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MedKoo Cat#: 206533 | Name: Roblitinib
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

Roblitinib
Roblitinib
CAS#1708971-55-4 (free base)

Theoretical Analysis

MedKoo Cat#: 206533

Name: Roblitinib

CAS#: 1708971-55-4 (free base)

Chemical Formula: C25H30N8O4

Exact Mass: 506.2390

Molecular Weight: 506.57

Elemental Analysis: C, 59.28; H, 5.97; N, 22.12; O, 12.63

Price and Availability

Size Price Availability Quantity
5mg USD 150.00 Ready to ship
10mg USD 250.00 Ready to ship
25mg USD 450.00 Ready to ship
50mg USD 750.00 Ready to ship
100mg USD 1,250.00 Ready to ship
200mg USD 2,050.00 Ready to Ship
1g USD 3,650.00 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/
Solvent mg/mL mM
Solubility
DMSO 5.4 10.66
Chloroform 30.0 59.22
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.
1: Yang Y, Zhang Y, Cao J, Su Z, Li F, Zhang P, Zhang B, Liu R, Zhang L, Xie J, Li J, Zhang J, Chen X, Hong A. FGFR4 and EZH2 inhibitors synergistically induce hepatocellular carcinoma apoptosis via repressing YAP signaling. J Exp Clin Cancer Res. 2023 Apr 22;42(1):96. doi: 10.1186/s13046-023-02659-4. PMID: 37085881; PMCID: PMC10122280. 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. 3: Wilbaux M, Demanse D, Gu Y, Jullion A, Myers A, Katsanou V, Meille C. Contribution of machine learning to tumor growth inhibition modeling for hepatocellular carcinoma patients under Roblitinib (FGF401) drug treatment. CPT Pharmacometrics Syst Pharmacol. 2022 Aug;11(8):1122-1134. doi: 10.1002/psp4.12831. Epub 2022 Jun 21. PMID: 35728123; PMCID: PMC9381917. 4: Wilbaux M, Yang S, Jullion A, Demanse D, Porta DG, Myers A, Meille C, Gu Y. Integration of Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy into Model-Informed Dose Selection in Oncology First-in-Human Study: A Case of Roblitinib (FGF401). Clin Pharmacol Ther. 2022 Dec;112(6):1329-1339. doi: 10.1002/cpt.2752. Epub 2022 Oct 18. PMID: 36131557. 5: Zhang S, Guo L, Tao R, Liu S. Ferroptosis-targeting drugs in breast cancer. J Drug Target. 2024 Sep 5:1-18. doi: 10.1080/1061186X.2024.2399181. Epub ahead of print. PMID: 39225187. 6: Di Giorgio C, Bellini R, Lupia A, Massa C, Urbani G, Bordoni M, Marchianò S, Rosselli R, De Gregorio R, Rapacciuolo P, Sepe V, Morretta E, Monti MC, Moraca F, Cari L, Ullah KRS, Natalizi N, Graziosi L, Distrutti E, Biagioli M, Catalanotti B, Donini A, Zampella A, Fiorucci S. The leukemia inhibitory factor regulates fibroblast growth factor receptor 4 transcription in gastric cancer. Cell Oncol (Dordr). 2024 Apr;47(2):695-710. doi: 10.1007/s13402-023-00893-8. Epub 2023 Nov 9. PMID: 37945798; PMCID: PMC11090936. 7: 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. 8: Chan SL, Schuler M, Kang YK, Yen CJ, Edeline J, Choo SP, Lin CC, Okusaka T, Weiss KH, Macarulla T, Cattan S, Blanc JF, Lee KH, Maur M, Pant S, Kudo M, Assenat E, Zhu AX, Yau T, Lim HY, Bruix J, Geier A, Guillén-Ponce C, Fasolo A, Finn RS, Fan J, Vogel A, Qin S, Riester M, Katsanou V, Chaudhari M, Kakizume T, Gu Y, Porta DG, Myers A, Delord JP. A first-in-human phase 1/2 study of FGF401 and combination of FGF401 with spartalizumab in patients with hepatocellular carcinoma or biomarker-selected solid tumors. J Exp Clin Cancer Res. 2022 Jun 2;41(1):189. doi: 10.1186/s13046-022-02383-5. PMID: 35655320; PMCID: PMC9161616. 9: Schadt HS, Wolf A, Mahl JA, Wuersch K, Couttet P, Schwald M, Fischer A, Lienard M, Emotte C, Teng CH, Skuba E, Richardson TA, Manenti L, Weiss A, Graus Porta D, Fairhurst RA, Kullak-Ublick GA, Chibout SD, Pognan F, Kluwe W, Kinyamu- Akunda J. Bile Acid Sequestration by Cholestyramine Mitigates FGFR4 Inhibition- Induced ALT Elevation. Toxicol Sci. 2018 May 1;163(1):265-278. doi: 10.1093/toxsci/kfy031. PMID: 29432567. 10: 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. 11: Zhou Z , Chen X , Fu Y , Zhang Y , Dai S , Li J , Chen L , Xu G , Chen Z , Chen Y . Characterization of FGF401 as a reversible covalent inhibitor of fibroblast growth factor receptor 4. Chem Commun (Camb). 2019 May 21;55(42):5890-5893. doi: 10.1039/c9cc02052g. PMID: 31041948.