Protein Kinase MSK1 Inhibitor SB-747651A Modulates Chemokine-Induced Neutrophil Recruitment. Int J Mol Sci. 2017 Oct 17;18(10):2163. doi: 10.3390/ijms18102163. PMID: 29039777; PMCID: PMC5666844.
1: Zhang S, Pan C, Shang Q, Wang W, Hu T, Liu P, Chen S, Wang J, Fang Q. Overexpressed mitogen-and stress-activated protein kinase 1 promotes the resistance of cytarabine in acute myeloid leukemia through brahma related gene 1-mediated upregulation of heme oxygenase-1. Eur J Pharmacol. 2022 Feb 15;917:174722. doi: 10.1016/j.ejphar.2021.174722. Epub 2021 Dec 23. PMID: 34953799.
2: Knudsen AM, Boldt HB, Jakobsen EV, Kristensen BW. The multi-target small- molecule inhibitor SB747651A shows in vitro and in vivo anticancer efficacy in glioblastomas. Sci Rep. 2021 Mar 16;11(1):6066. doi: 10.1038/s41598-021-85536-4. PMID: 33727611; PMCID: PMC7966768.
3: Lin M, Huang C, Ren W, Chen J, Xia N, Zhong S. Mitogen- and Stress-Activated Protein Kinase 1 Mediates Alcohol-Upregulated Transcription of Brf1 and tRNA Genes to Cause Phenotypic Alteration. Oxid Med Cell Longev. 2020 Jun 27;2020:2067959. doi: 10.1155/2020/2067959. PMID: 32685086; PMCID: PMC7336232.
4: Feiner B, Chase KA, Melbourne JK, Rosen C, Sharma RP. Risperidone effects on heterochromatin: the role of kinase signaling. Clin Exp Immunol. 2019 Apr;196(1):67-75. doi: 10.1111/cei.13250. Epub 2019 Feb 3. PMID: 30714144; PMCID: PMC6422669.
5: Hossain M, Omran E, Xu N, Liu L. The Specific Mitogen- and Stress-Activated Protein Kinase MSK1 Inhibitor SB-747651A Modulates Chemokine-Induced Neutrophil Recruitment. Int J Mol Sci. 2017 Oct 17;18(10):2163. doi: 10.3390/ijms18102163. PMID: 29039777; PMCID: PMC5666844.
6: Bhat N, Park J, Zoghbi HY, Arthur JS, Zaret KS. The Chromatin Modifier MSK1/2 Suppresses Endocrine Cell Fates during Mouse Pancreatic Development. PLoS One. 2016 Dec 14;11(12):e0166703. doi: 10.1371/journal.pone.0166703. PMID: 27973548; PMCID: PMC5156359.
7: Zhao C, Hui W, Fernandes MJ, Poubelle PE, Bourgoin SG. Lysophosphatidic acid- induced IL-8 secretion involves MSK1 and MSK2 mediated activation of CREB1 in human fibroblast-like synoviocytes. Biochem Pharmacol. 2014 Jul 1;90(1):62-72. doi: 10.1016/j.bcp.2014.04.012. Epub 2014 Apr 30. PMID: 24792438.
8: Johnson J, Shi Z, Liu Y, Stack MS. Inhibitors of NF-kappaB reverse cellular invasion and target gene upregulation in an experimental model of aggressive oral squamous cell carcinoma. Oral Oncol. 2014 May;50(5):468-77. doi: 10.1016/j.oraloncology.2014.02.004. Epub 2014 Feb 28. PMID: 24582884; PMCID: PMC4001858.
9: Naqvi S, Macdonald A, McCoy CE, Darragh J, Reith AD, Arthur JS. Characterization of the cellular action of the MSK inhibitor SB-747651A. Biochem J. 2012 Jan 1;441(1):347-57. doi: 10.1042/BJ20110970. PMID: 21970321.
