- A novel small molecular STAT3 inhibitor, LY5, inhibits cell viability, cell migration, and angiogenesis in medulloblastoma cells
-
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.
- Xiao, Hui,Bid, Hemant Kumar,Jou, David,Wu, Xiaojuan,Yu, Wenying,Li, Chenglong,Houghton, Peter J.,Lin, Jiayuh
-
-
Read Online
- LL1, a novel and highly selective STAT3 inhibitor, displays anti-colorectal cancer activities in vitro and in vivo
-
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
- Guan, Lingnan,Lai, Chong,Lai, Maode,Liu, Zhe,Wang, Huan,Yu, Wenying
-
-
Read Online
- Compound and medical application thereof in novel coronavirus pneumonia
-
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.
- -
-
Paragraph 0059-0062
(2021/06/09)
-
- Compound as well as preparation method and application thereof
-
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.
- -
-
Paragraph 0076-0079
(2021/06/22)
-
- Compound and medical application thereof in colorectal cancer
-
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.
- -
-
Paragraph 0074-0077; 0094; 0100-0101; 0110-0111; 0117-0118
(2021/06/13)
-
- A novel small molecule LLL12B inhibits STAT3 signaling and sensitizes ovarian cancer cell to paclitaxel and cisplatin
-
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.
- Zhang, Ruijie,Yang, Xiaozhi,Roque, Dana M.,Li, Chenglong,Lin, Jiayuh
-
-
- Unlocking Amides through Selective C–N Bond Cleavage: Allyl Bromide-Mediated Divergent Synthesis of Nitrogen-Containing Functional Groups
-
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.
- Govindan, Karthick,Chen, Nian-Qi,Chuang, Yu-Wei,Lin, Wei-Yu
-
p. 9419 - 9424
(2021/11/30)
-
- Bone-seeking matrix metalloproteinase inhibitors for the treatment of skeletal malignancy
-
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.
- 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
-
-
- METHODS AND COMPOSITIONS FOR INHIBITION OF STAT3
-
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.
- -
-
Paragraph 0237; 0238
(2019/04/26)
-
- Sulfonamide compound and synthesis method and application thereof
-
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.
- -
-
Paragraph 0122-0125
(2019/04/02)
-
- Metal-free construction of primary sulfonamides through three diverse salts
-
In this report, the first metal-free construction of primary sulfonamides through a direct three-component reaction of sodium metabisulfite, sodium azide and aryldiazonium has been established. Readily available inorganic Na2S2O5 and NaN3 were applied as the sulfur dioxide surrogate and nitrogen source respectively. The widely used sulfonamide drugs Celecoxib and Sulpiride, which possess multiple heteroatoms and active hydrogen containing functional groups, are efficiently installed with -SO2NH2 groups at a late stage. Control experiments and kinetic studies demonstrated that aryl radicals, sulfonyl radicals and conjugated phosphine imine radicals are involved in this transformation.
- Wang, Ming,Fan, Qiaoling,Jiang, Xuefeng
-
supporting information
p. 5469 - 5473
(2019/01/03)
-
- Compound LL-1 preparation method
-
The invention relates to the field of medicinal chemistry and pharmacotherapeutics, particularly to a new compound LL-1 preparation method, which has characteristics of simpleness, low cost, and high yield. According to the present invention, with the pre
- -
-
Paragraph 0033-0036
(2017/08/31)
-
- Cu-catalyzed aerobic oxidative three-component coupling route to N -sulfonyl amidines via an ynamine intermediate
-
Cu-catalyzed aerobic oxidative three-component coupling of a terminal alkyne, secondary amine, and sulfonamide enables efficient synthesis of amidines. The use of Cu(OTf)2 (5 mol %) produces amidines selectively without Glaser-Hay alkyne homocoupling products. Preliminary studies suggest that the reaction pathway involves initial oxidative coupling of the terminal alkyne with the secondary amine, followed by hydroamidation of the ynamine intermediate with the sulfonamide.
- Kim, Jinho,Stahl, Shannon S.
-
p. 2448 - 2454
(2015/04/14)
-
- Regioselective one-pot C-N coupling of substituted naphthoquinones: Selective intramolecular ring fusion of sulfonamides
-
The first one-pot copper-catalyzed highly regioselective C-N bond formation between aryl/alkyl amines and sulfonamide-substituted naphthoquinones was accomplished. Facile chemoselective routes obtained diverse ring-opening 6-amino/anilino-naphthalen-dione-1-sulfonamides and ring-fused 6-amino/aniline-5H-naphth[1,8-cd]isothiazol-5-one,1,1-dioxides with great functional group tolerance. Regiochemistry was confirmed by 1D- and 2D-NMRs.
- Yu, Wenying,Li, Chenglong
-
p. 459 - 464
(2014/01/06)
-
- STAT3 INHIBITORS AND THEIR ANTICANCER USE
-
In one aspect, the invention relates to substituted substituted 6-amino-5,8-dioxo-5,8- dihydronaphthalene- 1 -sulfonamide analogs and derivatives thereof, substituted 4-amino-5H- naphtho[l,8-cd]isothiazol-5-one 1,1-dioxide analogs and derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. 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 invention.
- -
-
Paragraph 00458; 00459
(2014/03/22)
-
- Catalytic asymmetric synthesis of dihydroquinazolinones from imines and 2-aminobenzamides
-
An unprecedented catalytic asymmetric synthesis of aminal-containing heterocyclic compounds has been developed from imines and tethered nitrogen/nitrogen nucleophiles. In the presence of 10mol% of a commercially available chiral phosphoric acid, a range of aromatic, α,β- unsaturated, and aliphatic imines react with 2-aminobenzamides to give dihydroquinazolinones in good to excellent yields and ee. The enantioselectivity is significantly affected by the imine N-substituent through non-bonding interactions with the chiral phosphoric acid and the 2-aminobenzamide. Copyright
- Cheng, Dao-Juan,Tian, Yu,Tian, Shi-Kai
-
supporting information; experimental part
p. 995 - 999
(2012/06/01)
-
- TRANSCRIPTION FACTOR INHIBITORS AND RELATED COMPOSITIONS, FORMULATIONS AND METHODS
-
The present invention provides small molecules useful to affect cancer cells, along with related methods. The present compounds, formulations, kits and methods are useful for a variety of research, diagnostic and therapeutic purposes. STAT3 inhibitors, particularly LLL12, are disclosed. The STAT3 inhibitors are useful to treat breast cancer in general and breast cancer initiating cells in particular.
- -
-
Page/Page column 14
(2011/06/23)
-
- Novel N-dealkylation of N-alkyl sulfonamides and N,N-dialkyl sulfonamides with periodic acid catalyzed by chromium(III) acetate hydroxide
-
Chromium(III) acetate hydroxide has been found to be an efficient catalyst for N-dealkylation of N-alkyl sulfonamides and N,N-dialkyl sulfonamides to furnish sulfonamides in good to excellent yields with periodic acid in acetonitrile at room temperature.
- Xu, Liang,Zhang, Suhong,Trudell, Mark L.
-
p. 1901 - 1904
(2007/10/03)
-
- Oxidation of aromatic and aliphatic triisopropylsilanylsulfanyls to sulfonyl chlorides: Preparation of sulfonamides
-
A series of aromatic and aliphatic triisopropylsilanylsulfanyls were prepared and oxidized to the sulfonyl chlorides with KNO3/SO 2Cl2. The sulfonyl chlorides were characterized via their conversion to sulfonamides.
- Gareau, Yves,Pellicelli, Jonathan,Laliberté, Sébastien,Gauvreau, Danny
-
p. 7821 - 7824
(2007/10/03)
-
- Topical compositions comprising protected functional thiols
-
This invention relates to a topical composition for treating amino acid based substrates comprising a protected thiol compound having the formula R—(S—Pr)m where R is a functional group, S is sulfur, and Pr is a heterocyclic protecting group, and m is an integer between 1 and 100. The invention further relates to systems which comprise this protected thiol compound and an activating mechanism. The protected thiol compounds of the present invention may be used in hair care compositions, textile care compositions, cosmetic compositions, oral care compositions, skin care, nail care, laundry care, acne care and animal care compositions. Preferred embodiments of the present invention provide a modified UV absorber and a modified antioxidant, methods for making them and compositions conprising them.
- -
-
-
- Topical compositions comprising protected functional thiols
-
This invention relates to a topical composition for treating amino acid based substrates comprising a protected thiol compound having the formula R—(S—Pr) m where R is a functional group, S is sulfur, and Pr is a heterocyclic protecting group, and m is an integer between 1 and 100. The invention further relates to systems which comprise this protected thiol compound and an activating mechanism. The protected thiol compounds of the present invention may be used in hair care compositions, textile care compositions, cosmetic compositions, oral care compositions, skin care, nail care, laundry care, acne care and animal care compositions. Preferred embodiments of the present invention provide a modified UV absorber and a modified antioxidant, methods for making them and compositions conprising them.
- -
-
-
- A mild, convenient synthesis of sulfinic acid salts and sulfonamides from alkyl and aryl halides
-
A general, mild, and convenient method has been developed for the synthesis of various alkyl and aryl sulfinic acid salts and sulfonamides from the corresponding halides. Key to the success of this methodology is the design and facile synthesis of sodium 3-methoxy-3-oxopropane-1-sulfinate (SMOPS), a reagent that serves to introduce the protected sulfinate moiety directly to the substrate, thus avoiding the use of oxidizing and other harsh reaction conditions such as organolithium or Grignard reagents. Many functional groups, as well as heterocycles, are tolerated in the sequence.
- Baskin, Jeremy M,Wang, Zhaoyin
-
p. 8479 - 8483
(2007/10/03)
-
- HETEROCYCLIC THROMBIN INHIBITORS
-
Heterocyclic thrombin inhibitors are provided which have the structure STR1 wherein n, R, R 1, R 2, R 3, G, G x, R. sup.6', Ra, Xa, R 6, Rb, R 3, p, Q, A and R 4 are as defined herein.
- -
-
-
- Quinoxaline compounds, their preparation and use
-
From EXEMP_CLAIMS : 1. Quinoxaline compounds having the formula I wherein R1 is hydrogen, NO2, CN, CF3 or halogen, R2 and R3 independently are hydrogen, CN, CF3, halogen, C(NOH)C1-6-alkyl, COR4 or SO2R4, wherein R4 is C1-6-alkyl, optionally substituted with CONH2, or NR5R6, wherein R5, R6 independently are hydrogen, C3-6-cycloalkyl, C1-6-alkyl optionally substituted with CONH2 or 2-oxo-pyrrolidinyl, or pharmaceutically acceptable salts thereof.
- -
-
-
- Mild and Efficient Synthesis of Aromatic Sulfonamides by in situ Preparation of the Corresponding Sulfonyl Isothiocyanates
-
A new reaction between chlorosulfonyl isocyanate (1) and trialkylstannyl-substituted arenes 2a-k, 7, 9 is described.It provides the aromatic sulfonyl isocyanates 3 or their derivatives, the sulfonamides 4a-j, the sulfonylcarbamates 5a-b, or sulfonylureas 6, respectively.The trialkylstannyl group as an efficient leaving group allows mild reaction conditions to be applied and unusual substitution patterns to be obtained, normally not accessible by electrophilic aromatic substitutions.Thus, sulfonamidation can be achieved in meta position to a trifluoromethyl group. Key words: Electrophilic aromatic substitution; sulfodestannalytion; isocyanates, sulfonyl, aromatic; sulfonyl compounds; trialkylarylstannanes, application of
- Arnswald, Martin,Neumann, Wilhelm P.
-
p. 1997 - 2000
(2007/10/02)
-
- PEPTIDE DERIVATIVES
-
The invention concerns pharmaceutically useful trifluoromethyl ketone substituted di-, tri-and tetra-peptide derivatives of the formulae Ia, Ib, Ic set out hereinafter, and salts thereof, which are inhibitors of human leukocyte elastase. Also described herein are pharmaceutical compositions containing a peptide derivative and processes and intermediates for use in the manufacture of the peptide derivatives.
- -
-
-
- The Electrostatically Paired Bis(dimethyl sulfoxide)(tetrakis(1-methylpyridinium-4-yl)porphinato)iron(III)/(4,4',4'',4'''-Tetrasulfonatophthalocyaninato)zinc(II) System. Solution Structure and Dynamics
-
The electrostatic pairing interactions between the bis(dimethyl sulfoxide)(tetrakis(1-methylpyridinium-4-yl)porphinato)iron(III) cation, 5+, and the (4,4',4'',4'''-tetrasulfonatophthalocyaninato)zinc(II) anion, 4-, have been studied in dimethyl sulfoxide (DMSO) solution.Measurements of the electrostatic pair association constant, Kep, and its dependence upon ionic strength (Me4NClO4) were made with standard visible spectroscopic techniques while association dynamics were studied by NMR methods in DMSO-d6 solution.The exchange rate lawfor electrostatic pair formation takes into account DMSO solvent exchange of the iron porphyrin-solvent complex, and the exchange lifetime for the pair at ionic strength of 1 mM is calculated to be ca. 0.24 s at 25 deg C.Solution structural assessments were made by using measurements of the intermolecular dipolar relaxation of the (tetrasulfonatophthalocyaninato)zinc(II) protons due to the paramagnetic high-spin iron(III) center in the electrostatic pair.The structural model developed permitted calculation of a set of possible iron positions with respect to the phthalocyanine plane which are consistent with a cofacial dimeric structure displaying ?-? interactions due to pyrrole ring overlap.
- Goodwin, John A.,Scheidt, W. Robert
-
p. 4432 - 4439
(2007/10/02)
-
- Herbicidal sulfonamides
-
N-(heterocyclicaminocarbonyl)arylsulfonamides, such as N-[(4,6-dimethylpyrimidin-2-yl)aminocarbonyl] benzenesulfonamide, are useful for the regulation of plant growth and as herbicides, particularly for controlling nutsedge.
- -
-
-