Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors
Abstract
:1. Introduction
2. Organization of FGFR
3. Structure of FGFR Kinase Domain
4. Characteristics of FGFR/Inhibitor Interaction
5. Current Status of Small Molecule FGFR Inhibitor Development
6. FGFR Gatekeeper Mutation and Drug Resistance
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Inhibitor Name | Binding Features | IC50 (nM) | PDB ID | Clinical Trial Phase/Number | Reference |
---|---|---|---|---|---|
JNJ-42756493 (Erdafitinib) | Pan-FGFR Reversible Type I | FGFR1: 1.2 FGFR2: 2.5 FGFR3: 3.0 FGFR4: 5.7 | n/a | FDA approved | [15] |
AZD4547 | Pan-FGFR Reversible Type I | FGFR1: 0.2 FGFR2: 2.5 FGFR3: 1.8 FGFR4: 165 | 4V05 | Phase I/II NCT02824133 | [14,34] |
Ly2874455 | Pan-FGFR Reversible Type I | FGFR1: 2.8 FGFR2: 2.6 FGFR3: 6.4 FGFR4: 6 | 5JKG | Phase I NCT01212107 | [33,48] |
CH5183284 | Pan-FGFR Reversible Type I | FGFR1: 9.3 FGFR2: 7.6 FGFR3: 22 FGFR4: 290 | 5N7V | Phase II/III NCT03344536 | [49] |
NVP-BGJ398 | Pan-FGFR Reversible Type I | FGFR1: 0.9 FGFR2: 1.4 FGFR3: 1 FGFR4: 60 | 3TT0 | Phase II NCT02706691 | [50] |
INCB054828 | Pan-FGFR Reversible Type I | FGFR1: 0.4 FGFR2: 0.5 FGFR3: 1.2 FGFR4: 30 | n/a | Phase II NCT03011372 | [51] |
Rogaratinib | Pan-FGFR Reversible Type I | FGFR1: 12–15 FGFR2: <1 FGFR3: 19 FGFR4: 33 | n/a | Phase II/III NCT03410693 | [52] |
PRN1371 | Pan-FGFR Irreversible Type I | FGFR1: 0.6 FGFR2: 1.3 FGFR3: 4.1 FGFR4: 19.3 | n/a | Phase I NCT02608125 | [53] |
TAS-120 | Pan-FGFR Irreversible Type I | FGFR1: 3.9 FGFR2: 1.3 FGFR3: 1.6 FGFR4: 8.3 | 6M2Q | Phase I/II NCT02052778 | [54] |
BLU-554 | FGFR4 selective Irreversible, Type I | FGFR1: 624 FGFR2: 1202 FGFR3: 2203 FGFR4: 5 | n/a | Phase I NCT02508467 | [55] |
H3B-6527 | FGFR4 selective Irreversible, Type I | FGFR1: 320 FGFR2: 1290 FGFR3: 1060 FGFR4: <1.2 | 5VND | Phase I NCT02834780 | [56] |
FGF401 | FGFR4 selective Reversible Covalent, Type I | FGFR1-3: >10,000 FGFR4: 1.1 | 6JPJ | Phase I/II NCT02325739 | [13,57] |
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Dai, S.; Zhou, Z.; Chen, Z.; Xu, G.; Chen, Y. Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors. Cells 2019, 8, 614. https://doi.org/10.3390/cells8060614
Dai S, Zhou Z, Chen Z, Xu G, Chen Y. Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors. Cells. 2019; 8(6):614. https://doi.org/10.3390/cells8060614
Chicago/Turabian StyleDai, Shuyan, Zhan Zhou, Zhuchu Chen, Guangyu Xu, and Yongheng Chen. 2019. "Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors" Cells 8, no. 6: 614. https://doi.org/10.3390/cells8060614
APA StyleDai, S., Zhou, Z., Chen, Z., Xu, G., & Chen, Y. (2019). Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors. Cells, 8(6), 614. https://doi.org/10.3390/cells8060614