Table 5.

Examples of small molecular weight ligand-binding site comparisons relevant to medicinal chemistry.

Method	On-Target	Secondary Target	Ligand	Secondary Target Affinity	Ref.
SOIPPA	Estrogen receptor alpha	SERCA Ca2+ ion channel ATPase	Tamoxifen	IC50 = 5 µM	[168]
CPASS	Bcl-2 apoptosis protein Bcl-xL	Type III SS Needle Protein (PrgI)	Chelerythrine	N/A a	[160]
SOIPPA	Catechol-O-methyltransferase	Enoyl-acyl carrier protein reductase	Entacapone	IC50 = 80 µM	[162]
SiteAlign	Pim-1 kinase	Synapsin I	Quercetagetin	IC50 = 0.15 µM	[167]
SMAP	HIV-1 protease	ErbB2 receptor tyrosine kinase	Nelfinavir	N/A b	[163]
PSSC	Monoamine oxidase	Lysine-specific demethylase 1	Namoline	IC50 = 51 µM	[166]
SMAP	Epidermal growth factor	β-secretase	Gefitinib	IC50 = 20 µM	[165]
KRIPO	Cannabinoid type 1 receptor	Adenine nucleotide translocase 1	Ibipinabant	N/A c	[169]
PSIM	PPAR gamma	Cyclooxygenase type 1	Fenofibrate	IC50 = 950 μM	[161]
TM-align	Receptor Tyrosine kinases	Acetylcholinesterase	Pazopanib Sunitinib	IC50 = 0.93 μM IC50 = 5.87 μM	[164]
Shaper	Cyclooxygenase type 1	Cinnamoylesterase	Flurbiprofen	IC50 = 400 µM	[40]
ProCare	HIV-1 reverse transcriptase	TNF-α trimer	Efavirenz Delavirdine	Kd = 24 µM Kd = 49 µM	[159]

^a binding evidenced by ¹⁵N-¹H NMR-HSQC spectra; ^b 15% inhibition at 20 µM in a kinase activity assay; ^c 30% Inhibition of ANT-dependent mitochondrial ADP uptake at a concentration of 100 µM.