129-56-6 Usage
Description
1,9-Pyrazoloanthrone, also known as SP-600125, is a member of the anthrapyrazoles class and is an anthra[1,9-cd]pyrazole substituted at position 6 by an oxo group. It is a potent, cell-permeable, selective, and reversible inhibitor of c-Jun N-terminal kinase (JNK) with an IC50 range from 40 to 90 nM. The inhibition is competitive with respect to ATP and exhibits over 300-fold greater selectivity for JNK as compared to ERK1 and p38-2 MAP kinases. It has anti-inflammatory activity and is known to inhibit the expression of presenilin-1 and Notch signaling in mouse brain.
Uses
Used in Cellular Research:
1,9-Pyrazoloanthrone is used as a broad-spectrum serine/threonine kinase inhibitor of JNK for testing the stimulation of myogenesis in C2C12 myoblasts and the effects on oxysterol-induced necrosis in HepG2 cells.
Used in Pharmaceutical Applications:
1,9-Pyrazoloanthrone is used as a Jun N-terminal kinase (JNK) inhibitor for its anti-inflammatory activity and its ability to inhibit the expression of presenilin-1 and Notch signaling in mouse brain.
Used in Enzyme Inhibition Studies:
1,9-Pyrazoloanthrone is used as a potent inhibitor of c-Jun N-terminal kinase (JNK) to block the phosphorylation of c-Jun and the expression of IL-2, IFN-γ, TNF-α, and COX-2 in cells. It also blocks IL-1-induced accumulation of phospho-Jun and the induction of c-Jun transcription.
Used in Drug Development:
1,9-Pyrazoloanthrone is used as a lead compound in the development of novel drug delivery systems to enhance its applications and efficacy against various diseases, particularly in the context of cancer research and treatment.
Biological Activity
Selective inhibitor of c-Jun N-terminal kinase (JNK). Competitively and reversibly inhibits JNK1, 2 and 3 (IC 50 = 40-90 nM) with negligible activity at ERK2, p38 β and a range of enzymes (IC 50 > 10 μ M). Active in vivo . Shown to have reduced selectivity over other protein kinases under certain conditions. Protects renal tubular epithelial cells against ischemia/reperfusion-induced apoptosis. Also available as part of the MAPK Inhibitor Tocriset? .
Biochem/physiol Actions
SP600125 is an anthrapyrazolone inhibitor of JNK that competes with ATP to inhibit the phosphorylation of c-Jun. It prevents the activation of inflammatory genes such as COX-2, IL-2 IFN-γ and TNF-α.8,9 It prevents the activation of JNK after brain ischemia and may be effective in treatment of ischemic stroke.10
Safety Profile
Poison by intravenous route.When heated to decomposition it emits toxic fumes ofNOx.
References
1)Bennett et al. (2001), SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase; Proc. Natl. Acad. Sci. USA., 98 13681
2) Rahman et al. (2012), Intraperitoneal injection of JNK-specific inhibitor SP600125 inhibits the expression of presenilin-1 and Notch signaling in mouse brain without induction of apoptosis; Brain Res., 1448 117
Check Digit Verification of cas no
The CAS Registry Mumber 129-56-6 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,2 and 9 respectively; the second part has 2 digits, 5 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 129-56:
(5*1)+(4*2)+(3*9)+(2*5)+(1*6)=56
56 % 10 = 6
So 129-56-6 is a valid CAS Registry Number.
InChI:InChI=1/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)
129-56-6Relevant articles and documents
Structural and biological evaluation of halogen derivatives of 1,9-pyrazoloanthrones towards the design of a specific potent inhibitor of c-Jun-N-terminal kinase (JNK)
Ganduri, Ramesh,Singh, Vikas,Biswas, Ansuman,Karothu, Durga Prasad,Sekar, Kanagaraj,Balaji, Kithiganahalli N.,Guru Row, Tayur N.
, p. 10651 - 10660 (2018)
c-Jun N-terminal kinase (JNK), a member of the MAPK family, is associated with a variety of diseases and immune responses. To dissect the mechanistic role of JNKs in such processes, a specific inhibitor for JNKs holds great value. SP600125 is a widely used inhibitor of JNKs despite its non-specific activity. In an effort to obtain better specific inhibitors, three anthrapyrazolone halogenated derivatives have been synthesized and characterized. Among the three derivatives, 5-chloro-2-(2-chloroethyl)dibenzo[cd,g] indazol-6(2H)-one is clearly established as a specific inhibitor of JNK with augmented expression of chemokines in LPS-activated macrophages based on modelling studies followed by in vitro and ex vivo evaluation.
Method for producing pyrazolanthone by using 1 - aminoanthraquinone (by machine translation)
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Paragraph 0019-0048, (2020/11/10)
The invention discloses a method for producing pyrazolanthone by using 1 - aminoanthraquinone, and belongs to the technical field of chemical engineering. The method comprises the following steps: (1) adding sulfuric acid in the reaction kettle, adding 65 - 70 °C aminoanthraquinone to the reaction kettle, warming up to 2 - 3h, heating the material into a reduction kettle; (1 -) adding sulfuric acid to the reaction kettle; and (2) carrying out cyclization reaction in a time-sharing stage reaction mode to obtain the pyrazolanthrapyone after the reaction is finished to 5 - 10 °C 3, adding the sodium nitrite solution to the reaction kettle after the reaction is finished 4 - 5h. The preparation method is higher in product yield and higher in purity, and can be well applied to dye production. (by machine translation)
Methods for treating inflammatory conditions or inhibiting JNK
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Page 14, (2010/02/06)
This invention generally relates to methods for treating or preventing an inflammatory disease or disorder comprising administering to a patient in need thereof an effective amount of a Pyrazoloanthrone Derivative having the following structure: or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are as defined herein.
