606-25-7Relevant academic research and scientific papers
A novel small molecular STAT3 inhibitor, LY5, inhibits cell viability, cell migration, and angiogenesis in medulloblastoma cells
Xiao, Hui,Bid, Hemant Kumar,Jou, David,Wu, Xiaojuan,Yu, Wenying,Li, Chenglong,Houghton, Peter J.,Lin, Jiayuh
, p. 3418 - 3429 (2015)
Signal transducers and activators of transcription 3 (STAT3) signaling is persistently activated and could contribute to tumorigenesis of medulloblastoma. Numerous studies have demonstrated that inhibition of the persistent STAT3 signaling pathway results in decreased proliferation and increased apoptosis in human cancer cells, indicating that STAT3 is a viable molecular target for cancer therapy. In this study, we investigated a novel non-peptide, cell-permeable small molecule, named LY5, to target STAT3 in medulloblastoma cells.LY5inhibited persistentSTAT3phosphorylation and induced apoptosis in human medulloblastoma cell lines expressing constitutive STAT3 phosphorylation. The inhibition of STAT3 signaling by LY5 was confirmed by down-regulating the expression of the downstream targets of STAT3, including cyclin D1, bcl-XL, survivin, and micro-RNA-21. LY5 also inhibited the induction of STAT3 phosphorylation by interleukin-6 (IL-6), insulin-like growth factor (IGF)-1, IGF-2, and leukemia inhibitory factor in medulloblastoma cells, but did not inhibitSTAT1 and STAT5 phosphorylation stimulated by interferon-γ (IFN-γ) and EGF, respectively. In addition, LY5 blocked the STAT3 nuclear localization induced by IL-6, but did not block STAT1 and STAT5 nuclear translocation mediated by IFN-γ and EGF, respectively. A combination of LY5 with cisplatin or x-ray radiation also showed more potent effects than single treatment alone in the inhibition of cell viability in human medulloblastoma cells. Furthermore, LY5 demonstrated a potent inhibitory activity on cell migration and angiogenesis. Taken together, these findings indicate LY5 inhibits persistent and inducible STAT3 phosphorylation and suggest that LY5 is a promising therapeutic drug candidate for medulloblastoma by inhibiting persistent STAT3 signaling.
LL1, a novel and highly selective STAT3 inhibitor, displays anti-colorectal cancer activities in vitro and in vivo
Guan, Lingnan,Lai, Chong,Lai, Maode,Liu, Zhe,Wang, Huan,Yu, Wenying
, p. 298 - 313 (2020)
Background and Purpose: Signal transducer and activator of transcription 3 (STAT3) factor is associated with the development and progression of numerous types of human cancer. STAT3 activation is involved in metastasis. However, no STAT3 inhibitor has bee
Compound and medical application thereof in novel coronavirus pneumonia
-
Paragraph 0059-0062, (2021/06/09)
The invention relates to the field of medicinal chemistry and pharmacotherapeutics, in particular to a compound and medical application of the compound in novel coronavirus pneumonia, and belongs to the technical field of pharmacy. The compound is a compound shown in a formula I or a formula II, or pharmaceutically acceptable salt or ester of the compound. The invention relates to application in preparation of medicines for preventing and/or treating diseases related to novel coronavirus pneumonia.
Compound as well as preparation method and application thereof
-
Paragraph 0076-0079, (2021/06/22)
The invention relates to the field of medicinal chemistry and pharmacotherapeutics, in particular to a compound as well as a preparation method and an application thereof, and belongs to the technical field of pharmacy, the compound is a compound shown in a formula I or a formula II, or pharmaceutically acceptable salt or ester thereof, and application of the compound in preparation of medicines for preventing and/or treating diseases related to lung cancer.
Compound and medical application thereof in colorectal cancer
-
Paragraph 0074-0077; 0094; 0100-0101; 0110-0111; 0117-0118, (2021/06/13)
The invention relates to the field of medicinal chemistry and pharmacotherapeutics, in particular to a compound and medical application thereof in colorectal cancer, belongs to the technical field of pharmacy, and relates to application in tumor-related activity and the like, in particular to a compound shown in a formula I or a formula II or pharmaceutically acceptable salt or ester thereof, in particular to application in preparation of medicines for preventing and/or treating tumor-related diseases, especially colorectal cancer.
A novel small molecule LLL12B inhibits STAT3 signaling and sensitizes ovarian cancer cell to paclitaxel and cisplatin
Zhang, Ruijie,Yang, Xiaozhi,Roque, Dana M.,Li, Chenglong,Lin, Jiayuh
, (2021/05/03)
Ovarian cancer is the fifth most common cause of cancer deaths among American women. Platinum and taxane combination chemotherapy represents the first-line approach for ovarian cancer, but treatment success is often limited by chemoresistance. Therefore, it is necessary to find new drugs to sensitize ovarian cancer cells to chemotherapy. Persistent activation of Signal Transducer and Activator of Transcription 3 (STAT3) signaling plays an important role in oncogenesis. Using a novel approach called advanced multiple ligand simultaneous docking (AMLSD), we developed a novel nonpeptide small molecule, LLL12B, which targets the STAT3 pathway. In this study, LLL12B inhibited STAT3 phosphorylation (tyrosine 705) and the expression of its downstream targets, which are associated with cancer cell proliferation and survival. We showed that LLL12B also inhibits cell viability, migration, and proliferation in human ovarian cancer cells. LLL12B combined with either paclitaxel or with cisplatin demonstrated synergistic inhibitory effects relative to monotherapy in inhibiting cell viability and LLL12B-paclitaxel or LLL12B-cisplatin combination exhibited greater inhibitory effects than cisplatin-paclitaxel combination in ovarian cancer cells. Furthermore, LLL12B-paclitaxel or LLL12B-cisplatin combination showed more significant in inhibiting cell migration and growth than monotherapy in ovarian cancer cells. In summary, our results support the novel small molecule LLL12B as a potent STAT3 inhibitor in human ovarian cancer cells and suggest that LLL12B in combination with the current front-line chemotherapeutic drugs cisplatin and paclitaxel may represent a promising approach for ovarian cancer therapy.
Unlocking Amides through Selective C–N Bond Cleavage: Allyl Bromide-Mediated Divergent Synthesis of Nitrogen-Containing Functional Groups
Govindan, Karthick,Chen, Nian-Qi,Chuang, Yu-Wei,Lin, Wei-Yu
, p. 9419 - 9424 (2021/11/30)
We report a new set of reactions based on the unlocking of amides through simple treatment with allyl bromide, creating a common platform for accessing a diverse range of nitrogen-containing functional groups such as primary amides, sulfonamides, primary amines, N-acyl compounds (esters, thioesters, amides), and N-sulfonyl esters. The method has potential industrial applicability, as demonstrated through gram-scale syntheses in batch and in a continuous flow system.
Bone-seeking matrix metalloproteinase inhibitors for the treatment of skeletal malignancy
Laghezza, Antonio,Piemontese, Luca,Brunetti, Leonardo,Caradonna, Alessia,Agamennone, Mariangela,Di Pizio, Antonella,Pochetti, Giorgio,Montanari, Roberta,Capelli, Davide,Tauro, Marilena,Loiodice, Fulvio,Tortorella, Paolo
, (2020/06/18)
Matrix metalloproteinases (MMPs) are a family of enzymes involved at different stages of cancer progression and metastasis. We previously identified a novel class of bisphosphonic inhibitors, selective for MMPs crucial for bone remodeling, such as MMP-2. Due to the increasing relevance of specific MMPs at various stages of tumor malignancy, we focused on improving potency towards certain isoforms. Here, we tackled MMP-9 because of its confirmed role in tumor invasion, metastasis, angiogenesis, and immuno-response, making it an ideal target for cancer therapy. Using a computational analysis, we designed and characterized potent MMP-2/MMP-9 inhibitors. This is a promising approach to develop and clinically translate inhibitors that could be used in combination with standard care therapy for the treatment of skeletal malignancies.
METHODS AND COMPOSITIONS FOR INHIBITION OF STAT3
-
Paragraph 0237; 0238, (2019/04/26)
In one aspect, the disclosure relates to prodrug compositions of a STAT inhibitor compound. In some aspects, the STAT is STAT3. Disclosed are pharmaceutical compositions comprising the prodrug inhibitors of STAT. In various aspects, the prodrug inhibitors of STAT can be used in methods of treating an inflammatory disorder, including multiple sclerosis, or a disorder of uncontrolled cellular proliferation, such as a cancer. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.
Sulfonamide compound and synthesis method and application thereof
-
Paragraph 0122-0125, (2019/04/02)
The invention discloses a synthesis method of a sulfonamide compound represented in a formula (2). According to the method, diazonium salt is used as a reaction raw material, and under the action of an inorganic nitrogen reagent, an inorganic sulfur dioxide reagent, an additive and a phosphine reagent, the diazonium salt is reacted in a solvent at 60-100 DEG C to obtain various sulfonamide compounds. According to the method inorganic salt is used as a nitrogen atom source and a sulfur dioxide source under a metal-free catalytic condition to construct the sulfonamide compound through one step,thereby avoiding the conventional multi-step synthesis of sulfonamide by condensing unstable acid chloride and amine; and the developed sulfonamide synthesis method can be further applied to the synthesis of the arthritis drug celecoxib and the psychotropic drug sulpiride.
