| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
FGFR
Fibroblast growth factor receptors (FGFRs) - pan-FGFR inhibitor (ATP-competitive). Infigratinib is an ATP-competitive pan-FGFR inhibitor targeting FGFR1, FGFR2, FGFR3, and FGFR4. FGFRs are receptor tyrosine kinases that play critical roles in cell proliferation, survival, migration, and differentiation. Dysregulation of FGFR signaling through gene amplifications, mutations, or fusions is implicated in various cancers, including cholangiocarcinoma, bladder cancer, breast cancer, and lung cancer. Infigratinib binds to the ATP-binding pocket of FGFRs, competitively inhibiting ATP binding and thereby blocking receptor autophosphorylation and downstream signaling pathways, including RAS-MAPK and PI3K-AKT. Infigratinib-Boc itself is a protected intermediate that does not directly bind to FGFRs; the Boc group is removed during synthesis to generate the active Infigratinib molecule. |
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| ln Vitro |
Infigratinib-Boc is the BOC-protected Infigratinib which is an ATP-competitive pan-FGFR inhibitor. Infigratinib-Boc can be used for the synthesis of DGY-09-192, which is s PROTAC degrader of FGFR.
As a Boc-protected derivative of Infigratinib, Infigratinib-Boc retains the FGFR inhibitory pharmacophore but requires deprotection to yield the active compound. Infigratinib is a potent ATP-competitive pan-FGFR inhibitor with activity against FGFR1, FGFR2, FGFR3, and FGFR4. In preclinical studies, Infigratinib has demonstrated potent antiproliferative activity against cancer cell lines harboring FGFR alterations, including FGFR2 fusions and FGFR amplifications. The parent compound has been shown to inhibit FGFR phosphorylation and downstream signaling, leading to cell cycle arrest and apoptosis in FGFR-dependent cancer cells. Infigratinib-Boc serves as a synthetic intermediate for the preparation of FGFR-targeted PROTAC degraders (e.g., DGY-09-192), which offer a novel mechanism of action by inducing targeted degradation of FGFR proteins rather than simple inhibition. |
| ln Vivo |
Infigratinib-Boc is not intended for direct in vivo pharmacological studies; it is a chemical intermediate used in the synthesis of active therapeutic agents. The parent compound Infigratinib has demonstrated clinical efficacy in FGFR-driven cancers such as cholangiocarcinoma and is FDA-approved for this indication. In preclinical models, Infigratinib has shown potent antitumor activity in xenograft models bearing FGFR2-driven tumors. The PROTAC degrader DGY-09-192, synthesized using Infigratinib-Boc as a precursor, has been developed as a next-generation therapeutic agent with the potential to overcome resistance mechanisms associated with conventional FGFR inhibitors.
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| Enzyme Assay |
In vitro kinase assays are performed using recombinant FGFR enzymes (FGFR1, FGFR2, FGFR3, FGFR4) incubated with ATP substrate and varying concentrations of Infigratinib (parent compound). Phosphorylation of peptide substrates is measured via radiometric (e.g., 33P-ATP incorporation), fluorescence-based, or ELISA-based methods to determine IC50 values for ATP-competitive inhibition. The assays are typically carried out in optimized buffer conditions (e.g., HEPES pH 7.5, MgCl2, DTT) at room temperature or 30°C. The concentration of ATP is usually set at the Km for each FGFR isoform to accurately assess competitive inhibition. Dose-response curves are fitted to determine IC50 values.
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| Cell Assay |
Cancer cell lines with FGFR aberrations (e.g., cholangiocarcinoma, bladder cancer, breast cancer) are treated with Infigratinib (parent compound) at graded concentrations for 72-96 hours. Cell viability is assessed using standard assays (MTT, CCK-8, CellTiter-Glo) to determine antiproliferative IC50 values. FGFR phosphorylation and downstream signaling (e.g., p-ERK, p-AKT) are measured by Western blotting to confirm target engagement. For PROTAC degraders synthesized from Infigratinib-Boc, additional assays include measurement of FGFR protein degradation by Western blotting and assessment of antiproliferative activity.
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| Animal Protocol |
Mouse xenograft models bearing FGFR-driven tumors (e.g., cholangiocarcinoma xenografts with FGFR2 fusions) are administered Infigratinib (parent compound) orally at various doses. Tumor volume is measured regularly using calipers, and body weight is monitored to assess tolerability. Treatment is typically continued for 2-4 weeks. Tumor tissue is collected for pharmacodynamic analysis (e.g., FGFR phosphorylation inhibition, downstream signaling, and for PROTAC degraders, FGFR protein degradation). Efficacy is assessed by tumor growth inhibition, and toxicity is evaluated by body weight changes and histopathological examination of major organs.
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| ADME/Pharmacokinetics |
As a Boc-protected intermediate, Infigratinib-Boc is designed for synthetic utility rather than direct therapeutic use. The parent drug Infigratinib shows favorable oral bioavailability and is clinically approved. Infigratinib is absorbed after oral administration and reaches therapeutic concentrations in plasma. The Boc group in Infigratinib-Boc is typically removed under acidic conditions (e.g., TFA in DCM) during the final stages of synthesis to yield the active API. Pharmacokinetic properties of the final active compound are well-characterized from clinical studies, including Cmax, Tmax, AUC, t1/2, and plasma protein binding.
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| Toxicity/Toxicokinetics |
Infigratinib-Boc is a chemical intermediate and is not intended for direct in vivo use. The parent compound Infigratinib has been evaluated in clinical trials with manageable toxicity profiles. Common adverse effects include hyperphosphatemia (due to FGFR inhibition affecting phosphate homeostasis), gastrointestinal effects (diarrhea, nausea, vomiting), fatigue, and ocular toxicities (dry eye, corneal toxicity). More serious adverse events may include nail toxicity, stomatitis, and hand-foot syndrome. As a chemical intermediate, Infigratinib-Boc is handled with standard laboratory safety practices and is not for human consumption.
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| References | |
| Additional Infomation |
Aberrant activation of the FGFR signaling pathway occurs in various cancers, and ATP-competitive FGFR inhibitors have been approved by regulatory agencies. Although these inhibitors have demonstrated clinical efficacy, their lack of selectivity for FGFR family members leads to dose-limiting toxicity and poor tolerability. This article reports the discovery and characterization of DGY-09-192, a bivalent degrader that conjugates the pan-FGFR inhibitor BGJ398 to a CRL2VHL E3 ligase recruitment ligand, preferentially inducing the degradation of FGFR1 and 2, while having less effect on FGFR3 and 4. DGY-09-192 exhibits double-digit nanomolar DC50 values against wild-type FGFR2 and various FGFR2 fusion proteins, thus demonstrating degradation-dependent antiproliferative activity in representative gastric and cholangiocarcinoma cells. Importantly, DGY-09-192 induced the degradation of clinically significant FGFR2 fusion proteins in a xenograft model. In conclusion, we demonstrate that DGY-09-192 has the potential to serve as a prototype FGFR degrader. [1]
Infigratinib-Boc is a research-grade chemical intermediate used in PROTAC and drug discovery. Molecular formula: C29H35Cl2N7O5, molecular weight: 632.54 g/mol. Soluble in DMSO (100 mg/mL). Stored as powder at -20°C. It is used to synthesize PROTAC degraders targeting FGFR, such as DGY-09-192. The Boc protecting group on the piperazine nitrogen is a key structural feature enabling specific synthetic pathways. Synonyms: Infigratinib-Boc is the Boc-protected form of Infigratinib. It is an essential precursor for the development of next-generation FGFR-targeted therapies. For research use only, not for human therapeutic use. |
| Exact Mass |
631.20767
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| CAS # |
2504949-83-9
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| PubChem CID |
164788080
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
43
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| Complexity |
898
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C)OC(=O)N1CCN(CC1)C2=CC=C(C=C2)NC3=CC(=NC=N3)N(C)C(=O)NC4=C(C(=CC(=C4Cl)OC)OC)Cl
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| InChi Key |
BOVHQINAYHONJL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H35Cl2N7O5/c1-29(2,3)43-28(40)38-13-11-37(12-14-38)19-9-7-18(8-10-19)34-22-16-23(33-17-32-22)36(4)27(39)35-26-24(30)20(41-5)15-21(42-6)25(26)31/h7-10,15-17H,11-14H2,1-6H3,(H,35,39)(H,32,33,34)
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| Chemical Name |
tert-butyl 4-[4-[[6-[(2,6-dichloro-3,5-dimethoxyphenyl)carbamoyl-methylamino]pyrimidin-4-yl]amino]phenyl]piperazine-1-carboxylate
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| Synonyms |
Infigratinib-Boc; 2504949-83-9; SCHEMBL24490250;
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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 |
| 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) |
Typically soluble in DMSO (e.g. 10 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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.
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