Target Information

Target General Infomation
Target ID
T40016
Former ID
TTDS00283
Target Name
Glucocorticoid receptor
Gene Name
NR3C1
Synonyms
Alpha-A; GR; NR3C1
Target Type
Successful
Disease Asthma; Non-infectious rhinitis [ICD9: 472.0, 477, 493; ICD10: J00, J30, J31.0, J45]
Asthma; Chronic obstructive pulmonary disease [ICD9: 490-492, 493, 494-496; ICD10: J40-J44, J47, J45]
Ataxia telangiectasia [ICD10: G11.3]
Allergic rhinitis [ICD9: 472.0, 477, 995.3; ICD10: J00, J30, J31.0, T78.4]
Asthma [ICD10: J45]
Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42]
Atopic dermatitis [ICD9: 691.8, 692.9; ICD10: L00-L99]
Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47]
Chronic obstructive pulmonary disease; Asthma [ICD9: 490-492, 493, 494-496; ICD10: J40-J44, J47, J45]
Corticosteroid-responsive inflammation [ICD code not available]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Cushing's disease [ICD9: 255; ICD10: E24.0]
Depression [ICD9: 311; ICD10: F30-F39]
Dermatitis [ICD9: 692.9; ICD10: L20-L30]
Dermatological disease [ICD10: L00-L99]
Duchenne muscular dystrophy [ICD10: G71.0]
Eczema [ICD10: L20-L30]
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25]
Inflammation [ICD10: E08-E13, E10.2, E11, E11.2, E13.2, I73.9, I80-I82, N00-N29, G89]
Multiple scierosis [ICD9: 340; ICD10: G35]
Ocular disease [ICD10: H00-H59]
Otitis externa [ICD10: H60]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Rhinitis [ICD9: 472.0, 477; ICD10: J00, J30, J31.0]
Severe mood disorders [ICD9: 296; ICD10: F30-F39]
Skin allergies [ICD9: 995.3; ICD10: T78.4]
Spinal cord injury [ICD10: S14, S24, S34]
Xerophthalmia [ICD10: E50.6-E50.7]
Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
BioChemical Class
Zinc-finger
Target Validation
T40016
UniProt ID
P04150
Sequence
MDSKESLTPGREENPSSVLAQERGDVMDFYKTLRGGATVKVSASSPSLAVASQSDSKQRR
LLVDFPKGSVSNAQQPDLSKAVSLSMGLYMGETETKVMGNDLGFPQQGQISLSSGETDLK
LLEESIANLNRSTSVPENPKSSASTAVSAAPTEKEFPKTHSDVSSEQQHLKGQTGTNGGN
VKLYTTDQSTFDILQDLEFSSGSPGKETNESPWRSDLLIDENCLLSPLAGEDDSFLLEGN
SNEDCKPLILPDTKPKIKDNGDLVLSSPSNVTLPQVKTEKEDFIELCTPGVIKQEKLGTV
YCQASFPGANIIGNKMSAISVHGVSTSGGQMYHYDMNTASLSQQQDQKPIFNVIPPIPVG
SENWNRCQGSGDDNLTSLGTLNFPGRTVFSNGYSSPSMRPDVSSPPSSSSTATTGPPPKL
CLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRYRK
CLQAGMNLEARKTKKKIKGIQQATTGVSQETSENPGNKTIVPATLPQLTPTLVSLLEVIE
PEVLYAGYDSSVPDSTWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDDQMTLLQYSW
MFLMAFALGWRSYRQSSANLLCFAPDLIINEQRMTLPCMYDQCKHMLYVSSELHRLQVSY
EEYLCMKTLLLLSSVPKDGLKSQELFDEIRMTYIKELGKAIVKREGNSSQNWQRFYQLTK
LLDSMHEVVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK
Structure
1M2Z; 1NHZ; 1P93; 3BQD; 3CLD; 3E7C; 3H52; 3K22; 3K23; 4CSJ; 4HN5;4HN6; 4LSJ; 4MDD; 4P6W; 4P6X; 1M2Z; 1NHZ; 1P93; 3BQD; 3CLD; 3E7C; 3H52; 3K22; 3K23; 4CSJ; 4HN5; 4HN6; 4LSJ; 4MDD; 4P6W; 4P6X
Drugs and Mode of Action
Drug(s) Betamethasone Drug Info Approved Inflammatory disease [538521], [542068]
Betamethasone Benzoate Drug Info Approved Inflammation [551871]
Betamethasone Valerate Drug Info Approved Dermatological disease [551871]
Budesonide Drug Info Approved Asthma; Non-infectious rhinitis [536361], [542457]
Deflazacort Drug Info Approved Duchenne muscular dystrophy [524244], [551871], [889446]
Dexamethasone Drug Info Approved Rheumatoid arthritis [536737], [540387]
Dexamethasone sodium phosphate Drug Info Approved Ataxia telangiectasia [549193]
Flunisolide Drug Info Approved Allergic rhinitis [538285], [542082]
Fluocinolone Acetonide Drug Info Approved Inflammatory disease [538524], [542083]
Fluorometholone Drug Info Approved Corticosteroid-responsive inflammation [551871]
Fluticasone Drug Info Approved Allergic rhinitis [551871]
GW685698X Drug Info Approved Chronic obstructive pulmonary disease; Asthma [522134], [551873]
Hydrocortamate Drug Info Approved Inflammatory disease [538430]
Hydrocortisone Drug Info Approved Inflammatory disease [536361], [539893]
Meprednisone Drug Info Approved Chronic obstructive pulmonary disease [551871]
Methylprednisolone Acetate Drug Info Approved Cancer [551871]
Mifepristone Drug Info Approved Cushing's disease [525064], [539846], [551871]
Mometasone Drug Info Approved Skin allergies [536361]
Prednisolone Drug Info Approved Cancer [551871]
Prednisone Drug Info Approved Inflammatory disease [536737], [542102]
Triamcinolone Drug Info Approved Allergic rhinitis [551871]
FST-201 Drug Info Phase 3 Otitis externa [522739]
Mapracorat Drug Info Phase 3 Ocular disease [523362], [543227]
Prednisolone Drug Info Phase 3 Multiple scierosis [525302], [539891]
870086 (topical, atopic dermatitis), GlaxoSmithKline Drug Info Phase 2 Atopic dermatitis [522149], [523364]
DE-110 Drug Info Phase 2 Xerophthalmia [523248]
ETIPREDNOL DICLOACETATE Drug Info Phase 2 Rhinitis [521510]
GW-870086-X Drug Info Phase 2 Asthma [522149], [523364]
LAS-41002 Drug Info Phase 2 Eczema [523032]
ORG 34517/34850 Drug Info Phase 2 Severe mood disorders [536580]
ORG-34517 Drug Info Phase 2 Depression [521717]
TPI-1020 Drug Info Phase 2 Chronic obstructive pulmonary disease [522042]
NCX-1015 Drug Info Phase 1 Rheumatoid arthritis [526716]
AZD-5423 Drug Info Discontinued in Phase 2 Asthma; Chronic obstructive pulmonary disease [549011]
GSK870086 Drug Info Discontinued in Phase 2 Asthma [548295]
NM-135 Drug Info Discontinued in Phase 2 Dermatitis [546950]
WC-3027 Drug Info Discontinued in Phase 2 Chronic obstructive pulmonary disease [548039]
PF-251802 Drug Info Discontinued in Phase 1 Rheumatoid arthritis [548806]
Org-34116 Drug Info Terminated Anxiety disorder [546942]
Methylprednisolone Acetate Drug Info Investigative Spinal cord injury [542093]
Agonist 870086 (topical, atopic dermatitis), GlaxoSmithKline Drug Info [532254]
AZD-5423 Drug Info [533056]
Betamethasone Drug Info [536246]
DE-110 Drug Info [549039]
Dexamethasone Drug Info [537240], [537639]
Dexamethasone sodium phosphate Drug Info [532454]
Flunisolide Drug Info [537122]
FST-201 Drug Info [530380]
GW-870086-X Drug Info [532254]
GW685698X Drug Info [550963]
Mapracorat Drug Info [530111]
Mometasone Drug Info [535655]
PF-251802 Drug Info [550632]
Prednisone Drug Info [537958]
WC-3027 Drug Info [548040]
Inhibitor B-Octylglucoside Drug Info [551393]
Hexane-1,6-Diol Drug Info [551393]
ZK-230211 Drug Info [525950]
Modulator Betamethasone Benzoate Drug Info [556264]
Betamethasone Valerate Drug Info [556264]
Deflazacort Drug Info [556264]
ETIPREDNOL DICLOACETATE Drug Info
Fluocinolone Acetonide Drug Info [556264]
GSK870086 Drug Info [550860]
Hydrocortamate Drug Info [556264]
Hydrocortisone Drug Info [556264]
LAS-41002 Drug Info [544252]
Meprednisone Drug Info [556264]
Methylprednisolone Acetate Drug Info [556264]
Mifepristone Drug Info [528847]
NCX-1015 Drug Info [526716]
NM-135 Drug Info [534820]
Prednisolone Drug Info [525912]
Triamcinolone Drug Info [556264]
Antagonist Budesonide Drug Info [535660], [537013]
Fluticasone Drug Info [535660], [536736]
ORG 34517/34850 Drug Info [536580]
Org-34116 Drug Info [526476]
ORG-34517 Drug Info [529897]
TPI-1020 Drug Info [531896]
Binder Fluorometholone Drug Info [535767]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
DRM DRM Info
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
NetPath Pathway IL2 Signaling Pathway
TCR Signaling Pathway
Pathway Interaction Database Regulation of nuclear SMAD2/3 signaling
Signaling events mediated by HDAC Class II
FOXA2 and FOXA3 transcription factor networks
Glucocorticoid receptor regulatory network
Regulation of Androgen receptor activity
AP-1 transcription factor network
Reactome CLOCK,NPAS2 activates circadian gene expression
WikiPathways Serotonin Receptor 4/6/7 and NR3C Signaling
SIDS Susceptibility Pathways
Nuclear Receptors Meta-Pathway
Endoderm Differentiation
Cytodifferentiation (Part 3 of 3)
Adipogenesis
Circadian Clock
Nuclear Receptors
References
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Ref 521717ClinicalTrials.gov (NCT00212797) A Study to Determine the Efficacy and Safety of 2 Doses of Org 34517 as Adjunctive Therapy in Subjects With Psychotic Major Depression (28130)(P05845). U.S. National Institutes of Health.
Ref 522042ClinicalTrials.gov (NCT00483743) Safety, Tolerability and PD Activity of Inhaled TPI 1020 Versus Inhaled Budesonide in COPD Patients. U.S. National Institutes of Health.
Ref 522134ClinicalTrials.gov (NCT00539006) Comparator Study Evaluating Patient Preference Of FFNS vs. FPNS. U.S. National Institutes of Health.
Ref 522149ClinicalTrials.gov (NCT00549497) A Randomized Study Evaluating Steroid Hormone Levels, Safety And Tolerability Of GW870086X In Healthy Volunteers. U.S. National Institutes of Health.
Ref 522739ClinicalTrials.gov (NCT00945646) FST-201 In The Treatment of Acute Fungal Otitis Externa. U.S. National Institutes of Health.
Ref 523032ClinicalTrials.gov (NCT01119313) Study to Investigate Skin Conditions and Patient Assessment of LAS 41002 in the Treatment of Atopic Eczema. U.S. National Institutes of Health.
Ref 523248ClinicalTrials.gov (NCT01239069) Safety and Efficacy Study of DE-110 Ophthalmic Suspension for the Treatment of Dry Eye Disease. U.S. National Institutes of Health.
Ref 523362ClinicalTrials.gov (NCT01298752) Mapracorat Ophthalmic Suspension, 3% for the Treatment of Ocular Inflammation Following Cataract Surgery. U.S. National Institutes of Health.
Ref 523364ClinicalTrials.gov (NCT01299610) A Study to Test the Effect of 2 Different Doses of Topical GW870086X on Atopic Dermatitis Also Including a Postive Control and a Placebo. U.S. National Institutes of Health.
Ref 524244ClinicalTrials.gov (NCT01817322) Kidney Graft Function Under the Immunosuppression Strategies. U.S. National Institutes of Health.
Ref 525064ClinicalTrials.gov (NCT02342002) Mifepristone and Misoprostol Versus Misoprostol Alone for Missed Abortion: A Randomized-controlled Trial. U.S. National Institutes of Health.
Ref 525302ClinicalTrials.gov (NCT02534896) To Evaluate The Efficacy And Safety Of Intravenous Pegylated Liposomal Prednisolone Sodium Phosphate (Nanocort) Compared With Intramuscular Injection Of Methylprednisolone Acetate In Subjects With Active Rheumatoid Arthritis.
Ref 526716Glucocorticoid receptor nitration leads to enhanced anti-inflammatory effects of novel steroid ligands. J Immunol. 2003 Sep 15;171(6):3245-52.
Ref 536361Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
Ref 536580Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2.
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Ref 538430FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 010554.
Ref 538521FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019137.
Ref 538524FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019452.
Ref 539846(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2805).
Ref 539891(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2866).
Ref 539893(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2868).
Ref 540387(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3447).
Ref 542068(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7061).
Ref 542082(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7076).
Ref 542083(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7077).
Ref 542093(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7088).
Ref 542102(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7096).
Ref 542457(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7434).
Ref 543227(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8643).
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Ref 546950Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011462)
Ref 548039Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021444)
Ref 548295Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024246)
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Ref 549011Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031497)
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Ref 551873Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 889446Drugs@FDA (Edaravone)
Ref 525912Aldosterone (mineralocorticoid) equivalent to prednisolone (glucocorticoid) in reversing hearing loss in MRL/MpJ-Fas1pr autoimmune mice. Laryngoscope. 2000 Nov;110(11):1902-6.
Ref 525950J Med Chem. 2000 Dec 28;43(26):5010-6.Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist.
Ref 526476Blockade of glucocorticoid receptors with ORG 34116 does not normalize stress-induced symptoms in male tree shrews. Eur J Pharmacol. 2002 Dec 20;457(2-3):207-16.
Ref 526716Glucocorticoid receptor nitration leads to enhanced anti-inflammatory effects of novel steroid ligands. J Immunol. 2003 Sep 15;171(6):3245-52.
Ref 528847The glucocorticoid agonist activities of mifepristone (RU486) and progesterone are dependent on glucocorticoid receptor levels but not on EC50 values. Steroids. 2007 Jun;72(6-7):600-8. Epub 2007 Apr7.
Ref 529897Differential effects of the new glucocorticoid receptor antagonist ORG 34517 and RU486 (mifepristone) on glucocorticoid receptor nuclear translocation in the AtT20 cell line. Ann N Y Acad Sci. 2008 Dec;1148:536-41.
Ref 530111Characterization of ZK 245186, a novel, selective glucocorticoid receptor agonist for the topical treatment of inflammatory skin diseases. Br J Pharmacol. 2009 Oct;158(4):1088-103.
Ref 530380A combination povidone-iodine 0.4%/dexamethasone 0.1% ophthalmic suspension in the treatment of adenoviral conjunctivitis. Adv Ther. 2009 Aug;26(8):776-83.
Ref 531896Bronchoprotection in conscious guinea pigs by budesonide and the NO-donating analogue, TPI 1020, alone and combined with tiotropium or formoterol. Br J Pharmacol. 2012 Oct;167(3):515-26.
Ref 532254Unique response profile of trabecular meshwork cells to the novel selective glucocorticoid receptor agonist, GW870086X. Invest Ophthalmol Vis Sci. 2013 Mar 1;54(3):2100-7.
Ref 532454Dexamethasone rapidly increases GABA release in the dorsal motor nucleus of the vagus via retrograde messenger-mediated enhancement of TRPV1 activity. PLoS One. 2013 Jul 30;8(7):e70505.
Ref 533056A nonsteroidal glucocorticoid receptor agonist inhibits allergen-induced late asthmatic responses. Am J Respir Crit Care Med. 2015 Jan 15;191(2):161-7.
Ref 534820Local anti-inflammatory activity and systemic side effects of NM-135, a new prodrug glucocorticoid, in an experimental inflammatory rat model. Jpn J Pharmacol. 1998 Dec;78(4):505-9.
Ref 535655Mometasone furoate is a less specific glucocorticoid than fluticasone propionate. Eur Respir J. 2002 Dec;20(6):1386-92.
Ref 535660Knockouts model the 100 best-selling drugs--will they model the next 100? Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
Ref 535767Loteprednol etabonate: a soft steroid for the treatment of allergic diseases of the airways. Drugs Today (Barc). 2000 May;36(5):313-20.
Ref 536246The cannabinoid CB2 receptor inverse agonist JTE-907 suppresses spontaneous itch-associated responses of NC mice, a model of atopic dermatitis. Eur J Pharmacol. 2006 Aug 7;542(1-3):179-83. Epub 2006Jun 2.
Ref 536580Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2.
Ref 536736Fluticasone furoate nasal spray in allergic rhinitis. Drugs Today (Barc). 2008 Apr;44(4):251-60.
Ref 537013PXR-mediated induction of human CYP3A4 and mouse Cyp3a11 by the glucocorticoid budesonide. Eur J Pharm Sci. 2009 Mar 2;36(4-5):565-71. Epub 2008 Dec 24.
Ref 537122The glucocorticoid receptor heterocomplex gene STIP1 is associated with improved lung function in asthmatic subjects treated with inhaled corticosteroids. J Allergy Clin Immunol. 2009 Jun;123(6):1376-83.e7. Epub 2009 Feb 28.
Ref 537240Interaction between the glucocorticoid and erythropoietin receptors in human erythroid cells. Exp Hematol. 2009 May;37(5):559-72.
Ref 537639Functional mineralocorticoid receptor (MR) gene variation influences the cortisol awakening response after dexamethasone. Psychoneuroendocrinology. 2009 Aug 6.
Ref 537958Cytochromes P450 (CYP) in the Poeciliopsis lucida hepatocellular carcinoma cell line (PLHC-1): dose- and time-dependent glucocorticoid potentiation of CYP1A induction without induction of CYP3A. ArchBiochem Biophys. 1996 May 1;329(1):113-22.
Ref 544252Barrier-Restoring Therapies in Atopic Dermatitis: Current Approaches and Future Perspectives. Dermatol Res Pract. 2012; 2012: 923134.
Ref 548040Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021444)
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Ref 550860CN patent application no. 102388025, Pyrimidopyridazine derivatives useful as p38 mapk inhibitors.
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