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Purity: ≥98%
Infigratinib phosphate (formerly BGJ-398; BGJ398; NVP-BGJ398 phosphate; Truseltiq), the phosphate salt of Infigratinib, is an orally bioavailable FGFR (fibroblast growth factor receptors) inhibitor that has gained FDA approval in May 2021 to treat cholangiocarcinoma whose disease meets certain criteria.In cell-free experiments, it inhibits FGFR1/2/3 with IC50s of 0.9 nM/1.4 nM/1 nM, suggesting that it may have antiangiogenic and antineoplastic properties.
| Targets |
FGFR1 (IC50 = 0.9 nM); FGFR2 (IC50 = 1.4 nM); FGFR3 (IC50 = 1 nM); FGFR4 (IC50 = 60 nM)
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| ln Vitro |
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| Enzyme Assay |
The purified GST-fusion FGFR3-K650E kinase domain phosphorylates a synthetic substrate in the presence of radiolabeled ATP to measure the enzymatic kinase activity. Enzyme activities are determined by combining 10 μL of the corresponding substrate mixture (peptidic substrate, ATP, and [γ33P]ATP) with 10 μL of a 3-fold concentrated Infigratinib solution or control. The assay buffer is mixed with 10 μL of a concentrated enzyme solution three times over to start the reactions. The following are the assay components' final concentrations: 0.5 μM ATP (γ-[33P]-ATP 0.1 μCi), 3 mM MnCl2, 3 mM MgCl2, 1 mM DTT, 250 μg/mL PEG 20000, 2 μg/mL poly(EY) 4:1, 1% DMSO, and 10 ng of GST-FGFR3-K650E were added. The assay is performed using the filter binding (FB) method in 96-well plates for 10 minutes at room temperature and 30 μL of final volume, which includes the components mentioned above. The following measurement is used to determine the amount of 33P incorporated into the polypeptidic substrates after 20 μL of 125 mM EDTA is added to stop the enzymatic reactions: Using a disconnected vacuum source, mount the Immobilon-PVDF membranes on a vacuum manifold and transfer 30 μL of the stopped reaction mixture onto them after they have been soaked in methanol for 5 minutes, rinsed with water, and soaked in 0.5% H3PO4 for 5 minutes. Following spotting, each well is rinsed with 200 μL of 0.5% H3PO4 and vacuumed. After extracting the free membranes, they are shaker-washed four times with 1% H3PO4 and once with ethanol. After desiccating the membranes, 10 μL of a scintillation fluid are added per well. In the end, the plates are sealed and counted using a microplate scintillation counter. By using linear regression analysis to determine the percentage inhibition of NVP-BGJ398[1], IC50 values are determined.
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| Cell Assay |
RPMI-1640 medium supplemented with 10% FBS, 4.5 g/L glucose, 1.5 g/L sodium bicarbonate, and Pen/Strep is used to cultivate mouse BaF3 cell lines. Twice a week, cells are passed through. A Luciferase bioluminescent assay is used to evaluate compound-mediated inhibition of BaF3 cell proliferation and viability. Using a μFill liquid dispenser, exponentially growing BaF3 or BaF3 Tel-TK cells are seeded at 50 μL/well into 384-well plates (4250 cells/well) in fresh medium. After being serially diluted in DMSO, infigratinib is arranged in a 384-well polypropylene plate. The plates were then incubated at 37°C (5% CO2) for 48 hours after 50 nL of the compound was transferred into them using the pintool transfer device. Next, add 25 μL of Bright-Glo, and use an Analyst-GT to measure the luminescence. A logistic fit of the percent cell viability as a function of the logarithm of inhibitor concentration is generated using specialized curve-fitting software. The concentration of a compound required to lower cell viability to 50% of a DMSO control is known as the IC50 value[1].
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| Animal Protocol |
Mice: HsdNpa female: Athymic Nude-nu mice are employed. Infigratinib is taken orally for 12 straight days at doses of 10 and 30 mg/kg/qd. It is prepared as a suspension in PEG300/D5W (2:1, v/v). ANOVA is used to analyze the tumor and body weight data, and Dunnett's test is used to compare the treatment group to the control group post hoc. For intragroup comparison, the post hoc Tukey test is employed. To perform statistical analysis, use GraphPad Prism 4.02. One calculates the T/C (%) value as a measure of efficacy.
Rats: Woman in the nude 6 to 9-week-old Rowett rats are utilized. The tumor-bearing rats (n=8) receive infigratinib intraperitoneally (gavage) once a day for 20 days at doses of 5, 10, and 15 mg/kg/qd (free base equivalents). The drug is prepared as a solution in acetic acid-acetate buffer pH 4.6/PEG300 (1:1, v/v). It uses five milliliters per kilogram. The formula for determining tumor volumes is length×width×height×π/6, which can be measured using calipers. Antitumor activity is represented as T/C (%), which is calculated as (mean change in tumor volume of treated animals / mean change in tumor volume of control animals)×100. One calculates regressions (%). |
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| References |
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| Molecular Formula |
C26H34CL2N7O7P
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| Molecular Weight |
658.47
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| Exact Mass |
657.1634388
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| Elemental Analysis |
C, 47.43; H, 5.20; Cl, 10.77; N, 14.89; O, 17.01; P, 4.70
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| CAS # |
1310746-10-1
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| Related CAS # |
Infigratinib;872511-34-7
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| Appearance |
White to off-white solid powder
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| SMILES |
CCN1CCN(CC1)C2=CC=C(C=C2)NC3=CC(=NC=N3)N(C)C(=O)NC4=C(C(=CC(=C4Cl)OC)OC)Cl.OP(=O)(O)O
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| InChi Key |
GUQNHCGYHLSITB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H31Cl2N7O3.H3O4P/c1-5-34-10-12-35(13-11-34)18-8-6-17(7-9-18)31-21-15-22(30-16-29-21)33(2)26(36)32-25-23(27)19(37-3)14-20(38-4)24(25)28;1-5(2,3)4/h6-9,14-16H,5,10-13H2,1-4H3,(H,32,36)(H,29,30,31);(H3,1,2,3,4)
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| Chemical Name |
3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-[6-[4-(4-ethylpiperazin-1-yl)anilino]pyrimidin-4-yl]-1-methylurea;phosphoric acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5187 mL | 7.5934 mL | 15.1867 mL | |
| 5 mM | 0.3037 mL | 1.5187 mL | 3.0373 mL | |
| 10 mM | 0.1519 mL | 0.7593 mL | 1.5187 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05514912 | Not yet recruiting | Drug: Cisplatin Drug: Infigratinib Phosphate |
Stage 0 Intrahepatic Cholangiocarcinoma AJCC v8 Resectable Intrahepatic Cholangiocarcinoma |
Emory University | November 1, 2023 | Phase 2 |
| NCT04197986 | Terminated | Drug: Infigratinib Drug: Placebo |
Upper Tract Urothelial Carcinomas Urothelial Bladder Cancer |
QED Therapeutics, Inc. | March 11, 2020 | Phase 3 |
Targeting Fgfr2-fusion containing tumors with the FGFR-inhibitor BGJ398 results in complete response.Cancer Discov.2018 Mar;8(3):354-369. |
Multiple, different genetic aberrations lead to common elevated MAPK and/or PI3K pathway activation in human breast cancer patients.Cancer Discov.2018 Mar;8(3):354-369. |
Targeting Dhx9-Raf1 and cMet with MEK- and MET-inhibitor, respectively, result in tumor regression or delayed progression.
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