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GSK2982772 1622848-92-3
GSK2982772 is a potent and ATP competitive RIP1 inhibitor with an IC50 of 16 nM.
| Cas No. | 1622848-92-3 |
Canonical SMILES | O=C(C1=NC(CC2=CC=CC=C2)=NN1)N[C@H]3COC4=CC=CC=C4N(C)C3=O |
Formula | C20H19N5O3 |
M.Wt | 377.4 |
Storage | Store at -20°C |
Solubility | DMSO : ≥ 100 mg/mL (264.97 mM) |
General tips | Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing. Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month. |
| To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
GSK2982772 shows more than 1,000-fold selectivity for ERK5 over a panel of over 339 kinases at 10 uM. In stimulated cellular systems,GSK2982772 is also able to reduce spontaneous production of cytokines (IL-1β and IL-6) in a concentration-dependent fashion from ulcerative colitis explant tissue in overnight incubations. GSK2982772 produces a weak concentration dependent inhibition of hERG in human embryonic kidney (HEK-293) cells, with an estimated IC50 of 195 uM, and also shows a weak activation of the human Pregnane X receptor (hPXR) with an EC50 of 13 uM[1].
GSK2982772 is dosed orally 15 min prior to TNF and shows 68, 80, and 87% protection from temperature loss over 6 h, at doses of 3, 10, and 50 mg/kg, respectively. In the corresponding TNF/zVAD model, GSK2982772 shows 13, 63, and 93% protection from temperature loss over 3 h. GSK2982772 displays a good free fraction in blood in rats (4.2%), dogs (11%), cynomolgus monkeys (11%), and humans (7.4%). The inhibitor has a good pharmacokinetic profile across both rats and monkeys. GSK2982772 distributes into a range of tissues including the colon, liver, kidney, and heart at concentrations comparable to those of blood. However, GSK2982772 has low brain penetration in rat (4%) despite possessing good cell permeability (21×10-6 cm/s)[1].
References:
[1]. Harris PA, et al. Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases. J Med Chem. 2017 Feb 23;60(4):1247-1261.
For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.