Infigratinib free base
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MedKoo CAT#: 204640

CAS#: 872511-34-7 (free base)

Description: Infigratinib, also known as, BGJ398 or NVP-BGJ398, is a pan FGFR kinase inhibitor, and is an orally bioavailable pan inhibitor of human fibroblast growth factor receptors (FGFRs) with potential antiangiogenic and antineoplastic activities. pan FGFR kinase inhibitor BGJ398 selectively binds to and inhibits the activities of FGFRs, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation, and the induction of tumor cell death. Infigratinib was approved in 2021 to treat adults with cholangiocarcinoma whose disease meets certain criteria.


Chemical Structure

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Infigratinib free base
CAS# 872511-34-7 (free base)

Theoretical Analysis

MedKoo Cat#: 204640
Name: Infigratinib free base
CAS#: 872511-34-7 (free base)
Chemical Formula: C26H31Cl2N7O3
Exact Mass: 559.18654
Molecular Weight: 560.47
Elemental Analysis: C, 55.72; H, 5.57; Cl, 12.65; N, 17.49; O, 8.56

Price and Availability

Size Price Availability Quantity
50.0mg USD 120.0 Ready to ship
100.0mg USD 190.0 Ready to ship
200.0mg USD 350.0 Ready to ship
500.0mg USD 750.0 Ready to ship
1.0g USD 1250.0 Ready to ship
2.0g USD 2250.0 Ready to ship
5.0g USD 3750.0 2 weeks
10.0g USD 5650.0 2 weeks
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Related CAS #: 872511-34-7 (free base)   1310746-10-1 (phosphate)   1310746-11-2 (monohydrate)   1310746-12-3 (mesylate)    

Synonym: NVPBGJ398; NVPBGJ 398; NVPBGJ-398; BGJ398; BGJ-398; BG J398; Infigratinib.

IUPAC/Chemical Name: 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-(6-((4-(4-ethylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)-1-methylurea.

InChi Key: QADPYRIHXKWUSV-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H31Cl2N7O3/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/h6-9,14-16H,5,10-13H2,1-4H3,(H,32,36)(H,29,30,31)

SMILES Code: O=C(NC1=C(Cl)C(OC)=CC(OC)=C1Cl)N(C2=NC=NC(NC3=CC=C(N4CCN(CC)CC4)C=C3)=C2)C

Appearance: White to off-white 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

Biological target: Infigratinib (BGJ-398; NVP-BGJ398) is an inhibitor of the FGFR family with IC50s of 0.9 nM, 1.4 nM, 1 nM, and 60 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively.
In vitro activity: Infigratinib inhibits FGF-induced activation of the FGFR signaling pathway and cell cycle progression. Pretreatment of HCC01-0909 cells with 1.0 µM Infigratinib for 18 hours abolished FGF-2-, FGF-1-, and FGF-19- stimulated phosphorylation of Fibroblast Growth Factor Receptor Substrate 2 alpha (FRS2-α) and extracellular signal-regulated kinase (ERK)1/2 (Fig. 1C). Infigratinib had no effect on HGF-induced phosphorylation of ERK1/2, suggesting that the inhibitory effect of infigratinib was specific to the FGF/FGFR signaling pathway. Infigratinib caused a significant increase in the percentage of cells in the G1 and sub-G1 phases with a concomitant reduction in the percentage of cells in the G2/M and S phases (Fig. 1D), suggesting that infigratinib causes G1 cell cycle arrest. Reference: Hepatology. 2019 Mar;69(3):943-958. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635738/
In vivo activity: Daily treatment of HCC06-0606 tumor-bearing mice with 10, 20, and 30 mg/kg infigratinib for 14 days led to approximately 65%, 96%, and 98% reductions in tumor burden, respectively (Fig. 1E). Daily treatment of mice with infigratinib resulted in significant elevation in alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) and a significant decrease in serum creatinine (Supporting Fig. S2). Infigratinib potently inhibited p-FRS2-α and p-ERK1/2 (Figure 1F), and the inhibition of these biomarkers occurred within 2 hours after a single oral dose of 20 mg/kg infigratinib, was maintained for approximately 10 hours, and returned to baseline by 12 hours after treatment (Fig. 2A). Reference: Hepatology. 2019 Mar;69(3):943-958. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635738/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 6.67 11.9
Water 0.05 0.09
DMF 5.0 8.92
DMF:PBS (pH 7.2) (1:30) 0.03 0.05

Preparing Stock Solutions

The following data is based on the product molecular weight 560.47 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, Lee LY, Goh KY, Ong R, Hao HX, Huang A, Wang Y, Graus Porta D, Chow P, Chung A. Infigratinib Mediates Vascular Normalization, Impairs Metastasis, and Improves Chemotherapy in Hepatocellular Carcinoma. Hepatology. 2019 Mar;69(3):943-958. doi: 10.1002/hep.30481. PMID: 30575985; PMCID: PMC6635738.
In vitro protocol: 1. Huynh H, Lee LY, Goh KY, Ong R, Hao HX, Huang A, Wang Y, Graus Porta D, Chow P, Chung A. Infigratinib Mediates Vascular Normalization, Impairs Metastasis, and Improves Chemotherapy in Hepatocellular Carcinoma. Hepatology. 2019 Mar;69(3):943-958. doi: 10.1002/hep.30481. PMID: 30575985; PMCID: PMC6635738.
In vivo protocol: 1. Huynh H, Lee LY, Goh KY, Ong R, Hao HX, Huang A, Wang Y, Graus Porta D, Chow P, Chung A. Infigratinib Mediates Vascular Normalization, Impairs Metastasis, and Improves Chemotherapy in Hepatocellular Carcinoma. Hepatology. 2019 Mar;69(3):943-958. doi: 10.1002/hep.30481. PMID: 30575985; PMCID: PMC6635738.

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1: Tran A, Koh TS, Prawira A, Ho RZW, Le TBU, Vu TC, Hartano S, Teo XQ, Chen WC, Lee P, Thng CH, Huynh H. Dynamic Contrast-Enhanced Magnetic Resonance Imaging as Imaging Biomarker for Vascular Normalization Effect of Infigratinib in High- FGFR-Expressing Hepatocellular Carcinoma Xenografts. Mol Imaging Biol. 2020 Sep 9. doi: 10.1007/s11307-020-01531-7. Epub ahead of print. PMID: 32909245.

2: Magone MT, Hartley IR, Fitzgibbon E, Bishop R, Arango M, Moran S, Vold R, Rivero JD, Pozo K, Streit J, Roszko KL, Collins MT, Gafni RI. Ocular Adverse Effects of Infigratinib, a New Fibroblast Growth Factor Receptor Tyrosine Kinase Inhibitor. Ophthalmology. 2020 Sep 1:S0161-6420(20)30844-7. doi: 10.1016/j.ophtha.2020.08.026. Epub ahead of print. PMID: 32888946.

3: Lyou Y, Grivas P, Rosenberg JE, Hoffman-Censits J, Quinn DI, P Petrylak D, Galsky M, Vaishampayan U, De Giorgi U, Gupta S, Burris H, Rearden J, Li A, Wang H, Reyes M, Moran S, Daneshmand S, Bajorin D, Pal SK. Hyperphosphatemia Secondary to the Selective Fibroblast Growth Factor Receptor 1-3 Inhibitor Infigratinib (BGJ398) Is Associated with Antitumor Efficacy in Fibroblast Growth Factor Receptor 3-altered Advanced/Metastatic Urothelial Carcinoma. Eur Urol. 2020 Aug 23:S0302-2838(20)30616-3. doi: 10.1016/j.eururo.2020.08.002. Epub ahead of print. PMID: 32847703.

4: Makawita S, K Abou-Alfa G, Roychowdhury S, Sadeghi S, Borbath I, Goyal L, Cohn A, Lamarca A, Oh DY, Macarulla T, T Shroff R, Howland M, Li A, Cho T, Pande A, Javle M. Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial. Future Oncol. 2020 Jun 25. doi: 10.2217/fon-2020-0299. Epub ahead of print. PMID: 32580579.

5: Pal SK, Bajorin D, Dizman N, Hoffman-Censits J, Quinn DI, Petrylak DP, Galsky MD, Vaishampayan U, De Giorgi U, Gupta S, Burris HA, Soifer HS, Li G, Wang H, Dambkowski CL, Moran S, Daneshmand S, Rosenberg JE. Infigratinib in upper tract urothelial carcinoma versus urothelial carcinoma of the bladder and its association with comprehensive genomic profiling and/or cell-free DNA results. Cancer. 2020 Jun 1;126(11):2597-2606. doi: 10.1002/cncr.32806. Epub 2020 Mar 24. PMID: 32208524; PMCID: PMC7515773.

6: Felix NS, de Mendonça L, Braga CL, da Silva JS, Samary CDS, Vieira JB, Cruz F, Rocha NN, Zapata-Sudo G, Rocco PRM, Silva PL. Effects of the FGF receptor-1 inhibitor, infigratinib, with or without sildenafil, in experimental pulmonary arterial hypertension. Br J Pharmacol. 2019 Dec;176(23):4462-4473. doi: 10.1111/bph.14807. Epub 2019 Dec 5. PMID: 31351013; PMCID: PMC6932937.

7: Huynh H, Lee LY, Goh KY, Ong R, Hao HX, Huang A, Wang Y, Graus Porta D, Chow P, Chung A. Infigratinib Mediates Vascular Normalization, Impairs Metastasis, and Improves Chemotherapy in Hepatocellular Carcinoma. Hepatology. 2019 Mar;69(3):943-958. doi: 10.1002/hep.30481. PMID: 30575985; PMCID: PMC6635738.



Additional Information

BGJ398 is a potent, selective and orally active pan-FGFR inhibitor, with IC50s of 0.9, 1.4, 1.0 and 60 nM for FGFR1, 2, 3 and 4, respectively.

CAS#872511-34-7 ( BGJ-398 free base); 1310746-11-2 (BGJ-398 monohydrate); 1310746-10-1 (BGJ-398 phosphate salt)