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Erdafitinib(JNJ-42756493)

Names

[ CAS No. ]:
1346242-81-6

[ Name ]:
Erdafitinib(JNJ-42756493)

[Synonym ]:
JNJ-42756493
UNII:890E37NHMV
1,2-Ethanediamine, N-(3,5-dimethoxyphenyl)-N-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)-6-quinoxalinyl]-
N-(3,5-Dimethoxyphenyl)-N'-isopropyl-N-[3-(1-methyl-1H-pyrazol-4-yl)-6-quinoxalinyl]-1,2-ethanediamine
N1-(3,5-dimethoxyphenyl)-N1-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]-N2-(propan-2-yl)ethane-1,2-diamine
erdafitinib
N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine

Biological Activity

[Description]:

Erdafitinib (JNJ-42756493) is a potent and orally available FGFR family inhibitor; inhibits FGFR1/2/3/4 with IC50s of 1.2, 2.5, 3.0 and 5.7 nM, respectively.

[Related Catalog]:

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FGFR
Research Areas >> Cancer

[Target]

IC50: 1.2 nM (FGFR1), 2.5 nM (FGFR2), 3.0 nM (FGFR3)and 5.7 nM (FGFR4)[1]


[In Vitro]

Erdafitinib inhibits the tyrosine kinase activities of FGFR1-4 in time-resolved fluorescence assays with IC50 values of 1.2, 2.5, 3.0 and 5.7 nM, respectively. The closely related VEGFR2 kinase is less potently inhibited (30-fold less potent compared to FGFR1) by erdafitinib, with an IC50 value of 36.8 nM. JNJ-42756493 binds FGFR1, 3, 4, and 2 with Kd values of 0.24, 1.1, 1.4 and 2.2 nM, respectively. The Kd value for VEGFR2 is higher at 6.6 nM. JNJ-42756493 inhibits proliferation of FGFR1, 3, and 4 expressing cells with IC50 values of 22.1, 13.2, and 25nM, respectively[1].

[In Vivo]

In xenografts from human tumor cell lines or patient-derived tumor tissue with activating FGFR alterations, Erdafitinib administration results in potent and dose-dependent antitumor activity accompanied by pharmacodynamic modulation of phospho-FGFR and phospho-ERK in tumors[1].

[Cell Assay]

Erdafitinib is dissolved in DMSO. KATO III, RT-112, A-204, RT-4, DMS-114, A-427 and MDA-MB-453 cells are treated with erdafitinib (from 10 μM to 0.01 nM in 2% DMSO, final concentration). Following 4-day incubation, cell viability is determined using MTT reagent. The optical density is determined at 540 nm[1].

[Animal admin]

Mice: Mice bearing SNU-16 human gastric carcinoma (FGFR2 amplified) xenograft tumors are dosed orally with 0, 3, 10 or 30mg/kg JNJ-42756493. Tumor tissue and mouse plasma (3 mice per time point) are harvested at 0.5, 1, 3, 7, 16 and 24h post-dosing[1].

[References]

[1]. Perera TP, et al. Discovery and pharmacological characterization of JNJ-42756493 (erdafitinib), a functionally selective small molecule FGFR family inhibitor. Mol Cancer Ther. 2017 Mar 24. pii: molcanther.0589.2016.


[Related Small Molecules]

Nintedanib (BIBF 1120) | Infigratinib (BGJ398) | AZD4547 | PD173074 | FGF-401 | SU 5402 | Heparan Sulfate | Lucitanib | LY2784544 | BLU554 | Dovitinib (TKI-258, CHIR-258) | Rogaratinib | LY2874455 | BLU-9931 | KW-2449

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
662.3±55.0 °C at 760 mmHg

[ Molecular Formula ]:
C25H30N6O2

[ Molecular Weight ]:
446.545

[ Flash Point ]:
354.4±31.5 °C

[ Exact Mass ]:
446.243011

[ PSA ]:
77.33000

[ LogP ]:
3.60

[ Vapour Pressure ]:
0.0±2.0 mmHg at 25°C

[ Index of Refraction ]:
1.618

[ Storage condition ]:
-20℃

Related Compounds