Roblitinib
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MedKoo CAT#: 206533

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.

Chemical Structure

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Roblitinib
CAS# 1708971-55-4 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206533
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

Price and Availability

Size Price Availability Quantity
5mg USD 150 Ready to ship
10mg USD 250 Ready to ship
25mg USD 450 Ready to ship
50mg USD 750 Ready to ship
100mg USD 1250 Ready to ship
200mg USD 2050 Ready to Ship
1g USD 3650 2 Weeks
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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 < 0.0001, Fig. 1e). Moreover, FGF401 significantly reduced p-Histone H3 Ser10 and increased the proportion of cleaved PARP-positive cells in a dose-dependent manner (Fig. 1f). Moreover, the suppression of p-FRS-2α and p-Erk1/2 and the increase in cleaved caspase 3 occurred within 3–12 h after drug administration (Supplementary Fig. 2a). Reference: Exp Mol Med. 2020 Nov;52(11):1857-1868. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080677/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 5.4 10.66
Chloroform 30.0 59.22

Preparing Stock Solutions

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.

Recalculate based on batch purity %
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.

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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.