Table 2.

Ongoing clinical evaluation of anti-FGFR drugs with IC50< 100 nmol against at least one FGFR

Targets and IC50, nmol/L (if available)
CompoundFGFR1FGFR2FGFR3FGFR4VEGFR1VEGFR2VEGFR3PDGFR-αPDGFR-βOthers [IC50, nmol/L]Clinical developmentCompany
MultitargetedTKIs
TKI258 (dovitinib; ref. 64)891013820027FLT-3 [1]Phase III (RCC)Novartis
KIT [2]
CSF-1 [36]
BIBF1120 (nintedanib; ref. 65)69371086103421135965LCK [16]Phase III (NSCLC, ovarian)Boehringer-Ingelheim
FLT-3 [26]
SRC [156]
LYN [195]
E3810 (66)17.582.5237.5>1,00072510175525CSF-1 [5]Phase 1 (solid tumors)Ethical Oncology of Science
KIT [456]
E7080 (lenvat-inib; ref. 67)462245.25139KIT [100]Phase III (thyroid)Eisai
BMS582664 (brivanib; ref. 68)148125683802510>6,000Phase III (HCC, CRC)Bristol-Myers Squibb
ENMD-2076 (69)9371500581656.4FLT-3 [2]Phase II (breast, ovarian)Entremed
RET [10.4]
SRC [20.2]
CSF-1 [24.8]
Aurora A [14]
Aurora B [350]
KIT [120]
TSU68 (orantinib; ref. 70)1.2μmol/L2.1 μmol/L0.008 μmol/LPhase III (HCC)Taiho Pharmaceutical
AP24534 (ponatinib; ref. 71)221881.51.1ABL [0.7]Phase II (ALL, CML)Ariad
SRC [5.4]
LYN [0.24]
KIT [12.5]
Selective TKIs
AZD4547 (72)0.22.51.816524IGFR [581]Phase II (breast, gastric)AstraZeneca
BGJ398 (73)0.91.4160Phase 1 (solid tumors)Novartis
LY2874455 (74)2.82.66.467aPhase 1 (solid tumors)Eli Lilly
Monoclonal antibodies
MGFR1877S [cl in icalt rials.gov]Phase I (MM, solid tumors)Genentech
FGF traps
HGS1036/FP-1039(75)FGF1Phase I (solid tumors)Human Genomic Sciences
FGF2
FGF4

aSix- to 9-fold cellular and in vivo selectivity on inhibition of FGF- over VEGF-mediated target signaling in mice.

Abbreviations: ALL, acute lymphoblastic leukemia: CML, chronic myeloid leukemia: CRC, colorectal cancer: FLT-3, Fms-like tyrosine kinase receptor 3: HCC, hepatocellular carcinoma: IGFR, insulin-like growth factor receptor: MM, multiple myeloma: RCC, renal cell carcinoma: STS, soft tissue sarcoma.