Target Validation Information | |||||
---|---|---|---|---|---|
TTD ID | T65864 | ||||
Target Name | Stress-activated protein kinase 2a (p38 alpha) | ||||
Type of Target |
Clinical trial |
||||
Drug Potency against Target | Dilmapimod | Drug Info | IC50 = 44 nM | [22] | |
(5-amino-1-phenyl-1H-pyrazol-4-yl)phenylmethanone | Drug Info | IC50 = 570 nM | [10] | ||
4-(2-Ethyl-4-m-tolyl-thiazol-5-yl)-pyridine | Drug Info | IC50 = 15 nM | [8] | ||
6-o-tolylquinazolin-2-amine | Drug Info | IC50 = 3903 nM | [13] | ||
BMS-582949 | Drug Info | IC50 = 3.5 nM | [14] | ||
Dihydro-quinolinone | Drug Info | IC50 = 0.74 nM | [20] | ||
GW-788388 | Drug Info | IC50 = 7280 nM | [11] | ||
IN-1130 | Drug Info | IC50 = 4300 nM | [16] | ||
IN-1166 | Drug Info | IC50 = 1030 nM | [16] | ||
ML-3163 | Drug Info | IC50 = 880 nM | [1] | ||
ML-3375 | Drug Info | IC50 = 1200 nM | [3] | ||
ML-3403 | Drug Info | IC50 = 990 nM | [3] | ||
N-(3-(trifluoromethoxy)benzyl)-4-phenoxybenzamide | Drug Info | IC50 = 600 nM | [9] | ||
N-(3-(trifluoromethyl)benzyl)-4-phenoxybenzamide | Drug Info | IC50 = 450 nM | [9] | ||
N-(4-(trifluoromethyl)benzyl)-4-phenoxybenzamide | Drug Info | IC50 = 1400 nM | [9] | ||
N-(4-fluorobenzyl)-N-(pyridin-4-yl)-2-naphthamide | Drug Info | IC50 = 1260 nM | [21] | ||
N-(4-methyl-benzyl)-4-phenoxy-benzamide | Drug Info | IC50 = 1600 nM | [9] | ||
PAMAPIMOD | Drug Info | IC50 = 14 nM | [19] | ||
PD-0166326 | Drug Info | IC50 = 140 nM | [18] | ||
PD-0173956 | Drug Info | IC50 = 50 nM | [18] | ||
PH-797804 | Drug Info | IC50 = 5 nM | [12] | ||
Phenyl-(3-phenyl-1H-indazol-6-yl)-amine | Drug Info | IC50 = 30 nM | [6] | ||
Ro-3201195 | Drug Info | IC50 = 180 nM | [15] | ||
RWJ-68354 | Drug Info | IC50 = 1500 nM | [2] | ||
SB-216995 | Drug Info | IC50 = 160 nM | [20] | ||
SB-218655 | Drug Info | IC50 = 25 nM | [20] | ||
SB-227931 | Drug Info | IC50 = 46 nM | [7] | ||
SB-242235 | Drug Info | IC50 = 130 nM | [17] | ||
Talmapimod | Drug Info | IC50 = 9 nM | [19] | ||
Tyrphostin ag-1478 | Drug Info | IC50 = 560 nM | [5] | ||
ZM-336372 | Drug Info | IC50 = 180 nM | [4] | ||
Action against Disease Model | Losmapimod | Drug Info | Inhibition of p38 mitogen-activated protein kinase improves nitric oxide-mediated vasodilatation and reduces inflammation in hypercholesterolemia. Losmapimod improves nitric oxide-mediated vasodilatation in hypercholesterolemic patients, which is consistent with findings in previous translational animal models. These data support the hypothesis that attenuating the inflammatory milieu by inhibiting p38 MAPK activity improves NO activity, and p38 MAPK is a novel target for patients with cardiovascular disease. | [23] | |
References | |||||
REF 1 | From imidazoles to pyrimidines: new inhibitors of cytokine release. J Med Chem. 2002 Jun 20;45(13):2733-40. | ||||
REF 2 | Imidazopyrimidines, potent inhibitors of p38 MAP kinase. Bioorg Med Chem Lett. 2003 Feb 10;13(3):347-50. | ||||
REF 3 | Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes. J Med Chem. 2003 Jul 17;46(15):3230-44. | ||||
REF 4 | A novel series of p38 MAP kinase inhibitors for the potential treatment of rheumatoid arthritis. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5383-7. | ||||
REF 5 | Novel, potent and selective anilinoquinazoline and anilinopyrimidine inhibitors of p38 MAP kinase. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5389-94. | ||||
REF 6 | Design and synthesis of 6-anilinoindazoles as selective inhibitors of c-Jun N-terminal kinase-3. Bioorg Med Chem Lett. 2005 Nov 15;15(22):5095-9. | ||||
REF 7 | The neuroprotective action of JNK3 inhibitors based on the 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole scaffold. Bioorg Med Chem Lett. 2005 Nov 1;15(21):4666-70. | ||||
REF 8 | Novel inhibitor of p38 MAP kinase as an anti-TNF-alpha drug: discovery of N-[4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (T... J Med Chem. 2005 Sep 22;48(19):5966-79. | ||||
REF 9 | Two classes of p38alpha MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes. Bioorg Med Chem Lett. 2005 Dec 1;15(23):5274-9. | ||||
REF 10 | Discovery of S-[5-amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]-[3-(2,3-dihydroxypropoxy)phenyl]methanone (RO3201195), an orally bioavailable and highl... J Med Chem. 2006 Mar 9;49(5):1562-75. | ||||
REF 11 | Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orall... J Med Chem. 2006 Apr 6;49(7):2210-21. | ||||
REF 12 | Structure-activity relationships of triazolopyridine oxazole p38 inhibitors: identification of candidates for clinical development. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4339-44. | ||||
REF 13 | Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity. J Med Chem. 2006 Sep 21;49(19):5671-86. | ||||
REF 14 | The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)-A potent and efficacious p38alph... Bioorg Med Chem Lett. 2008 Mar 15;18(6):1762-7. | ||||
REF 15 | Microwave-assisted synthesis of 5-aminopyrazol-4-yl ketones and the p38(MAPK) inhibitor RO3201195 for study in Werner syndrome cells. Bioorg Med Chem Lett. 2008 Jul 1;18(13):3745-8. | ||||
REF 16 | Synthesis and biological evaluation of trisubstituted imidazole derivatives as inhibitors of p38alpha mitogen-activated protein kinase. Bioorg Med Chem Lett. 2008 Jul 15;18(14):4006-10. | ||||
REF 17 | Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes. Bioorg Med Chem Lett. 2008 Aug 1;18(15):4433-7. | ||||
REF 18 | Structure-activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6872-6. | ||||
REF 19 | Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders. J Med Chem. 2010 Mar 25;53(6):2345-53. | ||||
REF 20 | In silico search for multi-target anti-inflammatories in Chinese herbs and formulas. Bioorg Med Chem. 2010 Mar 15;18(6):2204-2218. | ||||
REF 21 | Amide-based inhibitors of p38alpha MAP kinase. Part 2: design, synthesis and SAR of potent N-pyrimidyl amides. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2560-3. | ||||
REF 22 | SB 239063, a second-generation p38 mitogen-activated protein kinase inhibitor, reduces brain injury and neurological deficits in cerebral focal ischemia. J Pharmacol Exp Ther. 2001 Feb;296(2):312-21. | ||||
REF 23 | Inhibition of p38 mitogen-activated protein kinase improves nitric oxide-mediated vasodilatation and reduces inflammation in hypercholesterolemia. Circulation. 2011 Feb 8;123(5):515-23. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.