Table 2.

Summary of the inhibitory activities of ADAM17 inhibitors.

Compound Numbera	Chemical Name or Product Name	IC50 Valueb	Reference
Hydroxamate-based small-molecule compounds:
1	Marimastat	4.75 μM	(102)
2	Apratastat	144 ng/mL (in vitro); 81.7ng/mL (ex vivo)	(250)
3	Aderbasib/INCB7839	N.D.	(251)
4	INCB3619	14 nM	(252)
5	KP-457	10.6 nM	(253)
6	GW280264X	N.D.	(4, 201, 254)
7	PF-5480090/TMI-002	~1696.5 RFu/mg	(255)
8	GI254023X	541 μM	(256)
9	Batimastat	N.D.	(257)
10	TAPT-1	8.09 μM	(107)
11	(2R)-N-hydroxy-2-[(3S)-3-methyl-3-{4-[(2-methylquinolin-4-yl)methoxy]phenyl}-2-oxopyrrolidin-1-yl]propanamide	N.D.	(20)
12	(3S)-4-{[4-(but-2-ynyloxy)phenyl]sulfonyl}-N-hydroxy-2,2-dimethylthiomorpholine-3-carboxamide	N.D.	(20)
13	(3S)-4-{[4-(but-2-ynyloxy)phenyl]sulfonyl}-N-hydroxy-2,2-dimethylthiomorpholine-3-carboxamide	N.D.	(20)
14	Methyl (1R,2S)-2-(hydroxycarbamoyl)-1-{4-[(2-methylquinolin-4-yl)methoxy]benzyl}cyclopropanecarboxylate	N.D.	(20)
15	BMS-561392	0.20 nM	(258)
Non-hydroxamate-based small-molecule compounds:
16	ZLDI-8	6.85 μM	(259)
17	SN-4	3.22 μM	(102)
18	SN-4(Nps)2	N.D.	(102)
19	JTP-96193	5.4 nM	(258)
20	(1S,3R,6S)-4-oxo-6-{4-[(2-phenylquinolin-4-yl)methoxy]phenyl}-5-azaspiro[2.4]heptane-1-carboxylic acid	N.D.	(20)
21	N-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}-5-methyl-D-tryptophan	N.D.	(20)
22	(3S)-1-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}pyrrolidine-3-thiol	N.D.	(20)
23	3-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}propane-1-thiol	N.D.	(20)
Anti-ADAM17 monoclonal antibodies:
	A300E	~0.7 μg/mL	(260)
	A9(B8)	0.22 nM (human); 0.25 nM (mouse)	(261)
	D1(A12)	4.7 nM	(262)
	MEDI3622	39 pmol/L (human); 132 pmol/L (mouse)	(263)

^aSee Figure 4 ; ^bN.D. refers to not detected.