BGJ398
NVP-BGJ398 is a potent, selective, and orally bioavailable inhibitor of the FGFR tyrosine kinases. NVP-BGJ398 is a small molecular with the formula of C26H31Cl2N7O3 and Molecular Weight of 560. The fibroblast growth factor receptor 1 (FGFR1), FGFR2, FGFR3, and FGFR4, encompasses the receptors for 18 different FGF ligands. These ligand–receptor combinations regulate a broad spectrum of signaling during development and in normal growth control. BGJ398 inhibits the cell proliferation and induces apoptosis in cancer cells and suppresses tumor growth in xenograft model.
References:
1. Fibroblast Growth Factor Receptors as Novel Therapeutic Targets in SNF5-Deleted Malignant Rhabdoid Tumors. S W?hrle, A Weiss, M Ito, A Kauffmann, M Murakami. PLOS ONE. 2013
2. Rescue screens with secreted proteins reveal compensatory potential of receptor tyrosine kinases in driving cancer growth. F Harbinski, VJ Craig, S Sanghavi, D Jeffery, L Liu. Cancer Discovery, 2012
- 1. Ying Zhang, Qian Fang, et al. "Increased FGFR3 is involved in T-2 toxin-induced lesions of hypertrophic cartilage associated with endemic osteoarthritis." Hum Exp Toxicol. 2023 Jan-Dec:42:9603271231219480. PMID: 38059300
- 2. Longwei Hu, Yang Wang, et al. "Apoptosis repressor with caspase recruitment domain (ARC) promotes bone regeneration of bone marrow-derived mesenchymal stem cells by activating Fgf-2/PI3K/Akt signaling." Stem Cell Res Ther. 2021 Mar 16;12(1):185. PMID:33726822
- 3. Day EK, Sosale NG, et al. "Glioblastoma Cell Resistance to EGFR and MET Inhibition Can Be Overcome via Blockade of FGFR-SPRY2 Bypass Signaling." Cell Rep. 2020;30(10):3383-3396.e7. PMID:32160544
- 4. Serra M, Alysandratos KD, et al."Pluripotent stem cell differentiation reveals distinct developmental pathways regulating lung- versus thyroid-lineage specification." Development. 2017 Nov 1;144(21):3879-3893. PMID:28947536
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 560.48 |
| Cas No. | 872511-34-7 |
| Formula | C26H31Cl2N7O3 |
| Synonyms | BGJ398,BGJ-398 |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥7 mg/mL in DMSO with gentle warming |
| Chemical Name | 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-[6-[4-(4-ethylpiperazin-1-yl)anilino]pyrimidin-4-yl]-1-methylurea |
| SDF | Download SDF |
| Canonical SMILES | CCN1CCN(CC1)C2=CC=C(C=C2)NC3=CC(=NC=N3)N(C)C(=O)NC4=C(C(=CC(=C4Cl)OC)OC)Cl |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
AN3CA, MFE296, MFE280, SNGM and HEC1A cells |
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Preparation method |
The solubility of this compound in DMSO is |
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Reaction Conditions |
0.5 μM, 72 hours |
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Applications |
Exposure of AN3CA, MFE296, and MFE280 cells to the inhibitor led to a significant increase in the fraction of cells in G0–G1 arrest and to a significant increase in the fraction of cells undergoing apoptosis, when compared with untreated controls. In contrast, NVP-BGJ398 treatment did not alter the fractions of cells in G0–G1 arrest in the FGFR2 wild-type endometrial cancer cell lines SNGM or HEC1A in vitro. Moreover, NVP-BGJ398 treatment had no effect on apoptosis in the FGFR2 wild-type endometrial cancer cell line HEC1A. |
| Animal experiment: [1] | |
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Animal models |
Nude mice bearing AN3CA, MFE296, SNGM or HEC1A xenografts |
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Dosage form |
Oral administration, 30 or 50 mg/kg, daily |
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Applications |
NVP-BGJ398 significantly delayed the growth of FGFR2-mutated endometrial cancer xenograft tumors. In contrast, NVP-BGJ398 had no in vivo inhibitory effects in the long-term study using the FGFR2 wild-type endometrial cancer cell line SNGM, but surprisingly did show in vivo activity in HEC1A cells by delaying tumor growth in these cells. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Konecny G E, Kolarova T, O'Brien N A, et al. Activity of the fibroblast growth factor receptor inhibitors dovitinib (TKI258) and NVP-BGJ398 in human endometrial cancer cells. Molecular cancer therapeutics, 2013, 12(5): 632-642. |
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| Description | BGJ398 (NVP-BGJ398) is a potent and selective inhibitor of FGFR for FGFR1/2/3 with IC50 of 0.9 nM/1.4 nM/1 nM, >40-fold selective for FGFR versus FGFR4 and VEGFR2, and little activity to Abl, Fyn, Kit, Lck, Lyn and Yes. | |||||
| Targets | FGFR1 | FGFR2 | FGFR3 | FGFR4 | ||
| IC50 | 0.9 nM | 1.4 nM | 1 nM | 60 nM | ||
Quality Control & MSDS
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