Tag: 406.4824

Dorsomorphin and LDN-193189 inhibit BMP-mediated Smad, p38 and Akt signalling in C2C12 cells was written by Boergermann, J. H.;Kopf, J.;Yu, P.-B.;Knaus, P.. And the article was included in International Journal of Biochemistry & Cell Biology in 2010.Computed Properties of C25H22N6 This article mentions the following:

Bone morphogenetic proteins (BMPs) are key regulators of cell fate decisions during embryogenesis and tissue homeostasis. BMPs signal through a coordinated assembly of two types of transmembrane serine/threonine kinase receptors to induce Smad1/5/8 plus non-Smad pathways, such as MAPK and Akt. The recent discovery of BMP receptor inhibitors opened new avenues to study specific BMP signaling and to delineate this effect from TGF-尾 and Activin signaling. Here we present comprehensive and quant. analyses on both canonical and non-Smad mediated BMP signaling under Dorsomorphin (DM) and LDN-193189 (LDN) treatment conditions. We demonstrate for the first time, that both compounds affect not only the Smad but also the non-Smad signaling pathways induced by either BMP2, BMP6 or GDF5. The activation of p38, ERK1/2 and Akt in C2C12 cells was inhibited by DM and LDN. In addition “off-target” effects on all branches of BMP non-Smad signaling are presented. From this we conclude that the inhibition of BMP receptors by DM and more efficiently by LDN-193189 affects all known BMP induced signaling cascades. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Computed Properties of C25H22N6).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Computed Properties of C25H22N6

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Identification and characterization of teratogenic chemicals using embryonic stem cells isolated from a wnt/β-catenin-reporter transgenic mouse line was written by Kugler, Josephine;Kemler, Rolf;Luch, Andreas;Oelgeschlaeger, Michael. And the article was included in Toxicological Sciences in 2016.Recommanded Product: 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline This article mentions the following:

Embryonic stem cells (ESCs) are commonly used for the anal. of gene function in embryonic development and provide valuable models for human diseases. In recent years, ESCs have also become an attractive tool for toxicol. testing, in particular for the identification of teratogenic compounds The authors have recently described a Bmp-reporter ESC line as a new tool to identify teratogenic compounds and to characterize the mol. mechanisms mediating embryonic toxicity. Here the authors describe the use of a Wnt/β-Catenin-reporter ESC line isolated from a previously described mouse line that carries the LacZ reporter gene under the control of a β-Catenin responsive promoter. The reporter ESC line stably differentiates into cardiomyocytes within 12 days. The reporter was endogenously induced between day 3-5 of differentiation reminiscent of its expression in vivo, in which strong LacZ activity is detected around gastrulation. Subsequently its expression becomes restricted to mesodermal cells and cells undergoing an epithelial to mesenchymal transition. The Wnt/β-Catenin-dependent expression of the reporter protein allowed quantification of dose- and time-dependent effects of teratogenic chems. In particular, valproic acid reduced reporter activity on day 7, whereas retinoic acid induced reporter activity on day 5 at concentrations comparable to the ones inhibiting the formation of functional cardiomyocytes, the classical read-out of the embryonic stem cell test (EST). In addition, the authors were also able to show distinct effects of teratogenic chems. on the Wnt/β-Catenin-reporter compared with the previously described Bmp-reporter ESCs. Thus, different reporter cell lines provide complementary tools for the identification and anal. of potentially teratogenic compounds In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Recommanded Product: 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Recommanded Product: 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Uncovering molecular bases underlying bone morphogenetic protein receptor inhibitor selectivity was written by Alsamarah, Abdelaziz;LaCuran, Alecander E.;Oelschlaeger, Peter;Hao, Jijun;Luo, Yun. And the article was included in PLoS One in 2015.Computed Properties of C25H22N6 This article mentions the following:

Abnormal alteration of bone morphogenetic protein (BMP) signaling is implicated in many types of diseases including cancer and heterotopic ossifications. Hence, small mols. targeting BMP type I receptors (BMPRI) to interrupt BMP signaling are believed to be an effective approach to treat these diseases. However, lack of understanding of the mol. determinants responsible for the binding selectivity of current BMP inhibitors has been a big hindrance to the development of BMP inhibitors for clin. use. To address this issue, we carried out in silico experiments to test whether computational methods can reproduce and explain the high selectivity of a small mol. BMP inhibitor DMH1 on BMPRI kinase ALK2 vs. the closely related TGF-β type I receptor kinase ALK5 and vascular endothelial growth factor receptor type 2 (VEGFR2) tyrosine kinase. We found that, while the rigid docking method used here gave nearly identical binding affinity scores among the three kinases; free energy perturbation coupled with Hamiltonian replica-exchange mol. dynamics (FEP/H-REMD) simulations reproduced the absolute binding free energies in excellent agreement with exptl. data. Furthermore, the binding poses identified by FEP/HREMD led to a quant. anal. of phys./chem. determinants governing DMH1 selectivity. The current work illustrates that small changes in the binding site residue type (e.g. pre-hinge region in ALK2 vs. ALK5) or side chain orientation (e.g. Tyr219 in caALK2 vs. wtALK2), as well as a subtle structural modification on the ligand (e.g. DMH1 vs. LDN193189) will cause distinct binding profiles and selectivity among BMP inhibitors. Therefore, the current computational approach represents a new way of investigating BMP inhibitors. Our results provide critical information for designing exclusively selective BMP inhibitors for the development of effective pharmacotherapy for diseases caused by aberrant BMP signaling. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Computed Properties of C25H22N6).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Computed Properties of C25H22N6

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Dorsomorphin and LDN-193189 inhibit BMP-mediated Smad, p38 and Akt signalling in C2C12 cells was written by Boergermann, J. H.;Kopf, J.;Yu, P.-B.;Knaus, P.. And the article was included in International Journal of Biochemistry & Cell Biology in 2010.Computed Properties of C25H22N6 This article mentions the following:

Bone morphogenetic proteins (BMPs) are key regulators of cell fate decisions during embryogenesis and tissue homeostasis. BMPs signal through a coordinated assembly of two types of transmembrane serine/threonine kinase receptors to induce Smad1/5/8 plus non-Smad pathways, such as MAPK and Akt. The recent discovery of BMP receptor inhibitors opened new avenues to study specific BMP signaling and to delineate this effect from TGF-β and Activin signaling. Here we present comprehensive and quant. analyses on both canonical and non-Smad mediated BMP signaling under Dorsomorphin (DM) and LDN-193189 (LDN) treatment conditions. We demonstrate for the first time, that both compounds affect not only the Smad but also the non-Smad signaling pathways induced by either BMP2, BMP6 or GDF5. The activation of p38, ERK1/2 and Akt in C2C12 cells was inhibited by DM and LDN. In addition “off-target” effects on all branches of BMP non-Smad signaling are presented. From this we conclude that the inhibition of BMP receptors by DM and more efficiently by LDN-193189 affects all known BMP induced signaling cascades. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Computed Properties of C25H22N6).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Computed Properties of C25H22N6

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Identification and characterization of teratogenic chemicals using embryonic stem cells isolated from a wnt/β-catenin-reporter transgenic mouse line was written by Kugler, Josephine;Kemler, Rolf;Luch, Andreas;Oelgeschlaeger, Michael. And the article was included in Toxicological Sciences in 2016.Recommanded Product: 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline This article mentions the following:

Embryonic stem cells (ESCs) are commonly used for the anal. of gene function in embryonic development and provide valuable models for human diseases. In recent years, ESCs have also become an attractive tool for toxicol. testing, in particular for the identification of teratogenic compounds The authors have recently described a Bmp-reporter ESC line as a new tool to identify teratogenic compounds and to characterize the mol. mechanisms mediating embryonic toxicity. Here the authors describe the use of a Wnt/β-Catenin-reporter ESC line isolated from a previously described mouse line that carries the LacZ reporter gene under the control of a β-Catenin responsive promoter. The reporter ESC line stably differentiates into cardiomyocytes within 12 days. The reporter was endogenously induced between day 3-5 of differentiation reminiscent of its expression in vivo, in which strong LacZ activity is detected around gastrulation. Subsequently its expression becomes restricted to mesodermal cells and cells undergoing an epithelial to mesenchymal transition. The Wnt/β-Catenin-dependent expression of the reporter protein allowed quantification of dose- and time-dependent effects of teratogenic chems. In particular, valproic acid reduced reporter activity on day 7, whereas retinoic acid induced reporter activity on day 5 at concentrations comparable to the ones inhibiting the formation of functional cardiomyocytes, the classical read-out of the embryonic stem cell test (EST). In addition, the authors were also able to show distinct effects of teratogenic chems. on the Wnt/β-Catenin-reporter compared with the previously described Bmp-reporter ESCs. Thus, different reporter cell lines provide complementary tools for the identification and anal. of potentially teratogenic compounds In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Recommanded Product: 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Recommanded Product: 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Uncovering molecular bases underlying bone morphogenetic protein receptor inhibitor selectivity was written by Alsamarah, Abdelaziz;LaCuran, Alecander E.;Oelschlaeger, Peter;Hao, Jijun;Luo, Yun. And the article was included in PLoS One in 2015.Computed Properties of C25H22N6 This article mentions the following:

Abnormal alteration of bone morphogenetic protein (BMP) signaling is implicated in many types of diseases including cancer and heterotopic ossifications. Hence, small mols. targeting BMP type I receptors (BMPRI) to interrupt BMP signaling are believed to be an effective approach to treat these diseases. However, lack of understanding of the mol. determinants responsible for the binding selectivity of current BMP inhibitors has been a big hindrance to the development of BMP inhibitors for clin. use. To address this issue, we carried out in silico experiments to test whether computational methods can reproduce and explain the high selectivity of a small mol. BMP inhibitor DMH1 on BMPRI kinase ALK2 vs. the closely related TGF-β type I receptor kinase ALK5 and vascular endothelial growth factor receptor type 2 (VEGFR2) tyrosine kinase. We found that, while the rigid docking method used here gave nearly identical binding affinity scores among the three kinases; free energy perturbation coupled with Hamiltonian replica-exchange mol. dynamics (FEP/H-REMD) simulations reproduced the absolute binding free energies in excellent agreement with exptl. data. Furthermore, the binding poses identified by FEP/HREMD led to a quant. anal. of phys./chem. determinants governing DMH1 selectivity. The current work illustrates that small changes in the binding site residue type (e.g. pre-hinge region in ALK2 vs. ALK5) or side chain orientation (e.g. Tyr219 in caALK2 vs. wtALK2), as well as a subtle structural modification on the ligand (e.g. DMH1 vs. LDN193189) will cause distinct binding profiles and selectivity among BMP inhibitors. Therefore, the current computational approach represents a new way of investigating BMP inhibitors. Our results provide critical information for designing exclusively selective BMP inhibitors for the development of effective pharmacotherapy for diseases caused by aberrant BMP signaling. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Computed Properties of C25H22N6).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Computed Properties of C25H22N6

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Dorsomorphin and LDN-193189 inhibit BMP-mediated Smad, p38 and Akt signalling in C2C12 cells was written by Boergermann, J. H.;Kopf, J.;Yu, P.-B.;Knaus, P.. And the article was included in International Journal of Biochemistry & Cell Biology in 2010.Computed Properties of C25H22N6 This article mentions the following:

Bone morphogenetic proteins (BMPs) are key regulators of cell fate decisions during embryogenesis and tissue homeostasis. BMPs signal through a coordinated assembly of two types of transmembrane serine/threonine kinase receptors to induce Smad1/5/8 plus non-Smad pathways, such as MAPK and Akt. The recent discovery of BMP receptor inhibitors opened new avenues to study specific BMP signaling and to delineate this effect from TGF-β and Activin signaling. Here we present comprehensive and quant. analyses on both canonical and non-Smad mediated BMP signaling under Dorsomorphin (DM) and LDN-193189 (LDN) treatment conditions. We demonstrate for the first time, that both compounds affect not only the Smad but also the non-Smad signaling pathways induced by either BMP2, BMP6 or GDF5. The activation of p38, ERK1/2 and Akt in C2C12 cells was inhibited by DM and LDN. In addition “off-target” effects on all branches of BMP non-Smad signaling are presented. From this we conclude that the inhibition of BMP receptors by DM and more efficiently by LDN-193189 affects all known BMP induced signaling cascades. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Computed Properties of C25H22N6).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Computed Properties of C25H22N6

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Dorsomorphin and LDN-193189 inhibit BMP-mediated Smad, p38 and Akt signalling in C2C12 cells was written by Boergermann, J. H.;Kopf, J.;Yu, P.-B.;Knaus, P.. And the article was included in International Journal of Biochemistry & Cell Biology in 2010.Computed Properties of C25H22N6 This article mentions the following:

Bone morphogenetic proteins (BMPs) are key regulators of cell fate decisions during embryogenesis and tissue homeostasis. BMPs signal through a coordinated assembly of two types of transmembrane serine/threonine kinase receptors to induce Smad1/5/8 plus non-Smad pathways, such as MAPK and Akt. The recent discovery of BMP receptor inhibitors opened new avenues to study specific BMP signaling and to delineate this effect from TGF-β and Activin signaling. Here we present comprehensive and quant. analyses on both canonical and non-Smad mediated BMP signaling under Dorsomorphin (DM) and LDN-193189 (LDN) treatment conditions. We demonstrate for the first time, that both compounds affect not only the Smad but also the non-Smad signaling pathways induced by either BMP2, BMP6 or GDF5. The activation of p38, ERK1/2 and Akt in C2C12 cells was inhibited by DM and LDN. In addition “off-target” effects on all branches of BMP non-Smad signaling are presented. From this we conclude that the inhibition of BMP receptors by DM and more efficiently by LDN-193189 affects all known BMP induced signaling cascades. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Computed Properties of C25H22N6).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Computed Properties of C25H22N6

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics