1448169-71-8 Usage
Description
FGFR-IN-1, also known as Futibatinib, is an orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) with potential antineoplastic activity. It selectively and irreversibly binds to and inhibits FGFR, which may result in the inhibition of both the FGFR-mediated signal transduction pathway and tumor cell proliferation, and increased cell death in FGFR-overexpressing tumor cells. FGFR is a receptor tyrosine kinase essential to tumor cell proliferation, differentiation, and survival, and its expression is upregulated in many tumor cell types.
Uses
Used in Anticancer Applications:
FGFR-IN-1 is used as an antineoplastic agent for inhibiting the fibroblast growth factor receptor (FGFR) in tumor cells. This inhibition may result in the suppression of the FGFR-mediated signal transduction pathway, leading to the prevention of tumor cell proliferation and promotion of cell death in FGFR-overexpressing tumor cells.
Used in Drug Development:
FGFR-IN-1 is used as a pharmaceutical candidate for the development of targeted therapies against various types of cancer. Its selective and irreversible binding to FGFR makes it a promising option for the treatment of cancers with upregulated FGFR expression, potentially improving patient outcomes and survival rates.
Used in Research and Development:
FGFR-IN-1 is used as a research tool for studying the role of FGFR in tumor cell proliferation, differentiation, and survival. It can be employed in preclinical studies to investigate the potential therapeutic effects of FGFR inhibition in various cancer models, as well as to identify potential synergistic effects with other antineoplastic agents.
Used in Drug Delivery Systems:
FGFR-IN-1 is used as an active pharmaceutical ingredient in the development of novel drug delivery systems, aiming to enhance its delivery, bioavailability, and therapeutic outcomes. Various organic and metallic nanoparticles can be employed as carriers for FGFR-IN-1 delivery, potentially improving its efficacy against cancer cells and reducing systemic side effects.
Synthesis
The synthesis of?Futibatinib is as follows:2 methanesulfonate (25.0 g), water (69 mL), and acetonitrile (158 mL) were placed in a reaction vessel, and a 5N aqueous sodium hydroxide solution (35 mL) was added thereto. A solution prepared by diluting 3-chloropropionyl chloride (6.27 g) with acetonitrile (50 mL) was added over a period of 10 minutes. After completion of the dropwise addition, the mixture was stirred at 30° C. for 30 minutes. The reaction solution was partially taken out and measured by HPLC (condition 3). The peak area of compound B was confirmed to be less than 0.1% of the total peak area. At this stage, the diamide compound and the 3CP diamide compound were not detected in HPLC. Thereafter, a 5N aqueous sodium hydroxide solution (25 mL) was further added, and the mixture was stirred at 30° C. for 4 hours. The reaction solution was partially taken out and measured by HPLC (condition 3). The peak area of the A-1-3CP compound was confirmed to be less than 0.1% of the total peak area. After completion of the reaction, water (550 mL) was added over a period of 2 hours. After completion of the dropwise addition, the internal temperature was adjusted to 25° C., and the mixture was stirred for 1.5 hours. The insoluble matter was collected by filtration and washed with water (125 mL), followed by drying the washed matter at 60° C. under reduced pressure, thereby obtaining the Futibatinib (16.02 g, yield 85.3%).
in vitro
Futibatinib (TAS-120) covalently binds to a highly conserved P-loop cysteine residue in the ATP pocket of FGFR.
in vivo
Futibatinib (TAS-120) (3, 30, 100 mg/kg/day, p.o.) exerts an anti-tumor
effect in mice. Futibatinib (TAS-120) shows anti-tumor effect by
administering at moderate intervals, such as intermittent administration
of every other day dosing and 2 times/week, and reducing the sustained
elevation and weight suppression blood phosphorus level, and take a
antitumor effective as daily administration.
Check Digit Verification of cas no
The CAS Registry Mumber 1448169-71-8 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,4,8,1,6 and 9 respectively; the second part has 2 digits, 7 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 1448169-71:
(9*1)+(8*4)+(7*4)+(6*8)+(5*1)+(4*6)+(3*9)+(2*7)+(1*1)=188
188 % 10 = 8
So 1448169-71-8 is a valid CAS Registry Number.
1448169-71-8Relevant articles and documents
METHOD FOR PRODUCING DIMETHOXYBENZENE COMPOUND
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, (2021/12/29)
A method for producing a compound represented by formula (A-1) or a salt thereof, the method comprising reacting (S)-3-((3,5-dimethoxyphenyl)ethynyl)-1-(pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine or a salt thereof with a compound represented by formula (I-1-A). Formula (I-1-A) and formula (A-1) are as described in the specification.
ANTITUMOR DRUG FOR INTERMITTENT ADMINISTRATION OF FGFR INHIBITOR
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Paragraph 0288, (2016/08/07)
The problem to be solved by the present invention is to provide a potent and highly selective novel FGFR inhibitor, and an antitumor agent having reduced side effects, such as increased blood phosphorus levels, while maintaining the antitumor effect of the FGFR inhibitor. The present invention provides an antitumor agent comprising a 3,5-disubstituted benzene alkynyl compound represented by Formula (I) or a salt thereof that is used so that the 3,5-disubstituted benzene alkynyl compound or a salt thereof is administered on an administration schedule of at least twice a week and a dosing interval of at least one day.
