WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206156
CAS#: 1265229-25-1
Description: Debio-1347, also known as FF284 and CH5183284, is an orally bioavailable inhibitor of the fibroblast growth factor receptor subtypes 1 (FGFR-1), 2 (FGFR-2) and 3 (FGFR-3), with potential antineoplastic activity. 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.
MedKoo Cat#: 206156
Name: Debio-1347
CAS#: 1265229-25-1
Chemical Formula: C20H16N6O
Exact Mass: 356.13856
Molecular Weight: 356.38
Elemental Analysis: C, 67.40; H, 4.53; N, 23.58; O, 4.49
Related CAS #: 1265229-25-1 1265231-80-8
Synonym: Debio-1347; Debio 1347; Debio1347; CH5183284; CH 5183284; CH-5183284; FF284; FF-284; FF 284.
IUPAC/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
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | CH5183284 (Debio 1347) is a FGFR inhibitor with IC50s of 9.3, 7.6, and 22 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively. |
| In vitro activity: | Following this rationale, this study predicted that a selectivity of CH5183284/Debio 1347 for FGFR1, FGFR2, and FGFR3 would manifest as a selective activity to cell lines with activating alterations in these FGFRs. To test this, the antiproliferative activity of CH5183284/Debio 1347 was assessed against a large panel of 327 human tumor cell lines that were genetically profiled (Fig. 3; Supplementary Table S3). CH5183284/Debio 1347–sensitive cancer cell lines harboring genetic alterations in FGFR accounted for 20 of 24 (83%) of the lines examined. Together, these data indicate that the FGFR-selective inhibitor CH5183284/Debio 1347 has selective antiproliferative activity against cancer cell lines harboring genetic alterations in FGFR. Reference: Mol Cancer Ther. 2014 Nov;13(11):2547-58. https://mct.aacrjournals.org/content/13/11/2547.long |
| In vivo activity: | Compound 8 (Debio 1347) was orally administered once daily for 11 days, and the body weight of mice and the volume of the tumors were measured twice a week. A dose-dependent tumor regression (tumor growth inhibition (TGI) = 106% at 30 mg/kg and 147% at 100 mg/kg) was observed without apparent body weight loss. Compound 8 also showed significant in vivo efficacy in xenograft mice models with FGFR genetic alterations, such as 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). These results suggested 8’s therapeutic potential of cancers harboring FGFR genetic alterations. Reference: J Med Chem. 2016 Dec 8;59(23):10586-10600. https://pubmed.ncbi.nlm.nih.gov/27933954/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 32.33 | 90.72 | |
| DMSO:PBS (pH 7.2) (1:6) | 0.1 | 0.28 | |
| DMF | 1.0 | 2.81 | |
| Ethanol | 2.0 | 5.61 |
The following data is based on the product molecular weight 356.38 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Ebiike H, Taka N, Matsushita M, Ohmori M, Takami K, Hyohdoh I, Kohchi M, Hayase T, Nishii H, Morikami K, Nakanishi Y, Akiyama N, Shindoh H, Ishii N, Isobe T, Matsuoka H. Discovery of [5-Amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-(1H-indol-2-yl)methanone (CH5183284/Debio 1347), An Orally Available and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. J Med Chem. 2016 Dec 8;59(23):10586-10600. doi: 10.1021/acs.jmedchem.6b01156. Epub 2016 Nov 29. PMID: 27933954. 2. Nakanishi Y, Akiyama N, Tsukaguchi T, Fujii T, Sakata K, Sase H, Isobe T, Morikami K, Shindoh H, Mio T, Ebiike H, Taka N, Aoki Y, Ishii N. 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. doi: 10.1158/1535-7163.MCT-14-0248. Epub 2014 Aug 28. PMID: 25169980. |
| In vitro protocol: | 1. Ebiike H, Taka N, Matsushita M, Ohmori M, Takami K, Hyohdoh I, Kohchi M, Hayase T, Nishii H, Morikami K, Nakanishi Y, Akiyama N, Shindoh H, Ishii N, Isobe T, Matsuoka H. Discovery of [5-Amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-(1H-indol-2-yl)methanone (CH5183284/Debio 1347), An Orally Available and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. J Med Chem. 2016 Dec 8;59(23):10586-10600. doi: 10.1021/acs.jmedchem.6b01156. Epub 2016 Nov 29. PMID: 27933954. 2. Nakanishi Y, Akiyama N, Tsukaguchi T, Fujii T, Sakata K, Sase H, Isobe T, Morikami K, Shindoh H, Mio T, Ebiike H, Taka N, Aoki Y, Ishii N. 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. doi: 10.1158/1535-7163.MCT-14-0248. Epub 2014 Aug 28. PMID: 25169980. |
| In vivo protocol: | 1. Ebiike H, Taka N, Matsushita M, Ohmori M, Takami K, Hyohdoh I, Kohchi M, Hayase T, Nishii H, Morikami K, Nakanishi Y, Akiyama N, Shindoh H, Ishii N, Isobe T, Matsuoka H. Discovery of [5-Amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-(1H-indol-2-yl)methanone (CH5183284/Debio 1347), An Orally Available and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. J Med Chem. 2016 Dec 8;59(23):10586-10600. doi: 10.1021/acs.jmedchem.6b01156. Epub 2016 Nov 29. PMID: 27933954. 2. Nakanishi Y, Akiyama N, Tsukaguchi T, Fujii T, Sakata K, Sase H, Isobe T, Morikami K, Shindoh H, Mio T, Ebiike H, Taka N, Aoki Y, Ishii N. 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. doi: 10.1158/1535-7163.MCT-14-0248. Epub 2014 Aug 28. PMID: 25169980. |
