WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H206533
CAS#: 1708971-55-4 (free base)
Description: Roblitinib, also known as FGF401, is an inhibitor of human fibroblast growth factor receptor 4 (FGFR4) with potential antineoplastic activity. Upon administration, FGF401 binds to and inhibits the activity of FGFR4, which leads to an inhibition of tumor cell proliferation in FGFR4-overexpressing cells. FGFR4 is a receptor tyrosine kinase upregulated in certain tumor cells and involved in tumor cell proliferation, differentiation, angiogenesis, and survival.
Hodoodo Cat#: H206533
Name: Roblitinib
CAS#: 1708971-55-4 (free base)
Chemical Formula: C25H30N8O4
Exact Mass: 506.24
Molecular Weight: 506.567
Elemental Analysis: C, 59.28; H, 5.97; N, 22.12; O, 12.63
Related CAS #: 1708971-60-1 (citrate) 1708971-55-4 (free base)
Synonym: FGF401; FGF-401; FGF 401; roblitinib;
IUPAC/Chemical Name: N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide
InChi Key: BHKDKKZMPODMIQ-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H30N8O4/c1-31-7-8-32(23(35)15-31)14-18-10-17-4-3-6-33(24(17)29-21(18)16-34)25(36)30-22-11-20(27-5-9-37-2)19(12-26)13-28-22/h10-11,13,16H,3-9,14-15H2,1-2H3,(H2,27,28,30,36)
SMILES Code: CN1CC(N(CC2=CC(CCCN3C(NC4=CC(NCCOC)=C(C#N)C=N4)=O)=C3N=C2C=O)CC1)=O
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
More Info:
Biological target: | Roblitinib (FGF-401) is a FGFR4 inhibitor with an IC50 of 1.9 nM. |
In vitro activity: | FGF401 increased the percentage of cells in the G1 and sub-G1 phases with a concomitant decrease in the percentage of cells in the G2/M and S phases, suggesting that FGF401 causes G1 cell cycle arrest (Fig. 1c). The phosphorylation of FRS-2α was assessed at Tyr436 and p-Erk1/2 as a measure of FGF19/FGFR-4 signaling activity. FGF19 stimulated the phosphorylation of FRS-2α and the downstream signaling molecule Erk1/2; however, this was abolished when cells were pretreated with FGF401 for 24 h, suggesting the ability of FGF401 to inhibit the FRS-2α/Erk1/2 pathway (Fig. 1d). Reference: Exp Mol Med. 2020 Nov;52(11):1857-1868. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080677/ |
In vivo activity: | Treatment of mice bearing high FGF19-expressing HCC25-0705A tumors with 20, 30, and 40 mg/kg FGF401 twice a day led to 83.5%, 86.8, and 87% reductions in tumor burden, respectively (p |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
DMSO | 5.4 | 10.66 | |
Chloroform | 30.0 | 59.22 |
The following data is based on the product molecular weight 506.57 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. Huynh H, Prawira A, Le TBU, Vu TC, Hao HX, Huang A, Wang Y, Porta DG. FGF401 and vinorelbine synergistically mediate antitumor activity and vascular normalization in FGF19-dependent hepatocellular carcinoma. Exp Mol Med. 2020 Nov;52(11):1857-1868. doi: 10.1038/s12276-020-00524-4. Epub 2020 Nov 25. PMID: 33235319; PMCID: PMC8080677. |
In vitro protocol: | 1. Huynh H, Prawira A, Le TBU, Vu TC, Hao HX, Huang A, Wang Y, Porta DG. FGF401 and vinorelbine synergistically mediate antitumor activity and vascular normalization in FGF19-dependent hepatocellular carcinoma. Exp Mol Med. 2020 Nov;52(11):1857-1868. doi: 10.1038/s12276-020-00524-4. Epub 2020 Nov 25. PMID: 33235319; PMCID: PMC8080677. |
In vivo protocol: | 1. Huynh H, Prawira A, Le TBU, Vu TC, Hao HX, Huang A, Wang Y, Porta DG. FGF401 and vinorelbine synergistically mediate antitumor activity and vascular normalization in FGF19-dependent hepatocellular carcinoma. Exp Mol Med. 2020 Nov;52(11):1857-1868. doi: 10.1038/s12276-020-00524-4. Epub 2020 Nov 25. PMID: 33235319; PMCID: PMC8080677. |
1. Roskoski R Jr. The role of fibroblast growth factor receptor (FGFR) protein-tyrosine kinase inhibitors in the treatment of cancers including those of the urinary bladder. Pharmacol Res. 2020 Jan;151:104567. doi: 10.1016/j.phrs.2019.104567. Epub 2019 Nov 23. PMID: 31770593.
2. Fairhurst RA, Knoepfel T, Buschmann N, Leblanc C, Mah R, Todorov M, Nimsgern P, Ripoche S, Niklaus M, Warin N, Luu VH, Madoerin M, Wirth J, Graus-Porta D, Weiss A, Kiffe M, Wartmann M, Kinyamu-Akunda J, Sterker D, Stamm C, Adler F, Buhles A, Schadt H, Couttet P, Blank J, Galuba I, Trappe J, Voshol J, Ostermann N, Zou C, Berghausen J, Del Rio Espinola A, Jahnke W, Furet P. Discovery of Roblitinib (FGF401) as a Reversible-Covalent Inhibitor of the Kinase Activity of Fibroblast Growth Factor Receptor 4. J Med Chem. 2020 Nov 12;63(21):12542-12573. doi: 10.1021/acs.jmedchem.0c01019. Epub 2020 Oct 1. PMID: 32930584.