WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406745
CAS#: 1910124-24-1
Description: GSK6853 is a potent (300 pM), soluble, cell active (20 nM), and highly selective inhibitor of the BRPF1 bromodomain, and demonstrated properties suitable for cellular and in vivo studies. The BRPF (Bromodomain and PHD Fingercontaining) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. BRPF1 (bromodomain and PHD finger containing protein 1) is involved in the epigenetic regulation of gene expression and have been implicated in human cancer.
MedKoo Cat#: 406745
Name: GSK6853
CAS#: 1910124-24-1
Chemical Formula: C22H27N5O3
Exact Mass: 409.2114
Molecular Weight: 409.49
Elemental Analysis: C, 64.53; H, 6.65; N, 17.10; O, 11.72
Synonym: GSK6853; GSK 6853; GSK-6853.
IUPAC/Chemical Name: (R)-N-(1,3-dimethyl-6-(2-methylpiperazin-1-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-2-methoxybenzamide
InChi Key: FQWDVNSBYDXPIO-CQSZACIVSA-N
InChi Code: InChI=1S/C22H27N5O3/c1-14-13-23-9-10-27(14)17-12-19-18(25(2)22(29)26(19)3)11-16(17)24-21(28)15-7-5-6-8-20(15)30-4/h5-8,11-12,14,23H,9-10,13H2,1-4H3,(H,24,28)/t14-/m1/s1
SMILES Code: O=C(NC1=C(N2[C@H](C)CNCC2)C=C(N3C)C(N(C)C3=O)=C1)C4=CC=CC=C4OC
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
| Biological target: | GSK6853 is a potent and selective inhibitor of the BRPF1 bromodomain. |
| In vitro activity: | Compounds 34 and 38 were assessed in a cellular protein interaction assay measuring the displacement of NanoLuc-tagged BRPF1 bromodomain from Halo-tagged histone H3.3 to demonstrate cell permeability and disruption of chromatin binding (Supplementary Methods, Supporting Information). Compound 34 exhibited potent inhibition (Figure S7) with pIC50 7.7, a 50-fold improvement over 1. Reference: ACS Med Chem Lett. 2016 May 9;7(6):552-7. https://pubmed.ncbi.nlm.nih.gov/27326325/ |
| In vivo activity: | To assess the suitability of compound 34 for in vivo studies, its DMPK characteristics were determined in male CD1 mice via iv, po, and ip administration. The results indicate that the ip route of administration would be suitable for dosing this molecule in potential PK/PD models. In order to be able to compare biochemical potency measurements to free blood concentrations, the fraction unbound (fub) in the CD1 mouse was also determined with a resulting value of 7.9% (Table 7 and Table S4). Reference: ACS Med Chem Lett. 2016 May 9;7(6):552-7. https://pubmed.ncbi.nlm.nih.gov/27326325/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 30.0 | 73.26 | |
| DMSO | 42.99 | 104.98 | |
| Ethanol | 55.5 | 135.53 | |
| Ethanol:PBS (pH 7.2) (1:1) | 0.5 | 1.22 |
The following data is based on the product molecular weight 409.49 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. Bamborough P, Barnett HA, Becher I, Bird MJ, Chung CW, Craggs PD, Demont EH, Diallo H, Fallon DJ, Gordon LJ, Grandi P, Hobbs CI, Hooper-Greenhill E, Jones EJ, Law RP, Le Gall A, Lugo D, Michon AM, Mitchell DJ, Prinjha RK, Sheppard RJ, Watson AJ, Watson RJ. GSK6853, a Chemical Probe for Inhibition of the BRPF1 Bromodomain. ACS Med Chem Lett. 2016 May 9;7(6):552-7. doi: 10.1021/acsmedchemlett.6b00092. PMID: 27326325; PMCID: PMC4904261. |
| In vitro protocol: | 1. Bamborough P, Barnett HA, Becher I, Bird MJ, Chung CW, Craggs PD, Demont EH, Diallo H, Fallon DJ, Gordon LJ, Grandi P, Hobbs CI, Hooper-Greenhill E, Jones EJ, Law RP, Le Gall A, Lugo D, Michon AM, Mitchell DJ, Prinjha RK, Sheppard RJ, Watson AJ, Watson RJ. GSK6853, a Chemical Probe for Inhibition of the BRPF1 Bromodomain. ACS Med Chem Lett. 2016 May 9;7(6):552-7. doi: 10.1021/acsmedchemlett.6b00092. PMID: 27326325; PMCID: PMC4904261. |
| In vivo protocol: | 1. Bamborough P, Barnett HA, Becher I, Bird MJ, Chung CW, Craggs PD, Demont EH, Diallo H, Fallon DJ, Gordon LJ, Grandi P, Hobbs CI, Hooper-Greenhill E, Jones EJ, Law RP, Le Gall A, Lugo D, Michon AM, Mitchell DJ, Prinjha RK, Sheppard RJ, Watson AJ, Watson RJ. GSK6853, a Chemical Probe for Inhibition of the BRPF1 Bromodomain. ACS Med Chem Lett. 2016 May 9;7(6):552-7. doi: 10.1021/acsmedchemlett.6b00092. PMID: 27326325; PMCID: PMC4904261. |
GSK6853, a Chemical Probe for Inhibition of the BRPF1 Bromodomain
Paul Bamborough, Heather A. Barnett, Isabelle Becher, Mark J. Bird, Chun-wa Chung, Peter D. Craggs, Emmanuel H. Demont, Hawa Diallo, David J. Fallon, Laurie J. Gordon, Paola Grandi, Clare I. Hobbs, Edward Hooper-Greenhill, Emma J. Jones, Robert P. Law, Armelle Le Gall, David Lugo, Anne-Marie Michon, Darren J. Mitchell, Rab K. Prinjha, Robert J. Sheppard, Allan J. B. Watson, and Robert J. Watson
Publication Date (Web): May 9, 2016 (Featured Letter)
DOI: 10.1021/acsmedchemlett.6b00092
