scholarly journals Prodrugs for colon-restricted delivery: Design, synthesis, and in vivo evaluation of colony stimulating factor 1 receptor (CSF1R) inhibitors

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0203567 ◽  
Author(s):  
Dawn M. George ◽  
Raymond J. Huntley ◽  
Kevin Cusack ◽  
David B. Duignan ◽  
Michael Hoemann ◽  
...  
Keyword(s):  
Colony Stimulating Factor ◽  
In Vivo Evaluation ◽  
Design Synthesis ◽  
Stimulating Factor

scholarly journals Synthesis and Initial In Vivo Evaluation of [11C]AZ683—A Novel PET Radiotracer for Colony Stimulating Factor 1 Receptor (CSF1R)

2018 ◽  
Vol 11 (4) ◽  
pp. 136 ◽  
Author(s):  
Sean Tanzey ◽  
Xia Shao ◽  
Jenelle Stauff ◽  
Janna Arteaga ◽  
Phillip Sherman ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Radiochemical Purity ◽  
Colony Stimulating Factor ◽  
In Vivo Evaluation ◽  
Molar Activity ◽  
Positron Emission ◽  
New Strategy ◽  
Activity Yield ◽  
Stimulating Factor

Positron emission tomography (PET) imaging of Colony Stimulating Factor 1 Receptor (CSF1R) is a new strategy for quantifying both neuroinflammation and inflammation in the periphery since CSF1R is expressed on microglia and macrophages. AZ683 has high affinity for CSF1R (Ki = 8 nM; IC50 = 6 nM) and >250-fold selectivity over 95 other kinases. In this paper, we report the radiosynthesis of [11C]AZ683 and initial evaluation of its use in CSF1R PET. [11C]AZ683 was synthesized by 11C-methylation of the desmethyl precursor with [11C]MeOTf in 3.0% non-corrected activity yield (based upon [11C]MeOTf), >99% radiochemical purity and high molar activity. Preliminary PET imaging with [11C]AZ683 revealed low brain uptake in rodents and nonhuman primates, suggesting that imaging neuroinflammation could be challenging but that the radiopharmaceutical could still be useful for peripheral imaging of inflammation.

In vivo effects of macrophage colony-stimulating factor on human monocyte function

1991 ◽  
Vol 77 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Asim Khwaja ◽  
Beryl Johnson ◽  
Ian E. Addison ◽  
Kwee Yong ◽  
Karen Ruthven ◽  
...  
Keyword(s):  
Human Monocyte ◽  
Colony Stimulating Factor ◽  
Monocyte Function ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
In Vivo Effects ◽  
Stimulating Factor

Identification of tyrosine 706 in the kinase insert as the major colony-stimulating factor 1 (CSF-1)-stimulated autophosphorylation site in the CSF-1 receptor in a murine macrophage cell line

1990 ◽  
Vol 10 (6) ◽  
pp. 2991-3002
Author(s):  
P van der Geer ◽  
T Hunter
Keyword(s):  
Cell Line ◽  
Murine Macrophage ◽  
Colony Stimulating Factor ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Major Site ◽  
Murine Macrophage Cell Line ◽  
Stimulating Factor

The receptor for colony-stimulating factor 1 (CSF-1) is a ligand-activated protein-tyrosine kinase. It has been shown previously that the CSF-1 receptor is phosphorylated on serine in vivo and that phosphorylation on tyrosine can be induced by stimulation with CSF-1. We studied the phosphorylation of the CSF-1 receptor by using the BAC1.2F5 murine macrophage cell line, which naturally expresses CSF-1 receptors. Two-dimensional tryptic phosphopeptide mapping showed that the CSF-1 receptor is phosphorylated on several different serine residues in vivo. Stimulation with CSF-1 at 37 degrees C resulted in rapid phosphorylation on tyrosine at one major site and one or two minor sites. We identified the major site as Tyr-706. The identity of Tyr-706 was confirmed by mutagenesis. This residue is located within the kinase insert domain. There was no evidence that Tyr-973 (equivalent to Tyr-969 in the human CSF-1 receptor) was phosphorylated following CSF-1 stimulation. When cells were stimulated with CSF-1 at 4 degrees C, additional phosphotyrosine-containing phosphopeptides were detected and the level of phosphorylation of the individual phosphotyrosine-containing phosphopeptides was substantially increased. In addition, we show that CSF-1 receptors are capable of autophosphorylation at six to eight major sites in vitro.

N-pyridin-2-yl benzamide analogues as allosteric activators of glucokinase: Design, synthesis, in vitro,in silico and in vivo evaluation

2018 ◽  
Vol 93 (3) ◽  
pp. 364-372 ◽  
Author(s):  
Ajmer Singh Grewal ◽  
Rajeev Kharb ◽  
Deo Nandan Prasad ◽  
Jagdeep Singh Dua ◽  
Viney Lather
Keyword(s):  
In Silico ◽  
In Vivo Evaluation ◽  
Design Synthesis

scholarly journals A comparison of hematopoiesis in normal and splenectomized mice treated with granulocyte colony-stimulating factor

Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 563-569 ◽  
Author(s):  
G Molineux ◽  
Z Pojda ◽  
TM Dexter
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Extramedullary Hematopoiesis ◽  
High Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Response Data ◽  
Hematopoietic Precursor ◽  
Stimulating Factor

Abstract Recombinant human granulocyte colony-stimulating factor (rhG-CSF) induces leukocytosis in vivo in both intact and splenectomized mice. Full dose response data showed a plateau in this effect at doses over 500 micrograms rhG-CSF/kg body weight/d in intact mice. The effect is magnified in splenectomized mice, where leukocyte numbers reach 100 x 10(6) mL after 4 days' treatment at 250 micrograms/kg/d. Further hematopoietic precursor populations are also affected in both marrow and the spleen; in general, marrow parameters were depressed, while splenic populations were enlarged. In splenectomized mice, both blood- borne stem cells were enhanced, and foci of extramedullary hematopoiesis were enlarged in addition to the effects seen in intact mice. In the marrow of splenectomized and intact mice treated with a high dose of G-CSF, erythroid suppression in the marrow was confirmed with radioactive iron. Our studies confirm and extend previous work on the mode of action of G-CSF, and indicate that side effects of high dose G-CSF therapy might include erythroid suppression in the bone marrow.

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