In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml
Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)
Preparing Stock Solutions
Biological Activity
Description
Zoligratinib (Debio-1347, CH5183284, FF284) is a selective and orally available FGFR inhibitor with IC50 of 9.3 nM, 7.6 nM, 22 nM, and 290 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively. Phase 1.
Targets
FGFR2 (Cell-free assay)
FGFR1 (Cell-free assay)
FGFR3 (Cell-free assay)
FGFR4 (Cell-free assay)
7.6 nM
9.3 nM
22 nM
290 nM
In vitro
In cell-based assay, CH5183284 prevents autophosphorylation of FGFR1, FGFR2, and FGFR3 at 100 to 300 nM in the DMS114 (FGFR1 amplification), SNU-16 (FGFR2 amplification), and KMS11 [t(4;14) translocation and FGFR3 Y373C mutation] cell lines. CH5183284 thus produces selective antiproliferative activity against cancer cell lines harbouring genetic alterations in FGFR. CH5183284 also inhibit FGFR2 harbouring one type of the gatekeeper mutation (V564F) that causes resistance to other FGFR inhibitors.
In Vivo
CH5183284 (100 mg/kg/day, p.o.) shows selective and significant anti-tumour activity against xenografts with FGFR genetic alterations such as KG1 (leukaemia, FGFR1OP-FGFR1 fusion), SNU-16 (gastric cancer, FGFR2 amplification), MFE-280 (endometrial cancer, FGFR2 S252W mutation), UM-UC-14 (bladder cancer, FGFR3 S249C mutation), and RT112/84 (bladder cancer, FGFR3-TACC3 fusion).
The inhibitory activity of CH5183284/Debio 1347 against FGFR1 is evaluated using a radiometric filter assay by measuring the incorporation of 33Pi with a microplate scintillation counter. The phosphorylation activities of LCK, EGFR, KIT, MET, SRC, BRK, FGFR2, Flt3, LTK, INSR, YES, ABL, EPHA2, ZAP70, Fyn, IGF1R, KDR, and PDGFR on substrate peptides are determined by homogeneous time-resolved fluorescence assay with LANCE Eu-W1024 labelled anti-phosphotyrosine PT66 antibody according to standard methods. Time-resolved fluorescence is measured with an EnVision HTS microplate reader. The activities of Aurora A, Akt1/PKBα, PKA, Cdk1/cyclin B, Cdk2/cyclin A, PKCα, PKCβ1 and PKCβ2 on substrate peptides are determined by IMAP FP Screening Express Progressive Binding System. Fluorescence polarisation is measured with an EnVision HTS microplate reader.
The cell lines are added to the wells of 96-well plates containing 0.076 to 10,000 nM CH5183284/Debio 1347 and incubated at 37°C. After 4 days of incubation, Cell Counting Kit-8 solution is added and, after incubation for several more hours, absorbance at 450 nm is measured with the iMark Microplate-Reader. The antiproliferative activity is calculated using the formula (1 − T/C) × 100 (%), where T and C represent absorbance at 450 nm of the cells treated with drugs (T) and that of untreated control cells (C). The IC50 values are calculated using Microsoft Excel 2007.
Mice bearing KG1, SNU-16, MFE280, UM-UC-14, RT112/84, or MKN-45 tumors
Dosages
100 mg/kg/day
Administration
p.o.
References
https://pubmed.ncbi.nlm.nih.gov/25169980/
Sellecks Zoligratinib (Debio-1347) Has Been Cited by 12 Publications
Understanding and Overcoming Resistance to Selective FGFR inhibitors Across FGFR2-Driven Malignancies
[ Clin Cancer Res, 2024, 10.1158/1078-0432.CCR-24-1834]
Novel involvement of PLD-PKCδ-CREB axis in regulating FGF-2-mediated pentraxin 3 production in human nasal fibroblast cells
[ J Cell Physiol, 2021, 10.1002/jcp.30657]
Cross-talk between LAM cells and fibroblasts may influence alveolar epithelial cell behavior in Lymphangioleiomyomatosis
[ Am J Physiol Lung Cell Mol Physiol, 2021, 10.1152/ajplung.00351.2021]
Diverse Resistance Mechanisms to the Third-Generation ALK Inhibitor Lorlatinib in ALK-Rearranged Lung Cancer.
[ Clin Cancer Res, 2019, 10.1158/1078-0432.CCR-19-1104]
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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.
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