Table 2.

Eph/ephrin targeting molecules

Molecules	Targets	Activity	Ref.
Kinase inhibitors
anilinopyrimidine derivatives	EPHB4a	ATP competitors	133, 211
benzenesulfonamide derivative	EPHB4a	ATP competitor	132
XL647 (EXEL-7647)b	EPHB4a	ATP competitor	212
xanthine derivatives	Eph receptors	ATP competitors	135, 213
LDN-211904	Eph receptors	ATP competitor	136
pyrido[2,3-d]pyrimidine PD173955	Eph receptors	ATP competitor	214
nilotinib and analogsb	Eph receptors	ATP competitors	134, 215
dasatiniba	Eph receptors	ATP competitor	34, 35, 137, 138
Inhibitors of Eph expression
siRNA	EPHA2	mRNA downregulation	101, 102, 139
oligonucleotides	EPHA2	protein downregulation	100
siRNA	EPHB4	mRNA downregulation	36, 37, 194, 216, 217
oligonucleotides	EPHB4	Protein downregulation	36, 194, 216, 217
Inhibitors of Eph-ephrin interaction
EPHA2 Fc, EPHA3 Fc	EPHRIN-A	Eph competitor	53, 218–220
sEPHB4	EPHRIN-B	Eph competitor	142, 221, 222
KYL and other peptidese	EPHA4	ephrin competitor	147, 150, 223
SNEW and other peptides	EPHB2	ephrin competitor	145, 149
TNYL-RAW peptide	EPHB4	ephrin competitor	145, 148, 224
dimethyl-pyrrole derivatives	EPHA2, EPHA4	ephrin competitor	150, 151
mAb 2H9 antagonistic antibody	EPHB2	ephrin competitor	143
Activators of Eph forward signaling (also downregulate Eph expression)
EA1.2 antibody	EPHA2	Eph activation/degradation, ADCCC?	100
EA2, B233, 3F2-WT (humanized B233) antibody	EPHA2	Eph activation/degradation, ADCC?	152, 155
EA5 antibody	EPHA2	Eph activation/degradation, reduced Src phosphorylation & VEGF levels, ADCC?	153
Ab20, 1G9-H7 antibodiesd	EPHA2	Eph activation/degradation	156
mAB208	EPHA2	Eph degradation & enhanced presentation of peptide antigens on tumor cell surface	154
YSA, SWL peptides	EPHA2	ephrin competitor, Eph activation/degradation	146
dimerized IIIA4 antibody	EPHA3	Eph activation	161
EPHRIN-A1 Fc	EphA receptors	Eph activation/degradation	74
EPHRIN-B2 Fc	EPHB4	Eph activation/degradation	127
Cytotoxic molecules
1C1 antibody-mc-MMAFf conjugateb	EPHA2	receptor-mediated internalization & disruption of microtubule dynamics	157, 158
3F2-3M antibody (mutated 3F2-WT with enhanced effector function)	EPHA2	ADCC	155
bscEphA2xCD3 bispecific single-chain antibody	EPHA2/CD3	redirection of unstimulated cytotoxic T cells to EphA2-positive tumor cells	162
YSA-modified adenoviruse	EPHA2	adenoviral transduction of EphA2-expressing tumor cells	225
EPHRIN-A1-PE38QQR Pseudomonas exotoxin A conjugate	EphA receptors	EphA-mediated internalization and exotoxin-dependent cell death	226
EPHRIN-A1-gold-coated nanoshells	EphA receptors	absorption of near infrared light for photothermal ablation of tumor cells	159
2H9 antibody-vc-MMAEg conjugate	EPHB2	receptor-mediated internalization & disruption of microtubule dynamics	143
Imaging agents
64Cu-DOTA-1C1 antibody	EPHA2	binding, which enables radioimmunoPET	160
YSA peptide-magnetic nanoparticles	EPHA2	binding, which enables cell capture	227, 228
111Indium-labelled IIIA4 antibody	EPHA3	binding to low affinity ephrin-binding site, which enables tumor detection	161

^aEph receptor selectivity has not been reported

^bIn clinical trials

^CADCC, antibody-dependent cell-mediated cytotoxicity

^dnot effective in vivo

^etested in vivo in a model of spinal cord injury

^fmc-MMAF, stable maleimidocaproyl linker-monomethylauristatin F

^gvc-MMAE, cathepsin B-cleavable valine-citrulline linker-monomethylauristatin E..