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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 of ADEZMAPIMOD

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
Molecular Formula C21H16FN3OS
Molecular Weight 377.435
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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

CNS Active
4002
Curator's Comment: In mice SB-203580 protects against MPTP-induced dopaminergic neuronal death and motor deficits.

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 2.0 µM [IC50]
Inhibitor
8504
 48.0 nM [IC50]
Inhibitor
8504
 37.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Overexpression of aldehyde dehydrogenase-2 (ALDH2) transgene prevents acetaldehyde-induced cell injury in human umbilical vein endothelial cells: role of ERK and p38 mitogen-activated protein kinase.
2004-03-19
A p38 inhibitor allows to dissociate differentiation and apoptotic processes triggered upon LIF withdrawal in mouse embryonic stem cells.
2004-03
Tamoxifen inhibits cell proliferation via mitogen-activated protein kinase cascades in human ovarian cancer cell lines in a manner not dependent on the expression of estrogen receptor or the sensitivity to cisplatin.
2004-03
Expression of adhesion molecules by sphingosine 1-phosphate and histamine in endothelial cells.
2004-02-20
Endothelin-1 promotes phosphorylation of CREB transcription factor in primary cultures of neonatal rat cardiac myocytes: implications for the regulation of c-jun expression.
2004-02-02
Aspirin-mediated COX-2 transcript stabilization via sustained p38 activation in human intestinal myofibroblasts.
2004-02
Selenium attenuates lipopolysaccharide-induced oxidative stress responses through modulation of p38 MAPK and NF-kappaB signaling pathways.
2004-02
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.
2004-02
Copper-inducible transcription: regulation by metal- and oxidative stress-responsive pathways.
2004-02
12-O-tetradecanoylphorbol-13-acetate may both potentiate and decrease the generation of apoptosis by the antileukemic agent arsenic trioxide in human promonocytic cells. Regulation by extracellular signal-regulated protein kinases and glutathione.
2004-01-30
Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human gastric cancer cells.
2004-01-15
Co-treatment with dexamethasone and octanoate induces adipogenesis in 3T3-L1 cells.
2004
Phorbol ester stimulates the nonhypoxic induction of a novel hypoxia-inducible factor 1alpha isoform: implications for tumor promotion.
2003-12-15
Cadmium induces nuclear export of Bach1, a transcriptional repressor of heme oxygenase-1 gene.
2003-12-05
Transcriptional and posttranscriptional roles for p38 mitogen-activated protein kinase in upregulation of TNF-alpha expression by deoxynivalenol (vomitoxin).
2003-12-01
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.
2003-12
Phenotypic switching of VEGF and collagen XVIII during hypoxia in head and neck squamous carcinoma cells.
2003-12
Arsenite stimulated glucose transport in 3T3-L1 adipocytes involves both Glut4 translocation and p38 MAPK activity.
2003-10
Adenosine-induced IL-6 expression in pituitary folliculostellate cells is mediated via A2b adenosine receptors coupled to PKC and p38 MAPK.
2003-10
Phosphatidylinositol 3-kinase in angiotensin II-induced hypertrophy of vascular smooth muscle cells.
2003-09-30
Lipopolysaccharide-induced dopaminergic cell death in rat midbrain slice cultures: role of inducible nitric oxide synthase and protection by indomethacin.
2003-09
Regulation of toll-like receptor 2 and 4 gene expression in murine alveolar macrophages.
2003-09
Air pollution particles produce airway wall remodeling in rat tracheal explants.
2003-09
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.
2003-08-29
Phosphorylation of initiation factor 4E is resistant to SB203580 in cells expressing a drug-resistant mutant of stress-activated protein kinase 2a/p38.
2003-08
Mechanisms of endotoxin tolerance in human intestinal microvascular endothelial cells.
2003-06-15
Selective roles for Toll-like receptor (TLR)2 and TLR4 in the regulation of neutrophil activation and life span.
2003-05-15
Vanadium-induced HB-EGF expression in human lung fibroblasts is oxidant dependent and requires MAP kinases.
2003-05
Involvement of p38 mitogen-activated protein kinase in heat shock protein 27 induction in human neutrophils.
2003-04-18
Tumor promoter arsenite stimulates histone H3 phosphoacetylation of proto-oncogenes c-fos and c-jun chromatin in human diploid fibroblasts.
2003-04-11
Immediate-early gene induction by the stresses anisomycin and arsenite in human osteosarcoma cells involves MAPK cascade signaling to Elk-1, CREB and SRF.
2003-03-27
Effect of the lipid peroxidation product acrolein on tau phosphorylation in neural cells.
2003-03-15
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.
2003-03
Evidence for a role of p38 kinase in hypoxia-inducible factor 1-independent induction of vascular endothelial growth factor expression by sodium arsenite.
2003-02-28
Amphiregulin is a potent mitogen for the vascular smooth muscle cell line, A7r5.
2003-02-21
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.
2003-02-01
Critical role of c-Jun N-terminal protein kinase activation in troglitazone-induced apoptosis of human HepG2 hepatoma cells.
2003-02
Gadolinium chloride reverses dimethylnitrosamine (DMN)-induced rat liver fibrosis with increased matrix metalloproteinases (MMPs) of Kupffer cells.
2003-01-10
Suppression of tumor necrosis factor-alpha by beta2-adrenoceptor activation: role of mitogen-activated protein kinases in renal mesangial cells.
2003-01
Inhibition of p38 mitogen-activated protein kinase blocks activation of rat pancreatic stellate cells.
2003-01
Antioxidants induce different phenotypes by a distinct modulation of signal transduction.
2002-12-18
Activation of Rac1 and the p38 mitogen-activated protein kinase pathway in response to arsenic trioxide.
2002-11-22
Acrolein activates mitogen-activated protein kinase signal transduction pathways in rat vascular smooth muscle cells.
2002-11
Vomitoxin-induced cyclooxygenase-2 gene expression in macrophages mediated by activation of ERK and p38 but not JNK mitogen-activated protein kinases.
2002-10
Lipoteichoic acid-induced cyclooxygenase-2 expression requires activations of p44/42 and p38 mitogen-activated protein kinase signal pathways.
2002-08-16
High glucose stimulates angiotensinogen gene expression via reactive oxygen species generation in rat kidney proximal tubular cells.
2002-08
Activation of presynaptic P2X7-like receptors depresses mossy fiber-CA3 synaptic transmission through p38 mitogen-activated protein kinase.
2002-07-15
Pyridinylimidazole p38 mitogen-activated protein kinase inhibitors block intracellular Toxoplasma gondii replication.
2002-07
Alcohol activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells.
2002-07
Cellular stresses profoundly inhibit protein synthesis and modulate the states of phosphorylation of multiple translation factors.
2002-06
Patents

Patents

20020028798
8
20040067953
1

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
Substance Class Chemical
Created
by admin
on Mon Mar 31 22:14:14 GMT 2025
Edited
by admin
on Mon Mar 31 22:14:14 GMT 2025
Record UNII
OU13V1EYWQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ADEZMAPIMOD
INN  
Official Name English
BIRB-203580
Preferred 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
PB-203580
Code English
RWJ-64809
Code English
RWJ64809
Code English
Code System Code Type Description
EPA CompTox
DTXSID2040577
Created by admin on Mon Mar 31 22:14:14 GMT 2025 , Edited by admin on Mon Mar 31 22:14:14 GMT 2025
PRIMARY
SMS_ID
300000032272
Created by admin on Mon Mar 31 22:14:14 GMT 2025 , Edited by admin on Mon Mar 31 22:14:14 GMT 2025
PRIMARY
PUBCHEM
176155
Created by admin on Mon Mar 31 22:14:14 GMT 2025 , Edited by admin on Mon Mar 31 22:14:14 GMT 2025
PRIMARY
FDA UNII
OU13V1EYWQ
Created by admin on Mon Mar 31 22:14:14 GMT 2025 , Edited by admin on Mon Mar 31 22:14:14 GMT 2025
PRIMARY
NCI_THESAURUS
C179071
Created by admin on Mon Mar 31 22:14:14 GMT 2025 , Edited by admin on Mon Mar 31 22:14:14 GMT 2025
PRIMARY
WIKIPEDIA
SB-203580
Created by admin on Mon Mar 31 22:14:14 GMT 2025 , Edited by admin on Mon Mar 31 22:14:14 GMT 2025
PRIMARY
CHEBI
90705
Created by admin on Mon Mar 31 22:14:14 GMT 2025 , Edited by admin on Mon Mar 31 22:14:14 GMT 2025
PRIMARY
CAS
152121-47-6
Created by admin on Mon Mar 31 22:14:14 GMT 2025 , Edited by admin on Mon Mar 31 22:14:14 GMT 2025
PRIMARY
INN
11540
Created by admin on Mon Mar 31 22:14:14 GMT 2025 , Edited by admin on Mon Mar 31 22:14:14 GMT 2025
PRIMARY INN
Related Record Type Details
MITOGEN-ACTIVATED PROTEIN KINASE 11
TARGET -> INHIBITOR
Structure of ADEZMAPIMOD, (S)-
ENANTIOMER -> RACEMATE
Structure of ADEZMAPIMOD, (R)-
ENANTIOMER -> RACEMATE
MITOGEN-ACTIVATED PROTEIN KINASE 14
TARGET -> INHIBITOR
Related Record Type Details
Structure of ADEZMAPIMOD
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