1276121-88-0
1276121-88-0 structure
- Name: PF 3644022
- Chemical Name: (10R)-10-Methyl-3-(6-methyl-3-pyridinyl)-9,10,11,12-tetrahydro-8H -[1,4]diazepino[5',6':4,5]thieno[3,2-f]quinolin-8-one
- CAS Number: 1276121-88-0
- Molecular Formula: C21H18N4OS
- Molecular Weight: 374.45900
- Catalog: Signaling Pathways MAPK/ERK Pathway MAPKAPK2 (MK2)
- Create Date: 2017-09-13 18:23:44
- Modify Date: 2024-04-03 15:45:52
-
PF-3644022 is a potent, selective, orally active and ATP-competitive MAPKAPK2 (MK2) inhibitor with an IC50 of 5.2 nM and a Ki of 3 nM. PF-3644022 also inhibits MK3 and p38 regulated/activated kinase (PRAK) with IC50s of 53 nM and 5.0 nM, respectively. PF-3644022 potently inhibits TNFα production and has anti-inflammatory effect[1].
| Name | (10R)-10-Methyl-3-(6-methyl-3-pyridinyl)-9,10,11,12-tetrahydro-8H -[1,4]diazepino[5',6':4,5]thieno[3,2-f]quinolin-8-one |
|---|---|
| Synonyms | 8-Aminoadenine |
| Description | PF-3644022 is a potent, selective, orally active and ATP-competitive MAPKAPK2 (MK2) inhibitor with an IC50 of 5.2 nM and a Ki of 3 nM. PF-3644022 also inhibits MK3 and p38 regulated/activated kinase (PRAK) with IC50s of 53 nM and 5.0 nM, respectively. PF-3644022 potently inhibits TNFα production and has anti-inflammatory effect[1]. |
|---|---|
| Related Catalog | |
| Target |
IC50: 5.2 nM (MK2), 5.0 nM (PRAK) and 53 nM (MK3)[1]. Ki: 3 nM (MK2)[1] |
| In Vitro | The inhibitory activity of PF-3644022 against other MAPKAP kinase family members is evaluated. Other than MNK2 with an IC50 of 148 nM, other family members are largely not inhibited, showing at least several hundred-fold selectivity versus MK2[1]. In the human U937 monocytic cell line or peripheral blood mononuclear cells, PF-3644022 potently inhibits TNFα production with similar activity (IC50 of 160 nM). PF-3644022 blocks TNFα and IL-6 production in LPS-stimulated human whole blood with IC50 values of 1.6 and 10.3 μM, respectively. Inhibition of TNFα in U937 cells and blood correlates closely with inhibition of phospho-heat shock protein 27, a target biomarker of MK2 activity[1]. |
| In Vivo | PF-3644022 (3-100 mg/kg; oral gavage; twice a day; for 12 days; Lewis rats) treatment shows dose-dependent inhibition of chronic paw swelling measured on day 21 after 12 days of oral dosing, with ED50 value of 20 mg/kg[1]. Animal Model: Female Lewis rats (125-140 g) injected with streptococcal cell wall[1] Dosage: 3 mg/kg, 10 mg/kg, 30 mg/kg, 50 mg/kg, 100 mg/kg Administration: Oral gavage; twice a day; for 12 days Result: Showed dose-dependent inhibition of chronic paw swelling measured on day 21 after 12 days of oral dosing. |
| References |
| Molecular Formula | C21H18N4OS |
|---|---|
| Molecular Weight | 374.45900 |
| Exact Mass | 374.12000 |
| PSA | 98.64000 |
| LogP | 4.51210 |
| Hazard Codes | Xi |
|---|