General
Preferred name
pyrazolanthrone
Synonyms
SP600125 ()
SP 600125 ()
Nsc75890 ()
1PMV ()
JNK Inhibitor II ()
2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One ()
P&D ID
PD002737
CAS
129-56-6
120093-15-4
Tags
available
drug candidate
Drug indication
Discovery agent
Drug Status
experimental
Structure
PD002737
pyrazolanthrone
RO5
MW
220.06
HBA
2
HBD
1
RB
0
LOGP
2.77
7
21
0
9
Structure formats
SMILES
O=C1c2ccccc2-c2n[nH]c3cccc1c23
InChI
InChI=1S/C14H8N2O/c17-14-9-5-2-1-4-8(9)13-12-10(14)6-3-7-11(12)15-16-13/h1-7H,(H,15,16)
InChIkey
ACPOUJIDANTYHO-UHFFFAOYSA-N
MOL
pyrazolanthrone RDKit 2D 17 20 0 0 0 0 0 0 0 0999 V2000 3.0000 -2.5981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 -2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9672 -2.9099 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.1240 -4.4017 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.7537 -5.0118 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0134 -6.3242 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4784 -6.4810 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3601 -5.2674 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -3.8971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -3.8971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 16 2 1 0 8 3 1 0 17 9 1 0 17 12 2 0 M END > <ID> PD002737 > <Name> pyrazolanthrone
Description
(extracted from source data)
DESCRIPTION SP600125 is an ATP-competitive, pan JNK inhibitor with potent activity against JNK1, JNK2 and JNK3 . Off targets including the aryl hydrocarbon receptor (AhR; agonist) , Mps1 (TTK, a tyrosine, serine and threonine kinase) , and some serine/threonine kinases (Aurora kinase A, FLT3, MELK, and TRKA) have been identified. (GtoPdb)
DESCRIPTION Selective JNK inhibitor.
DESCRIPTION inhibitor of Jun N-terminal kinase (JNK) 1/2/3 (Informer Set)
DESCRIPTION Selective c-Jun N-terminal kinase (c-JNK) inhibitor. (LOPAC library)
DESCRIPTION PDE3 inhibitor (Tocris Bioactive Compound Library)
DESCRIPTION Novel and selective JNK inhibitor (Tocriscreen Total)
DESCRIPTION SP-600125 is a specific JNK inhibitor. SP600125 kills p53-deficient cells more efficiently than their p53-proficient counterparts, in vitro. Similar observations were obtained in vivo, in mice carrying p53-deficient and -proficient human xenografts. (BOC Sciences Bioactive Compounds)
Protein targets
9
7.4
7.08
MAPK9 Mitogen-activated protein kinase 9 inhibitor BIOCHEM 1x
5
6
7.4
7
MAPK8 Mitogen-activated protein kinase 8 inhibitor
12
6
7.4
MAPK8,MAPK9 JNK1/JNK2
0
1
7.05
7.66
MAPK10 Mitogen-activated protein kinase 10 inhibitor CELL-BASED 3.8x
4
11
7.01
TTK Dual specificity protein kinase TTK
0
1
6.14
ERN1 Serine/threonine-protein kinase/endoribonuclease IRE1
1
1
5.9
PDPK1 3-phosphoinositide-dependent protein kinase 1
20
1
5.62
HDAC6 Histone deacetylase 6
11
1
5.38
MAPK10,MAPK8... c-Jun N-terminal kinase, JNK
0
1
Target pathways
44
Activation of AKT2
R-HSA-165158
PDPK1
Activation of BIM and translocation to mitochondria
R-HSA-111446
MAPK8
Activation of BMF and translocation to mitochondria
R-HSA-139910
MAPK8
Activation of the AP-1 family of transcription factors
R-HSA-450341
MAPK10
MAPK9
MAPK8
Aggrephagy
R-HSA-9646399
HDAC6
CD28 dependent PI3K/Akt signaling
R-HSA-389357
PDPK1
Chaperone Mediated Autophagy
R-HSA-9613829
HDAC6
Cilium Assembly
R-HSA-5617833
HDAC6
CLEC7A (Dectin-1) signaling
R-HSA-5607764
PDPK1
Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-5674400
PDPK1
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2894862
HDAC6
Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2644606
HDAC6
Downstream TCR signaling
R-HSA-202424
PDPK1
Estrogen-stimulated signaling through PRKCZ
R-HSA-9634635
PDPK1
FCERI mediated MAPK activation
R-HSA-2871796
MAPK10
MAPK9
MAPK8
FCERI mediated NF-kB activation
R-HSA-2871837
PDPK1
G beta:gamma signalling through PI3Kgamma
R-HSA-392451
PDPK1
GPVI-mediated activation cascade
R-HSA-114604
PDPK1
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-9856530
PDPK1
HSF1 activation
R-HSA-3371511
HDAC6
Integrin signaling
R-HSA-354192
PDPK1
Interleukin-38 signaling
R-HSA-9007892
MAPK8
IRE1alpha activates chaperones
R-HSA-381070
ERN1
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-450321
MAPK10
MAPK9
MAPK8
Late endosomal microautophagy
R-HSA-9615710
HDAC6
Notch-HLH transcription pathway
R-HSA-350054
HDAC6
NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2122947
HDAC6
NRAGE signals death through JNK
R-HSA-193648
MAPK8
NRIF signals cell death from the nucleus
R-HSA-205043
MAPK8
Oxidative Stress Induced Senescence
R-HSA-2559580
MAPK10
MAPK9
MAPK8
PIP3 activates AKT signaling
R-HSA-1257604
PDPK1
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693565
MAPK8
Regulation of TP53 Degradation
R-HSA-6804757
PDPK1
RHO GTPases activate PKNs
R-HSA-5625740
PDPK1
Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-2730905
PDPK1
RSK activation
R-HSA-444257
PDPK1
RUNX2 regulates osteoblast differentiation
R-HSA-8940973
HDAC6
SARS-CoV-1 targets host intracellular signalling and regulatory pathways
R-HSA-9735871
PDPK1
SARS-CoV-2 targets host intracellular signalling and regulatory pathways
R-HSA-9755779
PDPK1
Signaling by ALK fusions and activated point mutants
R-HSA-9725370
MAPK9
MAPK8
Transcriptional regulation by RUNX2
R-HSA-8878166
HDAC6
VEGFR2 mediated cell proliferation
R-HSA-5218921
PDPK1
VEGFR2 mediated vascular permeability
R-HSA-5218920
PDPK1
WNT5:FZD7-mediated leishmania damping
R-HSA-9673324
MAPK8
References
17
2023 Synthesis-accessibility-oriented design of c-Jun N-terminal kinase 1 inhibitor.
Qian H, Ding Y et al. Eur J Med Chem
2023 The structure-based optimization of 3-substituted indolin-2-one derivatives as potent and isoform-selective c-Jun N-terminal kinase 3 (JNK3) inhibitors and biological evaluation.
Li Z, Zhu G et al. Eur J Med Chem
2022 Unraveling the Design and Discovery of c-Jun N-Terminal Kinase Inhibitors and Their Therapeutic Potential in Human Diseases.
Zhu Y, Shuai W et al. J Med Chem
2022 Design, synthesis, and biological evaluation of a new series of pyrazole derivatives: Discovery of potent and selective JNK3 kinase inhibitors.
Abu Rabah RR, Sebastian A et al. Bioorg Med Chem
2022 Kinase Inhibitors as Underexplored Antiviral Agents.
García-Cárceles J, Caballero E et al. J Med Chem
HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators (dataset)
2020 Rational modification, synthesis and biological evaluation of 3,4-dihydroquinoxalin-2(1H)-one derivatives as potent and selective c-Jun N-terminal kinase 3 (JNK3) inhibitors.
Dou X,Huang H et al. Eur J Med Chem
2019 Synthesis, biological evaluation, and molecular modeling of 11H-indeno[1,2-b]quinoxalin-11-one derivatives and tryptanthrin-6-oxime as c-Jun N-terminal kinase inhibitors.
Schepetkin IA, Khlebnikov AI et al. Eur J Med Chem
2019 Molecular design and anticancer activities of small-molecule monopolar spindle 1 inhibitors: A Medicinal chemistry perspective.
Wang S, Zhang M et al. Eur J Med Chem
2016 Discovery and antiparasitic activity of AZ960 as a Trypanosoma brucei ERK8 inhibitor.
Valenciano AL, Ramsey AC et al. Bioorg Med Chem
2016 Structural and Functional Analysis of the Allosteric Inhibition of IRE1α with ATP-Competitive Ligands.
Feldman HC; Tong M et al.
2016 Bidirectional Allosteric Communication between the ATP-Binding Site and the Regulatory PIF Pocket in PDK1 Protein Kinase.
Schulze JO; Saladino G et al.
2013 A small molecule bidentate-binding dual inhibitor probe of the LRRK2 and JNK kinases.
Feng Y; Chambers JW et al.
2012 Discovery of potent and selective covalent inhibitors of JNK.
Zhang T; Inesta-Vaquera F et al.
2003 The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity.
Scapin G; Patel SB et al.
2001 SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase.
Bennett BL, Sasaki DT et al. Proc. Natl. Acad. Sci. U.S.A.
AID 504657
Cell lines
56
5.58
KM12
5.45
CAKI-1
5.23
TK-10
5.18
ACHN
5.15
A498
5.09
HCT-15
5.02
HCC 2998
5.01
NCI-H460
4.98
UO-31
4.96
SW-620
4.95
IGROV-1
4.91
NCI-H522
4.89
MDA-MB-435
4.88
SR
4.84
UACC-62
4.83
A549
4.83
SK-MEL-5
4.83
SN12C
4.82
OVCAR-3
4.79
CCRF-CEM
4.79
Malme-3M
4.77
SNB-75
4.73
RPMI-8226
4.73
SF-268
4.71
COLO 205
4.7
EKVX
4.69
MOLT-4
4.68
SK-OV-3
4.68
RXF 393
4.66
OVCAR-8
4.65
SF-295
4.65
NCI/ADR-RES
4.64
NCI-H226
4.64
U-251
4.63
PC-3
4.62
NCI-H23
4.61
OVCAR-5
4.6
NCI-H322M
4.59
HT-29
4.57
786-0
4.55
DU-145
4.54
SK-MEL-2
4.53
UACC-257
4.51
BT-549
4.5
OVCAR-4
4.49
SF-539
4.43
SK-MEL-28
4.42
HOP-92
4.38
HL-60(TB)
4.35
HCT-116
4.31
K562
4.31
MCF7
4.3
SNB-19
4.26
Hs-578T
4.18
MDA-MB-231
4.16
HOP-62
Organisms
1
6.24
Trypanosoma brucei
Compound Sets
21
AdooQ Bioactive Compound Library
A10860
Axon Medchem Screening Library
2519
BOC Sciences Bioactive Compounds
sp-600125-cas-129-56-6-item-84-56857
Cayman Chemical Bioactives
10010466
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DB01782
DrugMAP
DMDN12L
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
EOS101472
Guide to Pharmacology
5273
Informer Set
44511
Ki Database
SP600125
LINCS compound set
10162-101
LOPAC library
MedChem Express Bioactive Compound Library
HY-12041
Novartis Chemogenetic Library (NIBR MoA Box)
Selleckchem Bioactive Compound Library
SP600125
TargetMol Bioactive Compound Library
T3109
Tocris Bioactive Compound Library
1496
Tocriscreen Total
Available from
13
AdooQ Bioactive Compound Library
A10860
Axon Medchem Screening Library
2519
BOC Sciences Bioactive Compounds
sp-600125-cas-129-56-6-item-84-56857
Cayman Chemical Bioactives
10010466
Enamine BioReference Compounds
LOPAC library
Mcule
MCULE-7820194475
MedChem Express Bioactive Compound Library
HY-12041
MolPort
MolPort-000-628-456
MolPort-009-019-397
MolPort-002-914-349
Molport-002-914-349
Molport-009-019-397
Molport-000-628-456
Selleckchem Bioactive Compound Library
SP600125
TargetMol Bioactive Compound Library
T3109
Tocris Bioactive Compound Library
1496
Tocriscreen Total
External IDs
40
ChEMBL CHEMBL7064
GtoPdb 5273
PubChem 8515 168320041
ZINC ZINC000096298875
BindingDB 16018 50433916
Brenda 220854 14439 5385 155385 123218 155507
CCDC JORMUA
ChEBI 90695
ChemicalBook CB6354608
ChemSpider 8201
COCONUT CNP0569312.0
CompTox DTXSID2040525
DrugBank DB01782
eMolecules 594393 5778544
FDA SRS 1TW30Y2766
GSRS d28b6911-371d-4...
HMDB HMDB0244499
IBM NIH E45364873BCCD34... 42D14587F682EB7...
LINCS LSM-1163
Mcule MCULE-7820194475
MolPort MolPort-000-628-456 MolPort-009-019-397 MolPort-002-914-349 Molport-002-914-349 Molport-009-019-397 Molport-000-628-456
Nikkaji J55.382D
PDB 537
PubChem TPS 15172126
Selleck SP600125
SureChEMBL SCHEMBL170980
Properties
(calculated by RDKit )
Molecular Weight
220.06
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
1
Rotatable Bonds
0
Ring Count
4
Aromatic Ring Count
3
cLogP
2.77
TPSA
45.75
Fraction CSP3
0.0
Chiral centers
0.0
Largest ring
6.0
QED
0.49
Structural alerts
0
No structural alerts detected
Custom attributes
(extracted from source data)
Target
MAPK10
MAPK8
MAPK9
Aurora A
JNK1
JNK2
JNK3
TrkA
MAPK10, MAPK8, MAPK8IP1, MAPK9, TTK
Ferroptosis
Apoptosis related,Aurora Kinase,Autophagy,FLT3,JNK,Serine/threonin kinase,Trk receptor
Compound status
probe
Selectivity
c-JNK
Pathway
Cell Cycle/Checkpoint
MAPK
Tyrosine Kinase/Adaptors
Chromatin/Epigenetic
Apoptosis
Autophagy
MAPK/ERK Pathway
Primary Target
JNK/c-Jun
MOA
Aurora Kinase
JNK
Trk receptor
Inhibitor
AP-1 Inhibitors
Inhibitors of Signal Transduction Pathways
Leucine-Rich Repeat Kinase 2 (LRRK2
Dardarin) Inhibitors
SAPK1a (JNK2) Inhibitors
SAPK1b (JNK3) Inhibitors
SAPK1c (JNK1) Inhibitors
"AP-1 Inhibitors
SAPK1c (JNK1) Inhibitors"
JNK inhibitor
Member status
member
Source data