Tag: 308.3131

A novel GSK-3 inhibitor binds to GSK-3尾 via a reversible, time and Cys-199-dependent mechanism was written by Ghazanfari, Davoud;Noori, Mahboubeh S.;Bergmeier, Stephen C.;Hines, Jennifer V.;McCall, Kelly D.;Goetz, Douglas J.. And the article was included in Bioorganic & Medicinal Chemistry in 2021.SDS of cas: 487021-52-3 This article mentions the following:

Glycogen synthase kinase-3 (GSK-3) has been implicated in numerous pathologies making GSK-3 an attractive therapeutic target. Our group has identified a compound termed COB-187 that is a potent and selective inhibitor of GSK-3. In this study, we probed the mechanism by which COB-187 inhibits GSK-3尾. Progress curves, generated via real-time monitoring of kinase activity, indicated that COB-187 inhibition of GSK-3尾 is time-dependent and subsequent jump dilution assays revealed that COB-187 binding to GSK-3尾 is reversible. Further, a plot of the kinetic constant (kobs) vs. COB-187 concentration suggested that, within the range of concentrations studied, COB-187 binds to GSK-3尾 via an induced-fit mechanism. There is a critical cysteine residue at the entry to the active site of GSK-3尾 (Cys-199). We generated a mutant version of GSK-3尾 wherein Cys-199 was substituted with an alanine. This mutation caused a dramatic decrease in the activity of COB-187; specifically, an IC50 in the nM range for wild type vs. >100渭M for the mutant. A screen of COB-187 against 34 kinases that contain a conserved cysteine in their active site revealed that COB-187 is highly selective for GSK-3 indicating that COB-187s inhibition of GSK-3尾 via Cys-199 is specific. Combined, these findings suggest that COB-187 inhibits GSK-3尾 via a specific, reversible, time and Cys-199-dependent mechanism. In the experiment, the researchers used many compounds, for example, 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3SDS of cas: 487021-52-3).

1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3) belongs to thiazole derivatives. The higher aromaticity of thiazole is due to delocalization of a lone pair of sulfur electrons across the ring, which is evidenced by chemical shifts of ring hydrogen at 未 7.27 and 8.77 ppm (C2 and C4), indicating diamagnetic ring current. Thiazole is a versatile building block for the construction and lead generation of new drug discoveries. Numerous diazole-based compounds are in clinical use as anticancer, antileukemic, antiinflammatory, antiviral, antifungal, antirheumatic, immunomodulator, and antiparasitic agents.SDS of cas: 487021-52-3

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Kinase inhibitor profile for human Nek1, Nek6, and Nek7 and analysis of the structural basis for inhibitor specificity was written by Moraes, Eduardo Cruz;Meirelles, Gabriela Vaz;Honorato, Rodrigo Vargas;Brasil de Souza, Tatiana de Arruda Campos;Elisa de Souza, Edmarcia;Murakami, Mario Tyago;Lopes de Oliveira, Paulo Sergio;Kobarg, Jorg. And the article was included in Molecules in 2015.Application In Synthesis of 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea This article mentions the following:

Human Neks are a conserved protein kinase family related to cell cycle progression and cell division and are considered potential drug targets for the treatment of cancer and other pathologies. We screened the activation loop mutant kinases hNek1 and hNek2, wild-type hNek7, and five hNek6 variants in different activation/phosphorylation statesand compared them against 85 compounds using thermal shift denaturation. We identified three compounds with significant Tm shifts: JNK Inhibitor II for hNek1(螖262-1258)-(T162A), Isogranulatimide for hNek6(S206A), andGSK-3 Inhibitor XIII for hNek7wt. Each one of these compounds was also validated by reducing the kinases activity by at least 25%. The binding sites for these compounds were identified by in silico docking at the ATP-binding site of the resp. hNeks. Potential inhibitors were first screened by thermal shift assays, had their efficiency tested by a kinase assay, and were finally analyzed by mol. docking. Our findings corroborate the idea of ATP-competitive inhibition for hNek1 and hNek6 and suggest a novel non-competitive inhibition for hNek7 in regard to GSK-3 Inhibitor XIII. Our results demonstrate that our approach is useful for finding promising general and specific hNekscandidate inhibitors, which may also function as scaffolds to design more potent and selective inhibitors. In the experiment, the researchers used many compounds, for example, 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3Application In Synthesis of 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea).

1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3) belongs to thiazole derivatives. The higher aromaticity of thiazole is due to delocalization of a lone pair of sulfur electrons across the ring, which is evidenced by chemical shifts of ring hydrogen at 未 7.27 and 8.77 ppm (C2 and C4), indicating diamagnetic ring current. There are numerous natural products that possess a thiazole ring with broad pharmacological activities. Thiamine, also known as vitamin B1, possesses a thiazole ring linked with 2-methylpyrimidine-4-amine as hydrochloride salt.Application In Synthesis of 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Delayed re-endothelialization with rapamycin-coated stents is rescued by the addition of a glycogen synthase kinase-3尾 inhibitor was written by Ma, Xiaoli;Hibbert, Benjamin;Dhaliwal, Bharbhoor;Seibert, Tara;Chen, Yong-Xiang;Zhao, Xiaoling;O’Brien, Edward R.. And the article was included in Cardiovascular Research in 2010.COA of Formula: C12H12N4O4S This article mentions the following:

Aims: Drug-eluting stents (DESs) reduce neointima area and in-stent restenosis but delay re-endothelialization. Recently, we demonstrated that pharmacol. expansion and functional enhancement of endothelial progenitor cells (EPCs) can be achieved by treatment with a glycogen synthase kinase-3尾 inhibitor (GSKi)-even for feeble cells derived from coronary artery disease patients. GSKi treatment enhanced EPC adhesion via up-regulated expression of the 伪-4 integrin, ameliorated re-endothelialization, and reduced neointima formation in denuded murine arteries. Hence, we hypothesized that GSKi-coated stents (GSs) will enhance EPC adhesion and attenuate delayed vascular healing associated with rapamycin, a key DES agent. Methods and results: In vitro human EPCs adhered to GS with affinities that were 2脳, 14脳, and 13脳 greater than vehicle (VSs)-, rapamycin (RSs)-, and rapamycin plus GSKi (RGSs)-coated stents, resp. Stents were inserted in rabbit carotid arteries, and at 14 days, neointima area was 45 and 49% lower in GSs compared with bare metal stents (BMSs) and VSs. Moreover, RSs had a 47% larger neointima area than GSs, but RGSs reduced neointima area to a level comparable to GSs. Seven days after stenting, GSs displayed re-endothelialization that was 40, 33, and 42% greater than BMSs, VSs, and RSs, resp. Moreover, RGSs had 41% more re-endothelialization than RSs. At 14 days, the 7-day re-endothelialization patterns persisted. Conclusion: GSKi efficiently ameliorates the vascular response to stent implantation and has an important redeeming effect on the deleterious endothelial effects of rapamycin-coated stents. In the experiment, the researchers used many compounds, for example, 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3COA of Formula: C12H12N4O4S).

1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. Thiazole is a versatile building block for the construction and lead generation of new drug discoveries. Numerous diazole-based compounds are in clinical use as anticancer, antileukemic, antiinflammatory, antiviral, antifungal, antirheumatic, immunomodulator, and antiparasitic agents.COA of Formula: C12H12N4O4S

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Delayed re-endothelialization with rapamycin-coated stents is rescued by the addition of a glycogen synthase kinase-3β inhibitor was written by Ma, Xiaoli;Hibbert, Benjamin;Dhaliwal, Bharbhoor;Seibert, Tara;Chen, Yong-Xiang;Zhao, Xiaoling;O’Brien, Edward R.. And the article was included in Cardiovascular Research in 2010.COA of Formula: C12H12N4O4S This article mentions the following:

Aims: Drug-eluting stents (DESs) reduce neointima area and in-stent restenosis but delay re-endothelialization. Recently, we demonstrated that pharmacol. expansion and functional enhancement of endothelial progenitor cells (EPCs) can be achieved by treatment with a glycogen synthase kinase-3β inhibitor (GSKi)-even for feeble cells derived from coronary artery disease patients. GSKi treatment enhanced EPC adhesion via up-regulated expression of the α-4 integrin, ameliorated re-endothelialization, and reduced neointima formation in denuded murine arteries. Hence, we hypothesized that GSKi-coated stents (GSs) will enhance EPC adhesion and attenuate delayed vascular healing associated with rapamycin, a key DES agent. Methods and results: In vitro human EPCs adhered to GS with affinities that were 2×, 14×, and 13× greater than vehicle (VSs)-, rapamycin (RSs)-, and rapamycin plus GSKi (RGSs)-coated stents, resp. Stents were inserted in rabbit carotid arteries, and at 14 days, neointima area was 45 and 49% lower in GSs compared with bare metal stents (BMSs) and VSs. Moreover, RSs had a 47% larger neointima area than GSs, but RGSs reduced neointima area to a level comparable to GSs. Seven days after stenting, GSs displayed re-endothelialization that was 40, 33, and 42% greater than BMSs, VSs, and RSs, resp. Moreover, RGSs had 41% more re-endothelialization than RSs. At 14 days, the 7-day re-endothelialization patterns persisted. Conclusion: GSKi efficiently ameliorates the vascular response to stent implantation and has an important redeeming effect on the deleterious endothelial effects of rapamycin-coated stents. In the experiment, the researchers used many compounds, for example, 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3COA of Formula: C12H12N4O4S).

1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. Thiazole is a versatile building block for the construction and lead generation of new drug discoveries. Numerous diazole-based compounds are in clinical use as anticancer, antileukemic, antiinflammatory, antiviral, antifungal, antirheumatic, immunomodulator, and antiparasitic agents.COA of Formula: C12H12N4O4S

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

A novel GSK-3 inhibitor binds to GSK-3β via a reversible, time and Cys-199-dependent mechanism was written by Ghazanfari, Davoud;Noori, Mahboubeh S.;Bergmeier, Stephen C.;Hines, Jennifer V.;McCall, Kelly D.;Goetz, Douglas J.. And the article was included in Bioorganic & Medicinal Chemistry in 2021.SDS of cas: 487021-52-3 This article mentions the following:

Glycogen synthase kinase-3 (GSK-3) has been implicated in numerous pathologies making GSK-3 an attractive therapeutic target. Our group has identified a compound termed COB-187 that is a potent and selective inhibitor of GSK-3. In this study, we probed the mechanism by which COB-187 inhibits GSK-3β. Progress curves, generated via real-time monitoring of kinase activity, indicated that COB-187 inhibition of GSK-3β is time-dependent and subsequent jump dilution assays revealed that COB-187 binding to GSK-3β is reversible. Further, a plot of the kinetic constant (kobs) vs. COB-187 concentration suggested that, within the range of concentrations studied, COB-187 binds to GSK-3β via an induced-fit mechanism. There is a critical cysteine residue at the entry to the active site of GSK-3β (Cys-199). We generated a mutant version of GSK-3β wherein Cys-199 was substituted with an alanine. This mutation caused a dramatic decrease in the activity of COB-187; specifically, an IC50 in the nM range for wild type vs. >100μM for the mutant. A screen of COB-187 against 34 kinases that contain a conserved cysteine in their active site revealed that COB-187 is highly selective for GSK-3 indicating that COB-187s inhibition of GSK-3β via Cys-199 is specific. Combined, these findings suggest that COB-187 inhibits GSK-3β via a specific, reversible, time and Cys-199-dependent mechanism. In the experiment, the researchers used many compounds, for example, 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3SDS of cas: 487021-52-3).

1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3) belongs to thiazole derivatives. The higher aromaticity of thiazole is due to delocalization of a lone pair of sulfur electrons across the ring, which is evidenced by chemical shifts of ring hydrogen at δ 7.27 and 8.77 ppm (C2 and C4), indicating diamagnetic ring current. Thiazole is a versatile building block for the construction and lead generation of new drug discoveries. Numerous diazole-based compounds are in clinical use as anticancer, antileukemic, antiinflammatory, antiviral, antifungal, antirheumatic, immunomodulator, and antiparasitic agents.SDS of cas: 487021-52-3

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Kinase inhibitor profile for human Nek1, Nek6, and Nek7 and analysis of the structural basis for inhibitor specificity was written by Moraes, Eduardo Cruz;Meirelles, Gabriela Vaz;Honorato, Rodrigo Vargas;Brasil de Souza, Tatiana de Arruda Campos;Elisa de Souza, Edmarcia;Murakami, Mario Tyago;Lopes de Oliveira, Paulo Sergio;Kobarg, Jorg. And the article was included in Molecules in 2015.Application In Synthesis of 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea This article mentions the following:

Human Neks are a conserved protein kinase family related to cell cycle progression and cell division and are considered potential drug targets for the treatment of cancer and other pathologies. We screened the activation loop mutant kinases hNek1 and hNek2, wild-type hNek7, and five hNek6 variants in different activation/phosphorylation statesand compared them against 85 compounds using thermal shift denaturation. We identified three compounds with significant Tm shifts: JNK Inhibitor II for hNek1(Δ262-1258)-(T162A), Isogranulatimide for hNek6(S206A), andGSK-3 Inhibitor XIII for hNek7wt. Each one of these compounds was also validated by reducing the kinases activity by at least 25%. The binding sites for these compounds were identified by in silico docking at the ATP-binding site of the resp. hNeks. Potential inhibitors were first screened by thermal shift assays, had their efficiency tested by a kinase assay, and were finally analyzed by mol. docking. Our findings corroborate the idea of ATP-competitive inhibition for hNek1 and hNek6 and suggest a novel non-competitive inhibition for hNek7 in regard to GSK-3 Inhibitor XIII. Our results demonstrate that our approach is useful for finding promising general and specific hNekscandidate inhibitors, which may also function as scaffolds to design more potent and selective inhibitors. In the experiment, the researchers used many compounds, for example, 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3Application In Synthesis of 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea).

1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3) belongs to thiazole derivatives. The higher aromaticity of thiazole is due to delocalization of a lone pair of sulfur electrons across the ring, which is evidenced by chemical shifts of ring hydrogen at δ 7.27 and 8.77 ppm (C2 and C4), indicating diamagnetic ring current. There are numerous natural products that possess a thiazole ring with broad pharmacological activities. Thiamine, also known as vitamin B1, possesses a thiazole ring linked with 2-methylpyrimidine-4-amine as hydrochloride salt.Application In Synthesis of 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Delayed re-endothelialization with rapamycin-coated stents is rescued by the addition of a glycogen synthase kinase-3β inhibitor was written by Ma, Xiaoli;Hibbert, Benjamin;Dhaliwal, Bharbhoor;Seibert, Tara;Chen, Yong-Xiang;Zhao, Xiaoling;O’Brien, Edward R.. And the article was included in Cardiovascular Research in 2010.COA of Formula: C12H12N4O4S This article mentions the following:

Aims: Drug-eluting stents (DESs) reduce neointima area and in-stent restenosis but delay re-endothelialization. Recently, we demonstrated that pharmacol. expansion and functional enhancement of endothelial progenitor cells (EPCs) can be achieved by treatment with a glycogen synthase kinase-3β inhibitor (GSKi)-even for feeble cells derived from coronary artery disease patients. GSKi treatment enhanced EPC adhesion via up-regulated expression of the α-4 integrin, ameliorated re-endothelialization, and reduced neointima formation in denuded murine arteries. Hence, we hypothesized that GSKi-coated stents (GSs) will enhance EPC adhesion and attenuate delayed vascular healing associated with rapamycin, a key DES agent. Methods and results: In vitro human EPCs adhered to GS with affinities that were 2×, 14×, and 13× greater than vehicle (VSs)-, rapamycin (RSs)-, and rapamycin plus GSKi (RGSs)-coated stents, resp. Stents were inserted in rabbit carotid arteries, and at 14 days, neointima area was 45 and 49% lower in GSs compared with bare metal stents (BMSs) and VSs. Moreover, RSs had a 47% larger neointima area than GSs, but RGSs reduced neointima area to a level comparable to GSs. Seven days after stenting, GSs displayed re-endothelialization that was 40, 33, and 42% greater than BMSs, VSs, and RSs, resp. Moreover, RGSs had 41% more re-endothelialization than RSs. At 14 days, the 7-day re-endothelialization patterns persisted. Conclusion: GSKi efficiently ameliorates the vascular response to stent implantation and has an important redeeming effect on the deleterious endothelial effects of rapamycin-coated stents. In the experiment, the researchers used many compounds, for example, 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3COA of Formula: C12H12N4O4S).

1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. Thiazole is a versatile building block for the construction and lead generation of new drug discoveries. Numerous diazole-based compounds are in clinical use as anticancer, antileukemic, antiinflammatory, antiviral, antifungal, antirheumatic, immunomodulator, and antiparasitic agents.COA of Formula: C12H12N4O4S

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica