ADEZMAPIMOD

Details

Stereochemistry	RACEMIC
Molecular Formula	C21H16FN3OS
Molecular Weight	377.435
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[S+]([O-])C1=CC=C(C=C1)C2=NC(=C(N2)C3=CC=NC=C3)C4=CC=C(F)C=C4

InChI

InChIKey=CDMGBJANTYXAIV-UHFFFAOYSA-N

InChI=1S/C21H16FN3OS/c1-27(26)18-8-4-16(5-9-18)21-24-19(14-2-6-17(22)7-3-14)20(25-21)15-10-12-23-13-11-15/h2-13H,1H3,(H,24,25)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10702313 | http://adisinsight.springer.com/drugs/800007147
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/10960075 https://www.ncbi.nlm.nih.gov/pubmed/22170404

SB-203580 was originally prepared as inflammatory cytokine synthesis inhibitor that subsequently was found to be selective inhibitor of p38 MAP kinase. SB-203580 is a p38 MAPK inhibitor with IC50 of 0.3-0.5 uM in THP-1 cells, 10-fold less sensitive to SAPK3(106T) and SAPK4(106T) and blocks PKB phosphorylation with IC50 of 3-5 uM. SB203580 induces autophagy in human hepatocellular carcinoma (HCC) cells. Development of SB-203580 for cancer; postmenopausal osteoporosis; rheumatoid arthritis; septic shock has been discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase RAF 10 Target ID: CHEMBL1906 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20536832	Inhibitor 8297	2.0 µM [IC50]
MAP kinase p38 alpha 35 Target ID: CHEMBL260 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11354358 \| https://www.ncbi.nlm.nih.gov/pubmed/?term=12039561	Inhibitor 8297	48.0 nM [IC50]
MAP kinase p38 5 Target ID: CHEMBL2094115 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12061876	Inhibitor 8297	37.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Cancer 592 Sources: http://adisinsight.springer.com/drugs/800007147	Primary	Preclinical	Unknown Approved Use Unknown
Rheumatoid arthritis 316 Sources: http://adisinsight.springer.com/drugs/800007147	Primary	Preclinical	Unknown Approved Use Unknown
Postmenopausal osteoporosis 59 Sources: http://adisinsight.springer.com/drugs/800007147	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Transcriptional induction of MKP-1 in response to stress is associated with histone H3 phosphorylation-acetylation.	2001 Dec	11689710
Activation of beta(2)-adrenoceptor prevents shiga toxin 2-induced TNF-alpha gene transcription.	2001 Nov	11675405
Focal adhesion features during myofibroblastic differentiation are controlled by intracellular and extracellular factors.	2001 Sep	11591817
Pathways of induction of peroxiredoxin I expression in osteoblasts: roles of p38 mitogen-activated protein kinase and protein kinase C.	2002 Apr 5	11796722
High glucose stimulates angiotensinogen gene expression via reactive oxygen species generation in rat kidney proximal tubular cells.	2002 Aug	12130563
Lipoteichoic acid-induced cyclooxygenase-2 expression requires activations of p44/42 and p38 mitogen-activated protein kinase signal pathways.	2002 Aug 16	12176102
Fibroblast growth factor (FGF)-23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway.	2002 Aug 2	12032146
Antioxidants induce different phenotypes by a distinct modulation of signal transduction.	2002 Dec 18	12482581
Involvement of p38 mitogen-activated protein kinase in the cell growth inhibition by sodium arsenite.	2002 Jan	11807808
Role of mitogen-activated protein kinase pathway in acetylcholine-mediated in vitro relaxation of rat pulmonary artery.	2002 Jan 2	11755166
Pyridinylimidazole p38 mitogen-activated protein kinase inhibitors block intracellular Toxoplasma gondii replication.	2002 Jul	12076626
Alcohol activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells.	2002 Jul	12065697
Activation of presynaptic P2X7-like receptors depresses mossy fiber-CA3 synaptic transmission through p38 mitogen-activated protein kinase.	2002 Jul 15	12122056
Cellular stresses profoundly inhibit protein synthesis and modulate the states of phosphorylation of multiple translation factors.	2002 Jun	12071973
IL-17 stimulates inflammatory responses via NF-kappaB and MAP kinase pathways in human colonic myofibroblasts.	2002 Jun	12016129
Regulation of cyclooxygenase-2 expression by phospholipase D in human amnion-derived WISH cells.	2002 Mar	11854442
Involvement of p38 mitogen-activated protein kinase in PLL-AGE-induced cyclooxgenase-2 expression.	2002 Mar 8	11909605
Acrolein activates mitogen-activated protein kinase signal transduction pathways in rat vascular smooth muscle cells.	2002 Nov	12487375
Activation of Rac1 and the p38 mitogen-activated protein kinase pathway in response to arsenic trioxide.	2002 Nov 22	12239215
Vomitoxin-induced cyclooxygenase-2 gene expression in macrophages mediated by activation of ERK and p38 but not JNK mitogen-activated protein kinases.	2002 Oct	12377986
Tumor promoter arsenite stimulates histone H3 phosphoacetylation of proto-oncogenes c-fos and c-jun chromatin in human diploid fibroblasts.	2003 Apr 11	12547826
Involvement of p38 mitogen-activated protein kinase in heat shock protein 27 induction in human neutrophils.	2003 Apr 18	12694807
Phosphorylation of initiation factor 4E is resistant to SB203580 in cells expressing a drug-resistant mutant of stress-activated protein kinase 2a/p38.	2003 Aug	12781867
Induction of glia maturation factor-beta in proximal tubular cells leads to vulnerability to oxidative injury through the p38 pathway and changes in antioxidant enzyme activities.	2003 Aug 29	12791701
Tumor necrosis factor-alpha and troglitazone regulate plasminogen activator inhibitor type 1 production through extracellular signal-regulated kinase- and nuclear factor-kappaB-dependent pathways in cultured human umbilical vein endothelial cells.	2003 Dec	14534369
Phenotypic switching of VEGF and collagen XVIII during hypoxia in head and neck squamous carcinoma cells.	2003 Dec	13679210
Cadmium induces nuclear export of Bach1, a transcriptional repressor of heme oxygenase-1 gene.	2003 Dec 5	14504288
Critical role of c-Jun N-terminal protein kinase activation in troglitazone-induced apoptosis of human HepG2 hepatoma cells.	2003 Feb	12527812
Heat shock and Cd2+ exposure regulate PML and Daxx release from ND10 by independent mechanisms that modify the induction of heat-shock proteins 70 and 25 differently.	2003 Feb 1	12508112
Amphiregulin is a potent mitogen for the vascular smooth muscle cell line, A7r5.	2003 Feb 21	12589827
Evidence for a role of p38 kinase in hypoxia-inducible factor 1-independent induction of vascular endothelial growth factor expression by sodium arsenite.	2003 Feb 28	12482858
Suppression of tumor necrosis factor-alpha by beta2-adrenoceptor activation: role of mitogen-activated protein kinases in renal mesangial cells.	2003 Jan	12608646
Inhibition of p38 mitogen-activated protein kinase blocks activation of rat pancreatic stellate cells.	2003 Jan	12490569
Gadolinium chloride reverses dimethylnitrosamine (DMN)-induced rat liver fibrosis with increased matrix metalloproteinases (MMPs) of Kupffer cells.	2003 Jan 10	12493575
Mechanisms of endotoxin tolerance in human intestinal microvascular endothelial cells.	2003 Jun 15	12794122
Potentiation of lipopolysaccharide-inducible cyclooxygenase 2 expression by C2-ceramide via c-Jun N-terminal kinase-mediated activation of CCAAT/enhancer binding protein beta in macrophages.	2003 Mar	12606757
Effect of the lipid peroxidation product acrolein on tau phosphorylation in neural cells.	2003 Mar 15	12605413
Immediate-early gene induction by the stresses anisomycin and arsenite in human osteosarcoma cells involves MAPK cascade signaling to Elk-1, CREB and SRF.	2003 Mar 27	12660819
Vanadium-induced HB-EGF expression in human lung fibroblasts is oxidant dependent and requires MAP kinases.	2003 May	12676768
Selective roles for Toll-like receptor (TLR)2 and TLR4 in the regulation of neutrophil activation and life span.	2003 May 15	12734376
Arsenite stimulated glucose transport in 3T3-L1 adipocytes involves both Glut4 translocation and p38 MAPK activity.	2003 Oct	14511371
Adenosine-induced IL-6 expression in pituitary folliculostellate cells is mediated via A2b adenosine receptors coupled to PKC and p38 MAPK.	2003 Oct	14504137
Lipopolysaccharide-induced dopaminergic cell death in rat midbrain slice cultures: role of inducible nitric oxide synthase and protection by indomethacin.	2003 Sep	12911628
Regulation of toll-like receptor 2 and 4 gene expression in murine alveolar macrophages.	2003 Sep	12888452
Air pollution particles produce airway wall remodeling in rat tracheal explants.	2003 Sep	12649123
Phosphatidylinositol 3-kinase in angiotensin II-induced hypertrophy of vascular smooth muscle cells.	2003 Sep 30	14555183
Co-treatment with dexamethasone and octanoate induces adipogenesis in 3T3-L1 cells.	2004	14984747
Selenium attenuates lipopolysaccharide-induced oxidative stress responses through modulation of p38 MAPK and NF-kappaB signaling pathways.	2004 Feb	14734799
PDTC, metal chelating compound, induces G1 phase cell cycle arrest in vascular smooth muscle cells through inducing p21Cip1 expression: involvement of p38 mitogen activated protein kinase.	2004 Feb	14603533
Endothelin-1 promotes phosphorylation of CREB transcription factor in primary cultures of neonatal rat cardiac myocytes: implications for the regulation of c-jun expression.	2004 Feb 2	14741741

Patents

Sample Use Guides

In Vivo Use Guide

four intraperitoneal injections of 5 mg/kg

Route of Administration: Intraperitoneal

In Vitro Use Guide

After treatment with SB-203580 (15 uM/L) 24 h and 48 h, the early and late apoptosis of MCF-7/Adr cells expressing the phosphorylated p38MAPK protein was (25.36 +/- 1.17)% and (38.21 +/- 1.25)%, respectively

Name

Type

Language

ADEZMAPIMOD

Official Name

English

adezmapimod [INN]

Common Name

English

PYRIDINE, 4-(4-(4-FLUOROPHENYL)-2-(4-(METHYLSULFINYL)PHENYL)-1H-IMIDAZOL-5-YL)-

Systematic Name

English

RAC-4-(5-(4-FLUOROPHENYL)-2-(4-((R)- METHANESULFINYL)PHENYL)-1H-IMIDAZOL-4-YL)PYRIDINE

Systematic Name

English

SB-203580

Code

English

BIRB203580

Code

English

SB203580

Code

English

PB203580

Code

English

BIRB-203580

Code

English

PB-203580

Code

English

RWJ-64809

Code

English

RWJ64809

Code

English

Code System Code Type Description

EPA CompTox

DTXSID2040577