WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 555971
CAS#: 2088410-46-0
Description: GSK620 is a Potent, selective, and Highly Soluble Bromo and Extraterminal Domain (BET) Second Bromodomain (BD2) Inhibitor. GSK620 showed an anti-inflammatory phenotype in human whole blood, confirming their cellular target engagement. Excellent broad selectivity, developability, and in vivo oral pharmacokinetics characterize these tools, which we hope will be of broad utility to the field of epigenetics research.
MedKoo Cat#: 555971
Name: GSK620
CAS#: 2088410-46-0
Chemical Formula: C18H19N3O3
Exact Mass: 325.1426
Molecular Weight: 325.368
Elemental Analysis: C, 66.45; H, 5.89; N, 12.91; O, 14.75
Synonym: GSK620; GSK-620; GSK 620;
IUPAC/Chemical Name: 1-Benzyl-N5-cyclopropyl-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide
InChi Key: QZZCUOVXHPAQRQ-UHFFFAOYSA-N
InChi Code: InChI=1S/C18H19N3O3/c1-19-17(23)15-9-13(16(22)20-14-7-8-14)11-21(18(15)24)10-12-5-3-2-4-6-12/h2-6,9,11,14H,7-8,10H2,1H3,(H,19,23)(H,20,22)
SMILES Code: O=C(C1=CC(C(NC2CC2)=O)=CN(CC3=CC=CC=C3)C1=O)NC
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: To be determined
Shelf Life: >2 years if stored properly
Drug Formulation: To be determined
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: | GSK620 is a potent and orally active pan-BD2 inhibitor with excellent broad selectivity, developability and in vivo oral pharmacokinetics. |
| In vitro activity: | This culminated in two tool molecules, 20 (GSK620) and 56 (GSK549), which showed an anti-inflammatory phenotype in human whole blood, confirming their cellular target engagement. Reference: J Med Chem. 2020 Sep 10;63(17):9093-9126. https://pubmed.ncbi.nlm.nih.gov/32702236/ |
| In vivo activity: | This study initially tested GSK620 in a collagen-induced arthritis model in rats, a commonly used model of pathologies such as rheumatoid arthritis where an immunological response manifests as inflammatory arthritis associated with progressive cartilaginous destruction, joint swelling, and ultimately ankylosis. In this model, GSK620 led to a significant dose-dependent inhibition of both the arthritic score and IgG1 production in response to the immunisation (fig. S17A-E). Reference: Science. 2020 Apr 24;368(6489):387-394. https://pubmed.ncbi.nlm.nih.gov/32193360/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 63.75 | 195.93 |
The following data is based on the product molecular weight 325.368 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. Seal JT, Atkinson SJ, Aylott H, Bamborough P, Chung CW, Copley RCB, Gordon L, Grandi P, Gray JRJ, Harrison LA, Hayhow TG, Lindon M, Messenger C, Michon AM, Mitchell D, Preston A, Prinjha RK, Rioja I, Taylor S, Wall ID, Watson RJ, Woolven JM, Demont EH. The Optimization of a Novel, Weak Bromo and Extra Terminal Domain (BET) Bromodomain Fragment Ligand to a Potent and Selective Second Bromodomain (BD2) Inhibitor. J Med Chem. 2020 Sep 10;63(17):9093-9126. doi: 10.1021/acs.jmedchem.0c00796. Epub 2020 Aug 30. PMID: 32702236. 2. Gilan O, Rioja I, Knezevic K, Bell MJ, Yeung MM, Harker NR, Lam EYN, Chung CW, Bamborough P, Petretich M, Urh M, Atkinson SJ, Bassil AK, Roberts EJ, Vassiliadis D, Burr ML, Preston AGS, Wellaway C, Werner T, Gray JR, Michon AM, Gobbetti T, Kumar V, Soden PE, Haynes A, Vappiani J, Tough DF, Taylor S, Dawson SJ, Bantscheff M, Lindon M, Drewes G, Demont EH, Daniels DL, Grandi P, Prinjha RK, Dawson MA. Selective targeting of BD1 and BD2 of the BET proteins in cancer and immunoinflammation. Science. 2020 Apr 24;368(6489):387-394. doi: 10.1126/science.aaz8455. Epub 2020 Mar 19. PMID: 32193360; PMCID: PMC7610820. |
| In vitro protocol: | 1. Seal JT, Atkinson SJ, Aylott H, Bamborough P, Chung CW, Copley RCB, Gordon L, Grandi P, Gray JRJ, Harrison LA, Hayhow TG, Lindon M, Messenger C, Michon AM, Mitchell D, Preston A, Prinjha RK, Rioja I, Taylor S, Wall ID, Watson RJ, Woolven JM, Demont EH. The Optimization of a Novel, Weak Bromo and Extra Terminal Domain (BET) Bromodomain Fragment Ligand to a Potent and Selective Second Bromodomain (BD2) Inhibitor. J Med Chem. 2020 Sep 10;63(17):9093-9126. doi: 10.1021/acs.jmedchem.0c00796. Epub 2020 Aug 30. PMID: 32702236. |
| In vivo protocol: | 1. Gilan O, Rioja I, Knezevic K, Bell MJ, Yeung MM, Harker NR, Lam EYN, Chung CW, Bamborough P, Petretich M, Urh M, Atkinson SJ, Bassil AK, Roberts EJ, Vassiliadis D, Burr ML, Preston AGS, Wellaway C, Werner T, Gray JR, Michon AM, Gobbetti T, Kumar V, Soden PE, Haynes A, Vappiani J, Tough DF, Taylor S, Dawson SJ, Bantscheff M, Lindon M, Drewes G, Demont EH, Daniels DL, Grandi P, Prinjha RK, Dawson MA. Selective targeting of BD1 and BD2 of the BET proteins in cancer and immunoinflammation. Science. 2020 Apr 24;368(6489):387-394. doi: 10.1126/science.aaz8455. Epub 2020 Mar 19. PMID: 32193360; PMCID: PMC7610820. |
1: Aylott HE, Atkinson SJ, Bamborough P, Bassil A, Chung CW, Gordon L, Grandi P, Gray JRJ, Harrison LA, Hayhow TG, Messenger C, Mitchell D, Phillipou A, Preston A, Prinjha RK, Rianjongdee F, Rioja I, Seal JT, Wall ID, Watson RJ, Woolven JM, Demont EH. Template-Hopping Approach Leads to Potent, Selective, and Highly Soluble Bromo and Extraterminal Domain (BET) Second Bromodomain (BD2) Inhibitors. J Med Chem. 2021 Mar 25;64(6):3249-3281. doi: 10.1021/acs.jmedchem.0c02156. Epub 2021 Mar 4. PMID: 33662213.
2: Seal JT, Atkinson SJ, Aylott H, Bamborough P, Chung CW, Copley RCB, Gordon L, Grandi P, Gray JRJ, Harrison LA, Hayhow TG, Lindon M, Messenger C, Michon AM, Mitchell D, Preston A, Prinjha RK, Rioja I, Taylor S, Wall ID, Watson RJ, Woolven JM, Demont EH. The Optimization of a Novel, Weak Bromo and Extra Terminal Domain (BET) Bromodomain Fragment Ligand to a Potent and Selective Second Bromodomain (BD2) Inhibitor. J Med Chem. 2020 Sep 10;63(17):9093-9126. doi: 10.1021/acs.jmedchem.0c00796. Epub 2020 Aug 30. PMID: 32702236.
