CH5183284 (FF-284; Debio-1347)

Alias: FF284; CH5183284; Debio1347; CH 5183284; CH-5183284; Debio-1347; Debio 1347; FF-284; FF 284
Cat No.:V0618 Purity: ≥98%
CH5183284 (also known as FF284; Debio-1347) is a novel, potent, selective and orally bioavailable FGFR inhibitor with potential antitumor activity.
CH5183284 (FF-284; Debio-1347) Chemical Structure CAS No.: 1265229-25-1
Product category: FGFR
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
25mg
50mg
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Other Forms of CH5183284 (FF-284; Debio-1347):

  • Debio-1347 (S)-hydroxysuccinate
Official Supplier of:
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Top Publications Citing lnvivochem Products
InvivoChem's CH5183284 (FF-284; Debio-1347) has been cited by 1 publication
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

CH5183284 (also known as FF284; Debio-1347) is a novel, potent, selective and orally bioavailable FGFR inhibitor with potential antitumor activity. It inhibits the FGFR1/2/3/4 mutants with IC50 values of 9.3 nM, 7.6 nM, 22 nM, and 290 nM, in that order. Excellent in vivo antitumor efficaciousness is demonstrated in mice with tumors KG1, SNU-16, MFE280, UM-UC-14, RT112/84, or MKN-45.

Biological Activity I Assay Protocols (From Reference)
Targets
FGFR1 (IC50 = 9.3 nM); FGFR2 (IC50 = 7.6 nM); FGFR3 (IC50 = 22 nM); FGFR4 (IC50 = 290 nM)
ln Vitro
Zoligratinib is well-balanced in terms of stability in human liver microsomes and cellular antiproliferative activity against SNU-16. It is hypothesized that the distinction in how 8 interacts with M535 in FGFR1 and L889 in KDR accounts for the selectivity of 8's inhibition of FGFR over KDR[1]. For FGF-dependent proliferation, zoligratinib's IC50 is 29 nM, while for VEGF-dependent proliferation, it is 780 nM[2].
ln Vivo
Zoligratinib treatment shows a dose-dependent tumor regression (tumor growth inhibition (TGI)=106% at 30 mg/kg and 147% at 100 mg/kg) without apparent body weight loss. Significant in vivo efficacy of zoligratină treatment is also observed in xenograft mouse models with FGFR genetic alterations, including KG1 (leukemia, FGFR1OP-FGFR1 fusion), MFE280 (endometrial cancer, FGFR2 S252W mutation), UM-UC-14 (bladder cancer, FGFR3 S249C mutation), and RT112/84 (bladder cancer, FGFR3-TACC3 fusion)[1].
Enzyme Assay
A radiometric filter assay is used to measure the incorporation of 33Pi using a microplate scintillation counter in order to assess the inhibitory activity of CH5183284/Debio 1347 against FGFR1. Standard techniques are used in a homogeneous time-resolved fluorescence assay to measure 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. Using an EnVision HTS microplate reader, time-resolved fluorescence is quantified. IMAP FP Screening Express Progressive Binding System measures the activities of all the proteins on substrate peptides, including PKA, Akt1/PKBα, PKA, Cdk1/cyclin B, Cdk2/cyclin A, PKCα, PKCβ1, and PKCβ2. It uses an EnVision HTS microplate reader to measure fluorescence polarization.
Cell Assay
The 96-well plate wells containing 0.076−10,000 nM tested compounds (CH5183284) are filled with the cell lines, and the plate is then incubated at 37°C. The Cell Counting Kit-8 solution is added after 4 days of incubation, and absorbance at 450 nm is measured several hours later. The formula for calculating antiproliferative activity is 1-T/C) × 100 (%), where T and C stand for the absorbance at 450 nm of drug-treated cells (T) and untreated control cells (C)[1].
Animal Protocol
Rats: To evaluate the effects on blood pressure (BP), male Wistar rats weighing between 340 and 390 grams are implanted with a telemetry transmitter. Oral gavage of either the vehicle (0.5% carmellose sodium, 0.5% polysorbate 20, and 0.9% benzyl alcohol in purified water) or CH5183284/Debio 1347 (10 and 30 mg/kg) is performed once daily for four days in a row. Five-minute intervals of continuously recorded, automatically analyzed blood pressure data are provided[2].
Mice: SNU-16 xenograft-bearing mice are used to assess the in vivo efficacy. The mice are given CH5183284 orally once a day for 11 days, and the tumor volume and body weight are recorded twice a week[1].
References

[1]. 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 Nov;13(11):2547-58.

[2]. Mechanism of Oncogenic Signal Activation by the Novel Fusion Kinase FGFR3-BAIAP2L1. Mol Cancer Ther. 2015 Mar;14(3):704-12.

[3]. ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor. Mol Cancer Ther. 2015 Dec;14(12):2831-9.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C20H16N6O
Molecular Weight
356.38
Exact Mass
356.14
Elemental Analysis
C, 67.40; H, 4.53; N, 23.58; O, 4.49
CAS #
1265229-25-1
Appearance
Solid powder
SMILES
CC1=NC2=C(N1)C=C(C=C2)N3C(=C(C=N3)C(=O)C4=CC5=CC=CC=C5N4)N
InChi Key
BEMNJULZEQTDJY-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H16N6O/c1-11-23-16-7-6-13(9-17(16)24-11)26-20(21)14(10-22-26)19(27)18-8-12-4-2-3-5-15(12)25-18/h2-10,25H,21H2,1H3,(H,23,24)
Chemical Name
[5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-(1H-indol-2-yl)methanone
Synonyms
FF284; CH5183284; Debio1347; CH 5183284; CH-5183284; Debio-1347; Debio 1347; FF-284; FF 284
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~71 mg/mL (~199.2 mM)
Water: <1 mg/mL
Ethanol: ~1 mg/mL (~2.8 mM)
Solubility (In Vivo)

Chemical Name:(5-amino-1-(2-methyl-1H-benzo[d]imidazol-6-yl)-1H-pyrazol-4-yl)(1H-indol-2-yl)methanone

InChi Key:BEMNJULZEQTDJY-UHFFFAOYSA-N

InChi Code:InChI=1S/C20H16N6O/c1-11-23-16-7-6-13(9-17(16)24-11)26-20(21)14(10-22-26)19(27)18-8-12-4-2-3-5-15(12)25-18/h2-10,25H,21H2,1H3,(H,23,24)

SMILES Code:O=C(C1=C(N)N(C2=CC=C3C(NC(C)=N3)=C2)N=C1)C(N4)=CC5=C4C=CC=C5

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.8060 mL 14.0300 mL 28.0599 mL
5 mM 0.5612 mL 2.8060 mL 5.6120 mL
10 mM 0.2806 mL 1.4030 mL 2.8060 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03344536 Completed Drug: Fulvestrant
Drug: Debio 1347
Breast Cancer Memorial Sloan Kettering
Cancer Center
November 10, 2017 Phase 1
Phase 2
NCT01948297 Terminated Drug: Debio1347
(CH5183284)
Solid Tumours Debiopharm International SA August 2013 Phase 1
NCT03834220 Terminated Drug: Debio 1347 Solid Tumor Debiopharm International SA March 22, 2019 Phase 2
Biological Data
  • CH5183284 (Debio-1347)

    Selective inhibitory activity against FGFR1, FGFR2, and FGFR3. Mol Cancer Ther. 2014 Nov;13(11):2547-58.

  • CH5183284 (Debio-1347)

    Selective antiproliferative activity of CH5183284/Debio 1347 against cancer cell lines harboring genetic alterations in FGFR. Mol Cancer Ther. 2014 Nov;13(11):2547-58.

  • CH5183284 (Debio-1347)

    Selective antitumor activity of CH5183284/Debio 1347 in mouse models of cell lines harboring genetic alterations in FGFR. Mol Cancer Ther. 2014 Nov;13(11):2547-58.

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