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Drug-Target Interaction

Drug

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PubChem ID:8515
Structure:
Synonyms:
"insolution™ jnk inhibitor ii"
1,9-Pyrazoloanthrone
129-56-6
14,15-diazatetracyclo[7.6.1.0^{2,7}.0^{13,16}]hexadeca-1(15),2(7),3,5,9,11
1pmv
2,6-DIHYDROANTHRA/1,9-CD/PYRAZOL-6-ONE
2H-Dibenzo[cd,g]indazol-6-one
AIDS-220090
AIDS220090
ANTHRA(1,9-cd)PYRAZOL-6(2H)-ONE
Anthra-1,9-pyrazol-6-none
Anthrapyrazolone
Anthra[1,9-cd]pyrazol-6(2H)-one
Anthra[1,9-cd]pyrazol-6(2H)-one & Z-100
BAS 00719687
BCBcMAP01_000053
Bio1_000335
Bio1_000824
Bio1_001313
Bio2_000373
Bio2_000853
BiomolKI2_000072
BiomolKI_000068
BRN 0746890
BSPBio_001066
C.I. 70300
C432165
CBiol_002049
dibenzo[cd,g]indazol-6(2H)-one
dihydroanthrapyrazole compound 4
EINECS 204-955-6
EU-0100473
HSCI1_000136
IDI1_002128
InSolution™ JNK Inhibitor II
JNK Inhibitor II
K00068
KBio2_000406
KBio2_002974
KBio2_005542
KBio3_000771
KBio3_000772
KBioGR_000406
KBioSS_000406
Lopac-S-5567
Lopac0_000473
LS-20607
MLS002153267
NCGC00015958-01
NCGC00025186-01
NCGC00025186-02
NCGC00025186-03
NCGC00025186-04
NCGC00025186-05
NSC 75890
NSC75890
Pyrazolanthrone
Pyrazoleanthrone
QTL1_000077
RH 00237
S5567_SIGMA
SAPK Inhibitor II
SBB000595
SMP2_000240
SMR000015440
SP 600125
SP 600125 & Z-100
SP600125
SR-01000637108-1
TL8000704
Tocris-1496
WLN: T C6665 1A P IV OMNJ
ZINC04335977

Target

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Uniprot ID:CP1A1_HUMAN
Synonyms:
CYPIA1
Cytochrome P450 1A1
P450 form 6
P450-C
P450-P1
EC-Numbers:1.14.14.1
Organism:Homo sapiens
Human
PDB IDs:-

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----
----
----

References:

14570754
The Jun N-terminal kinase inhibitor SP600125 is a ligand and antagonist of the aryl hydrocarbon receptor.. Aby Joiakim; Patricia A Mathieu; Christine Palermo; Thomas A Gasiewicz; John J ReinersJr (2003) Drug metabolism and disposition: the biological fate of chemicals display abstract
Exposure of the immortalized human breast epithelial cell line MCF10A to the Jun N-terminal kinase (JNK) inhibitor anthra[1,9-cd]pyrazol-6(2H)-one (SP600125) suppressed, in a concentration-dependent manner (IC50 is approximately 2 microM), the induction of CYP1A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Cotreatment with SP600125 also suppressed the accumulation of TCDD-induced nuclear aryl hydrocarbon receptor (AhR)-DNA complexes, as assessed by electrophoretic mobility shift assays. Concentrations of SP600125 < or = 50 microM did not transform the AhR into a DNA-binding species when added to rat liver cytosol. However, addition of SP600125 to cytosol just before TCDD addition completely suppressed AhR transformation and DNA binding (IC50 approximately 7 microM). Sucrose gradient analyses using rat liver and murine hepatoma 1c1c7 extracts demonstrated that SP600125 competed with TCDD for binding to the AhR. These results suggest that SP600125 is an AhR ligand and functions as an AhR antagonist at concentrations used to pharmacologically inhibit JNK.
17959153
JNK inhibitor SP600125 is a partial agonist of human aryl hydrocarbon receptor and induces CYP1A1 and CYP1A2 genes in primary human hepatocytes.. Zdenek Dvorak; Radim Vrzal; Pavla Henklova; Petra Jancova; Eva Anzenbacherova; Patrick Maurel; Lucie Svecova; Petr Pavek; Jiri Ehrmann; Roman Havlik; Petr Bednar; Karel Lemr; Jitka Ulrichova (2008) Biochemical pharmacology display abstract
SP600125, a specific inhibitor of c-Jun-N-Terminal kinase (JNK), was reported as a ligand and antagonist of aryl hydrocarbon receptor (AhR) [Joiakim A, Mathieu PA, Palermo C, Gasiewicz TA, Reiners Jr JJ. The Jun N terminal kinase inhibitor SP600125 is a ligand and antagonist of the aryl hydrocarbon receptor. Drug Metab Dispos 2003;31(11):1279-82]. Here we show that SP600125 is not an antagonist but a partial agonist of human AhR. SP600125 significantly induced CYP1A1 and CYP1A2 mRNAs in primary human hepatocytes and CYP1A1 mRNA in human hepatoma cells HepG2. This effect was abolished by resveratrol, an antagonist of AhR. Consistent with the recent report, SP600125 dose-dependently inhibited CYP1A1 and CYP1A2 genes induction by a prototype AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in human hepatocytes. Moreover, SP600125 displayed typical behavior of a partial agonist in HepG2 cells transiently transfected with a reporter plasmid containing two inverted repeats of the dioxin responsive element or with a plasmid containing 5'-flanking region of human CYP1A1 gene. SP600125 transactivated the reporter plasmids with EC(50) of 0.005 and 1.89 microM, respectively. On the other hand, TCDD-dependent transactivation of the reporter plasmids was inhibited by SP600125 with IC(50) values of 1.54 and 2.63 microM, respectively. We also tested, whether the effects of SP600125 are due to metabolism. Using liquid chromatography/mass spectrometry approach, we observed formation of two minor monohydroxylated metabolites of SP600125 in human hepatocytes, human liver microsomes but not in HepG2 cells. These data imply that biotransformation is not responsible for the effects of SP600125 on AhR signaling. In conclusion, we demonstrate that SP600125 is a partial agonist of human AhR, which induces CYP1A genes.
18645229
Pharmacological inhibitors of JNK and ERK kinases SP600125 and U0126 are not appropriate tools for studies of drug metabolism because they activate aryl hydrocarbon receptor.. P Bachleda; Z DvorŠk (2008) General physiology and biophysics display abstract
Mitogen-activated protein kinases (MAPKs) are important regulators of aryl hydrocarbon receptor (AhR). An immense progress in MAPKs' biochemistry was attained with the discovery of their specific pharmacological inhibitors. Unfortunately, the inhibitors of JNK and ERK MAPKs, i.e. SP600125 and U0126, respectively, affect AhR-CYP1A signaling pathway because they are partial agonists of AhR and induce CYP1A genes. This implies that SP600125 and U0126 are inappropriate tools for studies of the role of MAPKs in AhR regulation. The results from studies using SP600125 or U126, past or future, should be interpreted with prudence regarding their stimulatory effects on AhR-CYP1A pathway.