CGP-57380

• CAT Number: I003908
• CAS Number: 522629-08-9
• Molecular Formula: C₁₁H₉FN₆
• Molecular Weight: 244.23
• Purity: ≥95%
• Target: Mnk1
• Solubility: DMSO: ≥ 43 mg/mL
• Storage: -20°C
• IC50: 2.2 uM
• InChI: InChI=1S/C11H9FN6/c12-6-1-3-7(4-2-6)16-11-8-9(13)14-5-15-10(8)17-18-11/h1-5H,(H4,13,14,15,16,17,18)
• InChIKey: UQPMANVRZYYQMD-UHFFFAOYSA-N
• SMILES: C1=CC(=CC=C1NC2=C3C(=NC=NC3=NN2)N)F

CGP-57380 (CAT: I003908) is a potent and selective inhibitor of p38 MAPK (mitogen-activated protein kinase). It functions by binding to the ATP-binding site of p38 MAPK, thereby inhibiting its activity. p38 MAPK is a key signaling molecule involved in various cellular processes, including inflammation, stress response, and cell proliferation. By inhibiting p38 MAPK, CGP-57380 can suppress the activation of downstream signaling pathways and modulate the cellular response to stress and inflammation. This compound has been widely used in preclinical and experimental studies to investigate the role of p38 MAPK in various diseases, such as inflammatory disorders, neurodegenerative diseases, and cancer.

Reference

1. Theranostics. 2017 May 30;7(7):2134-2149. doi: 10.7150/thno.17665. eCollection
2017.
Suppression Of β-catenin Nuclear Translocation By CGP57380 Decelerates Poor
Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal
Carcinoma.
Wang W(1), Wen Q(1), Luo J(1), Chu S(1), Chen L(1), Xu L(1), Zang H(1), Alnemah
MM(1), Li J(2), Zhou J(2), Fan S(1).
Author information:
(1)Department of Pathology, Second Xiangya Hospital, Central South University,
Changsha, Hunan, 410011, China.
(2)Department of Pathology, Xiangya Hospital, Central South University, Changsha,
Hunan, 410008, China.
Nuclear localization of β-catenin is essential for the progression of various
human cancers via transcriptional upregulation of downstream genes. The MAP
kinase interacting serine/threonine kinase (MNK)-eukaryotic translation
initiation factor 4E (eIF4E) axis has been reported to activate Wnt/β-catenin
signaling, and CGP57380, an inhibitor of MNK kinases, inhibits the proliferation
of multiple cancers. In this study, we showed that β-catenin signaling (including
β-catenin, cyclin D1, c-Myc, and MMP-7) and p-eIF4E expression were elevated in
nasopharyngeal carcinoma (NPC) compared with non-cancerous nasopharyngeal
epithelial tissues, and was associated with clinical characteristics of NPC
patients. Lymph node metastasis, gender, aberrant β-catenin expression, and
elevated levels of MMP-7 and cyclin D1 were independent prognostic factors.
Significantly, expression of p-eIF4E was positively correlated with β-catenin,
and targeting the MNK-eIF4E axis with CGP57380 downregulated β-catenin in the
nucleus, which in turn decreased proliferation, cell cycle progression,
migration, invasion, and metastasis of NPC in vitro and in vivo. CGP57380 also
potentiated radiation-induced apoptosis in NPC. Moreover, CGP57380 upregulated
β-catenin in the cytoplasm thus blocking epithelial-mesenchymal transition (EMT),
a key mechanism in cancer cell invasiveness and metastasis. Mechanistically,
inhibition of β-catenin nuclear translocation by CGP57380 was dependent on AKT
activation. Notably, identification of the MNK/eIF4E/β-catenin axis might provide
a potential target for overcoming the poor prognosis mediated by β-catenin in
NPC.
2. Oncotarget. 2016 May 10;7(19):27787-801. doi: 10.18632/oncotarget.8497.
CGP57380 enhances efficacy of RAD001 in non-small cell lung cancer through
abrogating mTOR inhibition-induced phosphorylation of eIF4E and activating
mitochondrial apoptotic pathway.
Wen Q(1), Wang W(1), Luo J(1), Chu S(1), Chen L(1), Xu L(1), Zang H(1), Alnemah
MM(1), Ma J(2), Fan S(1).
Author information:
(1)Department of Pathology, the Second Xiangya Hospital, Central South
University, Changsha, Hunan, 410011, China.
(2)Cancer Research Institute of Central South University, Changsha, Hunan,
410078, China.
The mammalian target of rapamycin (mTOR) is a potentially important therapeutic
target in a broad range of cancer types. mTOR inhibitors such as rapamycin and
its analogs (rapalogs) have been proven effective as anticancer agents in
non-small cell lung cancer (NSCLC), whereas they strongly enhance phosphorylation
of eukaryotic translation initiation factor 4E (eIF4E) and activation of Akt,
which cause resistance to mTOR-targeted therapy after an initial response.
Rapamycin induces eIF4E phosphorylation by activating MAPK-interacting kinases
(Mnks), and therefore targeting Mnk/eIF4E pathway represents a potential
therapeutic strategy for the treatment of NSCLC. Here, our results showed that
over-expression of p-Mnk1 and p-eIF4E was significantly associated with poor
overall survival of NSCLC patients and high expression of p-Mnk1 might act as an
independent prognostic biomarker for these patients. Meanwhile, inhibiting Mnk1
expression by Mnk inhibitor (CGP57380) could abrogate rapalogs (RAD001)-induced
eIF4E phosphorylation and Akt activation. Furthermore, combination of CGP57380
and RAD001 could induce NSCLC cells apoptosis via activating intrinsic
mitochondrial pathway, and exert synergistic antitumor efficacy both in vitro and
in vivo. In conclusion, combination of targeting both mTOR and Mnk/eIF4E
signaling pathways to enhance effectiveness of mTOR-targeted cancer therapy might
be significant innovation for the personalized treatment of NSCLC.