Peptide Receptor Targeting in Cancer: The Somatostatin Paradigm

Table 1

Binding affinities of native SST and synthetic agonists for SST receptor subtypes.

Ligands		Binding affinity (IC50 nM)
		sst1	sst2	sst3	sst4	sst5
Endogenous	SST-14	0.1–2.26	0.2–1.3	0.3–1.6	0.3–1.8	0.2–0.9
	SST-28	0.1–2.2	0.2–4.1	0.3–6.1	0.3–7.2	0.05–0.4
	CST-14	2.1	0.5	3.8	18.2	0.9
	CST-17	0.25–7.0	0.6–0.9	0.4–0.6	0.5–0.6	0.3–0.4
Synthetic peptides in clinical use	Octreotide	>1000	0.4–2.1	4.4–34.5	>1000	5.6–32
	Lanreotide	>1000	0.5–1.8	43–107	>1000	0.6–14
	Pasireotide	9.3	1	1.5	>100	0.16
Synthetic peptides in clinical trials	Vapreotide	>1000	0.2–5.4	31	45	0.7
	Somatoprim	>1000	3	>100	7	6
Synthetic peptides in experimental use	Seglitide	>1000	0.1–1.5	27–36	>1000	2–23
	BIM-23268	18.4	15.1	61.6	16.3	0.37
	BIM-23745	42	>1000	>1000	>1000	>1000
	BIM-23926	4	>1000	>1000	>1000	>1000
	BIM-23120	>1000	0.34	412	>1000	213,5
	BIM-23206	>1000	166	>1000	>1000	2.4
	BIM-23704	6.3	1.4	43.2	>1000	115
	BIM-23190	>1000	0.35	215	>1000	11.2
	BIM-23A799	2.5	0.3	0.6	>1000	0.6
	KE108	2.6	0.9	1.5	1.6	0.65
Nonpeptide agonists	L-797,591	1.4	1875	2240	170	>1000
	L-779,976	>1000	0.05	729	310	>1000
	L-796,778	>1000	>1000	24	>1000	>1000
	L-803,087	199	>1000	1280	0.7	>1000
	L-817,818	3.3	52	64	82	0.4
Chimeric SST/DA compounds	BIM-23A757^a	ND	0.58	ND	ND	104.4
	BIM-23760^b	622	0.03	160	>1000	42
	BIM-23A761^c	ND	0.01	ND	ND	3.7
Antagonists	ODN-8	>10000	>10000	6.7	>10000	>10000
	BN81658	>1000	>1000	1.58	>1000	>1000
	Cyn154806	>1000	3.6	150	650	20

High affinity for individual SST receptors is reported in bold.
D2R IC₅₀: ^a7.9, ^b15, ^c27 nM, ND: not determined.