Share this post on:

product name CH5183284 (Debio-1347)


Description: CH5183284, also known as FF284 and Debio-1347, is a potent, 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. FGFR inhibitor debio 1347 binds to and inhibits FGFR-1, -2, and -3, which result in the inhibition of FGFR-mediated signal transduction pathways. This leads to the inhibition of both tumor cell proliferation and angiogenesis, and causes cell death in FGFR-overexpressing tumor cells. 

References: Mol Cancer Ther. 2014 Nov;13(11):2547-58.



Molecular Weight (MW)

356.38
Formula

C20H16N6O
CAS No.

1265229-25-1
Storage

-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)

DMSO: 71 mg/mL (199.2 mM)
Water: <1 mg/mL
Ethanol: 1 mg/mL (2.8 mM)
Solubility (In vivo)

 
Synonyms

FF284, CH5183284

other peoduct :References PubMed ID::http://www.ncbi.nlm.nih.gov/pubmed/19420631

In Vitro

In vitro activity: 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 harboring genetic alterations in FGFR. CH5183284 also inhibit FGFR2 harboring one type of the gatekeeper mutation (V564F) that causes resistance to other FGFR inhibitors.


Kinase Assay: 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 labeled 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 polarization is measured with an EnVision HTS microplate reader.


Cell Assay: The cell lines (327 human tumor 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.

In Vivo CH5183284 (100 mg/kg/day, p.o.) shows selective and significant antitumor activity against xenografts with FGFR genetic alterations such as KG1 (leukemia, 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).
Animal model Mice bearing KG1, SNU-16, MFE280, UM-UC-14, RT112/84, or MKN-45 tumors
Formulation & Dosage Formulated in 0.5% carmellose sodium, 0.5% polysorbate 20, and 0.9% benzyl alcohol in purified water; 100 mg/kg; oral gavage
References Mol Cancer Ther. 2014 Nov;13(11):2547-58.

Ebselen

Share this post on:

Author: Sodium channel