- Development of oxadiazole-based ODZ10117 as a small-molecule inhibitor of STAT3 for targeted cancer therapy
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Persistently activated STAT3 is a promising target for a new class of anticancer drug development and cancer therapy, as it is associated with tumor initiation, progression, malignancy, drug resistance, cancer stem cell properties, and recurrence. Here, we discovered 3-(2,4-dichloro-phenoxymethyl)-5-trichloromethyl-[1,2,4]oxadiazole (ODZ10117) as a small-molecule inhibitor of STAT3 to be used in STAT3-targeted cancer therapy. ODZ10117 targeted the SH2 domain of STAT3 regardless of other STAT family proteins and upstream regulators of STAT3, leading to inhibition of the tyrosine phosphorylation, dimerization, nuclear translocation, and transcriptional activity of STAT3. The inhibitory effect of ODZ10117 on STAT3 was stronger than the known STAT3 inhibitors such as S3I-201, STA-21, and nifuroxazide. ODZ10117 suppressed the migration and invasion, induced apoptosis, reduced tumor growth and lung metastasis, and extended the survival rate in both in vitro and in vivo models of breast cancer. Overall, we demonstrated that ODZ10117 is a novel STAT3 inhibitor and may be a promising agent for the development of anticancer drugs.
- Kim, Byung-Hak,Lee, Haeri,Song, Yeonghun,Park, Joon-Suk,Gadhe, Changdev G.,Choi, Jiwon,Lee, Chung-Gi,Pae, Ae Nim,Kim, Sanghee,Ye, Sang-Kyu
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- COMPOUND HAVING STAT3 INHIBITORY ACTIVITY AND USE THEREOF
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The present invention relates to a compound exhibiting STAT3 inhibitory activity, or a pharmaceutically acceptable salt, solvate or hydrate of the same, and pharmaceutical uses of these. The compounds of the present invention efficiently inhibit the abnormal activity of STAT3 associated with various diseases and thus can be usefully utilized for the prevention and treatment of various STAT3-related diseases associated with cancer, autoimmune diseases, inflammatory diseases and the like.
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Paragraph 0058-0059
(2020/12/03)
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- Skin whitening composition and use thereof
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The present invention relates to a composition for skin whitening and a use thereof, does not cause cytotoxicity, and can provide a skin whitening effect by suppressing the expression and activity of an enzyme and a transcription factor which induce the production of melanin.
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Paragraph 0098-0102
(2021/01/14)
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- Compounds selectively targeting STAT3 and Uses thereof
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The present invention relates to a compound having an STAT3 inhibitory activity, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, and a pharmaceutical use thereof. The compound of the present invention efficiently inhibits abnormal activities of STAT3 in association with various diseases, and thus can be useful in preventing and treating various STAT3-related diseases, such as cancers, autoimmune disorders, and inflammatory diseases.
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Paragraph 0084 - 0088
(2017/05/02)
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- Synthesis and Antitubercular Activity of 4-(5-Nitro-2-furyl/2-pyrazinyl/1-adamantyl)-2-(alkyl/aryl/arylamino)thiazoles
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The reaction of haloketones, obtained from Arndt-Eistert reaction on the acid chlorides of 1-adamantane, 5-nitrofuroic acid and pyrazine-2-carboxylic acid, with different thioamides and thioureas affords the title thiazoles (I-III).Some of them exhibit interesting antitubercular activity at 6.25 to 0.38 μg/ml concentration against H37Rv strain of M. tubercolosis in vitro testing.The structure activity relationship (SAR) has also been discussed.
- Khadse, B. G.,Lokhande, S. R.,Bhamaria, R. P.,Prabhu, S. R.
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p. 856 - 860
(2007/10/02)
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- THE SALT-FREE SYNTHESIS OF ARYL ETHERS USING METHYL TRICHLOROACETATE
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Metyl trichloroacetate is an effective reagent for salt-free synthesis of aryl ethers and anisoles from phenols.
- Renga, James M.,Wang, Pen-Chung
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- Composition and process for promoting the growth of crop plants
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Compounds of the formula wherein Ar is (substituted) phenyl or naphthyl, X is oxygen, sulfur, SO or SO2, n is 1-3 and R is CN or C(NH2)NOR1, (wherein R1 is preferably hydrogen) are useful as safeners in crop protection.
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