3D-QSAR and Docking Studies on Pyrimidine Derivatives as CSF-1R Inhibitors

2020 ◽  
Vol 17 (3) ◽  
pp. 341-355
Author(s):  
Ya-ting Deng ◽  
Jun-wei Wang ◽  
Han Chu ◽  
Juan Wang ◽  
Yong Hu ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
3D Qsar ◽  
Docking Studies ◽  
Colony Stimulating Factor ◽  
Training Set ◽  
Pyrimidine Derivatives ◽  
Comfa Model ◽  
Inhibitory Activities ◽  
The Relationship ◽  
Stimulating Factor

Background: Colony Stimulating Factor-1 Receptor (CSF-1R) is associated with malignancy, invasiveness and poor prognosis of tumors, and pyrimidine derivatives are considered as a novel class of CSF-1R inhibitor. Methods: To explore the relationship between the structures of substituted pyrimidine derivatives and their inhibitory activities against CSF-1R, CoMFA and CoMSIA analyses, and molecular docking studies were performed on a dataset of forty-four compounds. Results: We found in CoMFA model including steric and electrostatic fields for the training set, the cross-validated q2 value was 0.617 and the non-cross-validated r2 value was 0.983. While, the crossvalidated q2 value was 0.637 and the non-cross-validated r2 value was 0.984 in CoMSIA Model which include steric, electrostatic and hydrophobic fields. 3D equipotential maps generated from CoMFA and CoMSIA along with the docking binding structures provided enough information about the structural requirements for better activity. Conclusion: The data generated from the present study helped us to predict the activity of new inhibitors and further design some novel and potent CSF-1R inhibitors.

3D-QSAR and Docking Studies of Pyrido[2,3-d]pyrimidine Derivatives as Wee1 Inhibitors

2012 ◽  
Vol 25 (3) ◽  
pp. 297-307 ◽  
Author(s):  
Guo-hua Zeng ◽  
Wen-juan Wu ◽  
Rong Zhang ◽  
Jun Sun ◽  
Wen-guo Xie ◽  
...  
Keyword(s):  
3D Qsar ◽  
Docking Studies ◽  
Pyrimidine Derivatives

scholarly journals Close Association between Clearance of Recombinant Human Granulocyte Colony-Stimulating Factor (G-CSF) and G-CSF Receptor on Neutrophils in Cancer Patients

1999 ◽  
Vol 43 (1) ◽  
pp. 21-24 ◽  
Author(s):  
Kenji Terashi ◽  
Mikio Oka ◽  
Shigehiro Ohdo ◽  
Taku Furukubo ◽  
Chizuko Ikeda ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Bolus Dose ◽  
Close Association ◽  
Inverse Correlation ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Csf Levels ◽  
Chemotherapy Induced Neutropenia ◽  
The Relationship ◽  
Stimulating Factor

ABSTRACT Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is used to counter chemotherapy-induced neutropenia. Our previous study showed an inverse correlation between serum rhG-CSF levels and the number of circulating neutrophils in cancer patients (H. Takatani, H. Soda, M. Fukuda, M. Watanabe, A. Kinoshita, T. Nakamura, and M. Oka, Antimicrob. Agents Chemother. 40:988–991, 1996). The aim of this study was to clarify the relationship between rhG-CSF clearance and G-CSF receptors on circulating neutrophils. In five cancer patients receiving chemotherapy, a bolus dose of rhG-CSF (5 μg/kg) was injected intravenously during defined phases of posttreatment neutropenia and neutrophilia. Serum rhG-CSF levels were measured by a chemiluminescence enzyme immunoassay and analyzed by moment analysis. G-CSF receptors on neutrophils were detected by flow cytometry with biotinylated rhG-CSF. rhG-CSF clearance was significantly higher at neutrophilia than at neutropenia (1,497 ± 132 versus 995 ± 266 ml/h; P < 0.01). The percentage of G-CSF receptor-positive neutrophils, reflecting the number of G-CSF receptors per cell, was low at neutropenia without rhG-CSF therapy (44.5% ± 22.1%) and high at neutrophilia with rhG-CSF therapy (73.0% ± 11.4%; P < 0.01). rhG-CSF clearance closely correlated with the percentage of G-CSF receptor-positive neutrophils (r 2 = 0.91; P < 0.0001) and neutrophil count (r 2 = 0.72; P < 0.005). Our results indicate that, in cancer patients receiving chemotherapy, rhG-CSF increases the number of G-CSF receptors per cell as well as circulating neutrophil counts, resulting in modulation of its own clearance.

Progenitor-cell mobilization after low-dose cyclophosphamide and granulocyte colony-stimulating factor: an analysis of progenitor-cell quantity and quality and factors predicting for these parameters in 101 pretreated patients with malignant lymphoma.

1997 ◽  
Vol 15 (2) ◽  
pp. 535-546 ◽  
Author(s):  
M J Watts ◽  
A M Sullivan ◽  
E Jamieson ◽  
R Pearce ◽  
A Fielding ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Cell Number ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Platelet Recovery ◽  
Neutrophil Recovery ◽  
Cell Mobilization ◽  
Wbc Count ◽  
The Relationship ◽  
Stimulating Factor

PURPOSE To define parameters that predict for rapid engraftment after peripheral-blood stem-cell (PBSC) transplantation, progenitor thresholds, the proportion of patients who achieve these thresholds with a standardized mobilization regimen, and the factors that predict for mobilization efficiency. PATIENTS AND METHODS One hundred and one patients with pretreated lymphoma were mobilized with cyclophosphamide 1.5 g/m2 and granulocyte colony-stimulating factor (G-CSF), with the first apheresis performed when the recovery WBC count was > or = 5.0 x 10(9)/L. The relationship between the number of progenitor cells collected and patient age, sex, diagnosis, prior radiotherapy, and time since last chemotherapy was determined by multivariate analysis. The relationship between these factors, progenitor numbers returned, post-PBSC G-CSF, and hematologic recovery was performed in 81 patients following chemotherapy with carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM protocol). RESULTS No BEAM recipients had delayed neutrophil recovery beyond 28 days. Delayed platelet recovery occurred in 7.4% and minimum and optimum thresholds of 1 x 10(6) and 3.5 x 10(6) CD34+ cells/kg and 1 x 10(5) and 3.5 x 10(5) granulocyte-macrophage colony-forming cells (GM-CFC)/kg were established. Hematologic recovery was adversely affected by prior treatment with mini-BEAM, and neutrophil recovery was accelerated by post-PBSC G-CSF. The minimum GM-CFC threshold was achieved with a single apheresis in 83% of patients and in 90% with two aphereses. The optimal threshold was achieved with two leukaphereses in 69% of patients. Prior radiotherapy adversely affected mobilization. CONCLUSION Hematopoietic recovery following PBSC is dependent on progenitor-cell number infused and affect of previous chemotherapy on progenitor quality. Progenitor-cell mobilization is adversely affected by prior radiotherapy. The minimum threshold of GM-CFC required is achieved in most patients with a single apheresis, but an optimal collection usually requires at least two harvests.

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