5334-43-0Relevant articles and documents
A novel synthetic compound (E)-5-((4-oxo-4h-chromen-3-yl)methyleneamino)-1-phenyl-1h-pyrazole-4-carbonitrile inhibits tnfα-induced mmp9 expression via egr-1 downregulation in mda-mb-231 human breast cancer cells
Ahn, Seunghyun,Jeong, Munki,Jung, Euitaek,Koh, Dongsoo,Lee, Young Han,Lim, Yoongho,Seo, Jeong Kon,Shin, Soon Young
, p. 1 - 15 (2020)
Breast cancer is a common malignancy among women worldwide. Gelatinases such as matrix metallopeptidase 2 (MMP2) and MMP9 play crucial roles in cancer cell migration, invasion, and metastasis. To develop a novel platform compound, we synthesized a flavonoid derivative, (E)-5-((4-oxo-4H-chromen-3-yl)methyleneamino)-1-phenyl-1H-pyrazole-4-carbonitrile (named DK4023) and characterized its inhibitory effects on the motility and MMP2 and MMP9 expression of highly metastatic MDA-MB-231 breast cancer cells. We found that DK4023 inhibited tumor necrosis factor alpha (TNFα)-induced motility and F-actin formation of MDA-MB-231 cells. DK4023 also suppressed the TNFα-induced mRNA expression of MMP9 through the downregulation of the TNFα-extracellular signal-regulated kinase (ERK)/early growth response 1 (EGR-1) signaling axis. These results suggest that DK4023 could serve as a potential platform compound for the development of novel chemopreventive/chemotherapeutic agents against invasive breast cancer.
Identification of 1-phenyl-4-cyano-5-aminopyrazoles as novel ecdysone receptor ligands by virtual screening, structural optimization, and biological evaluations
Hu, Xueping,Ma, Xiaojuan,Cui, Jialin,Liu, Haishan,Zhu, Bin,Xie, Jin,Liang, Pei,Zhang, Li
, p. 184 - 195 (2020/09/01)
Ecdysteroids initiate the molting process in insects by binding to the ecdysone receptor (EcR), which is a promising target for identifying insect growth regulators. This paper presents an in silico/in vitro screening procedure for identifying new EcR ligands. The three-step virtual screening procedure uses a three-dimensional pharmacophore model, docking and Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) rescoring routine. A novel hit (VS14) with good binding activity against Plutella xylostella EcR was identified from a library of over 200,000 chemicals. Subsequently, the 1-phenyl-4-cyano-5-aminopyrazole scaffold and twelve EcR ligands were synthesized. Their IC50 values against Plutella xylostella EcR ranged from 0.64 to 23.21?μm. Furthermore, a preliminary analysis of the structure–activity relationship for novel scaffolds provided a basis for designing new ligands with improved activity.
Pharmacophore-linked pyrazolo[3,4-d]pyrimidines as EGFR-TK inhibitors: Synthesis, anticancer evaluation, pharmacokinetics, and in silico mechanistic studies
Abulkhair, Hamada S.,Al-Karmalawy, Ahmed A.,Bayoumi, Ashraf H.,El-Adl, Khaled,El-Gamal, Kamal M.,El-Morsy, Ahmed M.,Ezz Eldin, Rogy R.,Gaber, Ahmed A.,Saleh, Marwa A.,Sherbiny, Farag F.
, (2021/09/02)
Targeting the epidermal growth factor receptors (EGFRs) with small inhibitor molecules has been validated as a potential therapeutic strategy in cancer therapy. Pyrazolo[3,4-d]pyrimidine is a versatile scaffold that has been exploited for developing potential anticancer agents. On the basis of fragment-based drug discovery, considering the essential pharmacophoric features of potent EGFR tyrosine kinase (TK) inhibitors, herein, we report the design and synthesis of new hybrid molecules of the pyrazolo[3,4-d]pyrimidine scaffold linked with diverse pharmacophoric fragments with reported anticancer potential. These fragments include hydrazone, indoline-2-one, phthalimide, thiourea, oxadiazole, pyrazole, and dihydropyrazole. The synthesized molecules were evaluated for their anticancer activity against the human breast cancer cell line, MCF-7. The obtained results revealed comparable antitumor activity with that of the reference drugs doxorubicin and toceranib. Docking studies were performed along with EGFR-TK and ADMET profiling studies. The results of the docking studies showed the ability of the designed compounds to interact with key residues of the EGFR-TK through a number of covalent and noncovalent interactions. The obtained activity of compound 25 (IC50 = 2.89 μM) suggested that it may serve as a lead for further optimization and drug development.
ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 (ENPP1) MODULATORS AND USES THEREOF
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Paragraph 00398, (2021/07/02)
Provided herein are small molecule modulators of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.