CH5183284 (Debio-1347)

Catalog No.

B4985

selective and orally available FGFR inhibitor

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Grouped product items
Size	Price	Stock
10mM (in 1mL DMSO)	$121.00	In stock
5mg	$55.00	In stock
25mg	$220.00	In stock
100mg	$698.00	In stock

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Background
Chemical Properties
Protocol
Quality Control

Background

CH5183284 (Debio-1347) is a selective and novel inhibitor of FGFR with IC50 value of 9.3, 7.6, 22 and 290 nM for FGFR1, FGFR2, FGFR3 and FGFR4, respectively [1].

Fibroblast growth factor receptors (FGFRs) are tyrosine kinases and receptors for fibroblast growth factors and consist of FGFR1, FGFR2, FGFR3 and FGFR4. In cancer, FGFR is activated by point mutations, gene amplification or chromosomal translocations/rearrangements and is involved in angiogenesis, cell growth, cell migration, invasion and metastasis [1].

CH5183284 (Debio-1347) is a selective and novel FGFR inhibitor. In a competitive binding assay, CH5183284 (Debio-1347) binding with FGFR1, FGFR2, FGFR3, FGFR4 and KDR with Kd values of 20, 20, 25, 740 and 960 nM, respectively. In DMS114, SNU-16 and KMS11 cell lines, CH5183284 (Debio-1347) (100-300 nM) inhibited autophosphorylation of FGFR1, FGFR2 and FGFR3. In cancer cell lines with the FGFR genetic alterations, CH5183284 (Debio-1347) showed antiproliferative activity [1].

In xenograft mouse models, CH5183284 (Debio-1347) inhibited tumor growth against xenografts with FGFR genetic alterations such as KG1 (leukemia, FGFR1OP-FGFR1 fusion), MFE-280 (endometrial cancer, FGFR2 S252W mutation), SNU-16 (gastric cancer, FGFR2 amplification), RT112/84 (bladder cancer, FGFR3-TACC3 fusion) and UM-UC-14 (bladder cancer, FGFR3 S249C mutation) by 134%, 100%, 147%, 125% and 116%, respectively [1].

Reference:
[1]. Nakanishi Y, Akiyama N, Tsukaguchi T, et al. The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitor. Mol Cancer Ther, 2014, 13(11): 2547-2558.

Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	356.38
Cas No.	1265229-25-1
Formula	C₂₀H₁₆N₆O
Solubility	≥35.6 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O
SDF	Download SDF
Canonical SMILES	CC1=NC(C=C2)=C(N1)C=C2N3N=CC(C(C(N4)=CC5=C4C=CC=C5)=O)=C3N
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Kinase experiment [1]:
Protein kinase assay	The inhibitory activity of CH5183284/Debio 1347 against FGFR1 was 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 were determined by homogeneous time-resolved fluorescence assay with LANCE Eu-W1024 labeled anti-phosphotyrosine PT66 antibody according to standard methods. Time-resolved fluorescence was 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 were determined by IMAP FP Screening Express Progressive Binding System. Fluorescence polarization was measured with an EnVision HTS microplate reader.
Cell experiment [1]:
Cell lines	327 human tumor cell lines
Preparation method	The solubility of this compound in DMSO is > 17.8 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.
Reacting condition	0.076 ~ 10,000 nM; 4 days
Applications	In DMS114 (FGFR1 amplification), SNU-16 (FGFR2 amplification) and KMS11 [t(4;14) translocation and FGFR3 Y373C mutation] cells, CH5183284 inhibited autophosphorylation of FGFR1, FGFR2 and FGFR3 at the dose range of 100 ~ 300 nM. Thus, CH5183284 selectively inhibited proliferation of cancer cell lines with genetic alterations in FGFR. In addition, CH5183284 also inhibited FGFR2-harboring cancer cells with V564F mutation which are resistant to other FGFR inhibitors.
Animal experiment [1]:
Animal models	Mice bearing KG1, MFE280, SNU-16, RT112/84 or UM-UC-14 xenografts
Dosage form	100 mg/kg/day; p.o.
Applications	CH5183284 exhibited selective and significant antitumor activities against various xenografts with FGFR genetic alterations such as KG1 (leukemia, FGFR1OP-FGFR1 fusion), MFE-280 (endometrial cancer, FGFR2 S252W mutation), SNU-16 (gastric cancer, FGFR2 amplification), RT112/84 (bladder cancer, FGFR3-TACC3 fusion) and UM-UC-14 (bladder cancer, FGFR3 S249C mutation).
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Nakanishi Y, Akiyama N, Tsukaguchi T, et al. The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitor. Mol Cancer Ther, 2014, 13(11): 2547-2558.