CAS 129-56-6|Pyrazolanthrone (SP600125)

Introduction：Basic information about CAS 129-56-6|Pyrazolanthrone (SP600125), including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Pyrazolanthrone (SP600125) BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Safety Information
6. Customs
7. Synonyms

Common Name	Pyrazolanthrone (SP600125)
CAS Number	129-56-6	Molecular Weight	220.226
Density	1.5±0.1 g/cm3	Boiling Point	489.3±14.0 °C at 760 mmHg
Molecular Formula	C₁₄H₈N₂O	Melting Point	281~282℃
MSDS	USA	Flash Point	246.8±26.5 °C

Names

Name	Dibenzo[cd,g]indazol-6(2H)-one
Synonym	More Synonyms

Pyrazolanthrone (SP600125) BiologicalActivity

Description	SP600125 is a reversible and ATP-competitive JNK inhibitor with IC50s of 40, 40 and 90 nM for JNK1, JNK2 and JNK3, respectively.
Related Catalog	Signaling Pathways >>Autophagy >>AutophagySignaling Pathways >>MAPK/ERK Pathway >>JNKResearch Areas >>Cancer
Target	JNK1:40 nM (IC50) JNK2:40 nM (IC50) JNK3:90 nM (IC50) Autophagy
In Vitro	SP600125 is an ATP-competitive inhibitor of JNK2 with a Ki value of 0.19±0.06 μM. SP600125 inhibits the phosphorylation of c-Jun with IC50 of 5 μM to 10 μM in Jurkat T cells. In CD4+ cells, such as Th0 cells isolated from either human cord or peripheral blood, SP600125 blocks cell activation and differentiation and inhibits the expression of inflammatory genes COX-2, IL-2, IL-10, IFN-γ, and TNF-α, with IC50 of 5 μM to 12 μM[1]. In a mouse beta cells MIN6, SP600125 (20 μM) induces the phosphorylation of p38 MAPK and its downstream CREB-dependent promoter activation[2]. In HCT116 cells, SP600125 (20 μM) blocks the G2 phase to mitosis transition and induces endoreplication. This ability of SP600125 is independent of JNK inhibition, but due to its inhibition of CDK1-cyclin B activation upstream of Aurora A and Polo-like kinase 1[3].
In Vivo	Administration of SP600125 at 15 or 30 mg/kg i.v. significantly inhibits TNF-α serum levels, whereas oral administration dose-dependently blocks TNF-α expression with significant inhibition observed at 30 mg/kg per os[1]. SP600125 attenuates LPS-induced ALI in rats in vivo. The expression levels of TNF-α and IL-6 in the BALF in rats in the SP600125 group are significantly decreased[4].
Cell Assay	Determination of mRNA half-life is performed essentially, except that CD14+ cells are stimulated with (bacterial) lipopolysaccharide (LPS; 50 ng/mL) for 2 h before addition of actinomycin D (5 μg/mL). SP600125 (25 μM) or vehicle (0.5% DMSO vol/vol) is added immediately following the actinomycin D. Analysis is performed by using real-time reverse transcription (RT)-PCR. Total RNA is extracted with an RNeasy Mini kit. TNF mRNA is measured by real time RT-PCR, using a TNF Taqman probe. All data are normalized by using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression. The TNF-α forward primer is 5′-CTGGCCCAGGCAGTCAGAT-3′ and the reverse primer is 5′-TATCTCTCAGCTCCACGCCATT-3′. The Taqman probe sequence is 5′-FAM-CCTGTAGCCCATGTTGTAGCAAACCCTCA-TAMRA-3′[1].
Animal Admin	Mice[1] Female CD-1 mice (8-10 weeks of age) are dosed i.v. or per oswith SP600125 in PPCES vehicle (30% PEG-400/20% polypropylene glycol/15% Cremophor EL/5% ethanol/30% saline), final volume of 5 mL/kg, 15 min before i.v. injection with LPS in saline (0.5 mg/kg). At 90 min, a terminal bleed is obtained from the abdominal vena cava, and the serum is recovered. Samples are analyzed for mouse TNF-α by using an ELISA. Rats[4] A total of 40 male Wistar rats are randomly divided into four groups (n=10): the control group, LPS group, normal saline group (NS) and the SP600125 group. Acute lung injury (ALI) is induced via intratracheal injection of LPS. Briefly, the rats are anesthetized with pentobarbital sodium followed by intratracheal injection of 5 mg/kg LPS. The rats are then placed in a vertical position and rotated for 1 min to distribute the LPS in the lungs. Normal saline or SP600125 is administered via intraperitoneal injection (15 mg/kg) 10 min after the LPS injection.
References	[1]. Bennett BL, et al. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci U S A, 2001, 98(24), 13681-13686. [2]. Vaishnav D, et al. SP600125, an inhibitor of c-jun N-terminal kinase, activates CREB by a p38 MAPK-mediated pathway. Biochem Biophys Res Commun, 2003, 307(4), 855-860. [3]. Kim JA, et al. SP600125 suppresses Cdk1 and induces endoreplication directly from G2 phase, independent of JNK inhibition. Oncogene, 2010, 29(11), 1702-1716. [4]. Zheng Y, et al. JNK inhibitor SP600125 protects against lipopolysaccharide-induced acute lung injury via upregulation ofclaudin-4. Exp Ther Med. 2014 Jul;8(1):153-158. [5]. Zhang H, et al. SP600125 Suppresses Keap1 Expression and Results in NRF2-mediated Prevention of Diabetic Nephropathy. J Mol Endocrinol. J Mol Endocrinol. 2018 Feb;60(2):145-157.

Chemical & Physical Properties

Density	1.5±0.1 g/cm3
Boiling Point	489.3±14.0 °C at 760 mmHg
Melting Point	281~282℃
Molecular Formula	C₁₄H₈N₂O
Molecular Weight	220.226
Flash Point	246.8±26.5 °C
Exact Mass	220.063660
PSA	45.75000
LogP	3.18
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.799
InChIKey	ACPOUJIDANTYHO-UHFFFAOYSA-N
SMILES	O=C1c2ccccc2-c2n[nH]c3cccc1c23
Water Solubility	H2O: insoluble

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: CB4585000

CHEMICAL NAME :: Anthra(1,9-cd)pyrazol-6(2H)-one

CAS REGISTRY NUMBER :: 129-56-6

LAST UPDATED :: 199701

DATA ITEMS CITED :: 2

MOLECULAR FORMULA :: C14-H8-N2-O

MOLECULAR WEIGHT :: 220.24

WISWESSER LINE NOTATION :: T C6665 1A P IV OMNJ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 178 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: CSLNX* U.S. Army Armament Research & Development Command, Chemical Systems Laboratory, NIOSH Exchange Chemicals. (Aberdeen Proving Ground, MD 21010) Volume(issue)/page/year: NX#00640

Safety Information

Hazard Codes	Xi: Irritant;
Risk Phrases	R36/37/38
Safety Phrases	S26-S36
WGK Germany	3
RTECS	CB4585000
HS Code	2933990090

Customs

HS Code	2933990090
Summary	2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Synonyms

anthra[1,9-cd]pyrazol-6(2H)-one

1,9-PYRAZOLOANTHRONE

Dibenz[cd,g]indazol-6(2H)-one

1,6-dihydrodibenzo[cd,g]indazol-6-one

Dibenzo[cd,g]indazol-6(2H)-one

2H-Dibenzo[CD,G]Indazol-6-One

MFCD00022289

EINECS 204-955-6

SP600125

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