Table 4.

Summary of the small molecules and biologics listed in this review.

	Section	Target	Method	Cmpd ID	Potency	Potency measure	Selectivity targets measured	Protein Cmpd Structure	PAINs?
Small molecules
Ras	4.1	Ras	A	1	IC50 0.5 μm	Competition assay	0	No	No
	4.1	Ras	A	2	IC50 0.7 μm	Competition assay	0	NMR	No
	4.1	Ras	A	3	IC50 90 μm	Fluorescence	0	No	No
	4.1	KRas	A	4	IC50 342 μm	Fluorescence	2	X‐Ray	No
	4.1	KRas	A	5	K D 190 μm	NMR	0	X‐Ray	No
	4.1	Rheb KRas	A	6	K D 1800 μm K D 600 μm	NMR	1	NMR	No
	4.1	KRas	A	7	K D 5.8 mm	NMR	0	NMR	No
	4.1	Ras	A	8	GI50 4‐7 μm	Cell phenotype	0	Docking	No
	4.1	KRas G12C	A	9	IC50 1.6 μm	Cellular target engagement	Proteome	X‐Ray	No
	4.1	KRas G12C	A	10**	IC50 120 nm	Cellular target engagement	Proteome	X‐Ray	No
	4.1	RalA,‐B	A	11	n.d.	ELISA/cell phenotype	0	Docking	No
	4.1	RalA,‐B	A	12	IC50 ≈3.5 μm	Cell phenotype	0	NMR	No
	4.1	RalA,‐B	A	13	K D 4.7 μm K D 7.7 μm	SPR ITC	2	NMR	No
	4.3	Sos	B	14	K D 7 μm	MST	1	Docking	Yes
	4.3	Sos	B	15	IC50 5 μm	Fluorescence	1	Docking	No
	4.3	Sos	B	16	IC50 32 μm	Fluorescence	1	Docking	No
	4.3	Epac1	B	17	IC50 71 μm	Cell phenotype	2	Docking	Yes
	4.3	Epac1	B	18	IC50 4 μm	Cell phenotype	2	Docking	Yes
	4.3	Kras/Sos1	B	19	n.d[b]	SPR	0	Xray	No
	4.3	Sos1	B	20	K D 450 nm IC50 320 nm	ITC Fluorescence	>100	Xray	No
	4.3	Sos1	B	21*	IC50 21 nm	Fluorescence	5	XRay	No
	4.4	Epac	C	22	IC50 8.4 μm	Fluorescence	2	No	No
	4.4	Epac	C	23	IC50 4 μm	Fluorescence	2	No	No
	4.4	Epac	C	24	IC50 5.9 μm	Fluorescence	2	Docking	No
	4.4	Epac2	C	25	IC50 0.4 μm	Fluorescence	2	No	No
	4.4	Epac1 Epac2	C	26	IC50 11 μm IC50 2.4 μm	Fluorescence	2	Docking	Yes
	4.4	Epac1	C	27	IC50 23 μm	Fluorescence	2	No	No
	4.5	KRas/Sos	D	28–31	n.d[a]	n/a	0	X‐Ray	No
	4.5	Ras/Sos	D	32	EC50 14 μm	Fluorescence	0	X‐Ray	No
	4.5	Ras/Sos	D	33	EC50 9 μm	Fluorescence	0	X‐Ray	No
	4.6	p21ras	E	34	n.d.[b]	Fluorescence	2	No	No
	4.6	KRas	E	35	K D ≈0.8 μm	SPR	5	No	No
	4.6	Ras	E	36	IC50 20 μm	Fluorescence	7	NMR	Yes
	4.6	Ras	E	37	IC50 100 μm	Fluorescence	7	NMR	Yes
Rho	5.1	Rac1	A	38	IC50 ≈50 μm	Pull‐down assay	6	X‐Ray	No
	5.1	Rac1	A	39	IC50 12 μm	G‐LISA[c]	2	Docking	Similar to aggregators
	5.1	Rac1	A	40	IC50 61 μm	Cell phenotype	1	Docking	No
	5.1	Rac1	A	41	IC50 4 μm	Cell phenotype	1	Docking	No
	5.1	Rac1	A	42	IC50 2.5 μm	G‐LISA[c]	1	Docking	No
	5.1	Rac1/3	A	43	IC50 1.1 μm	G‐LISA[c]	3	Docking	No
	5.1	Rac1 Cdc42	A	44	IC50 103 nm IC50 78 nm	G‐LISA[c]	2	Docking	No
	5.1	Rac1 Cdc42	A	45	n.d[b]	G‐LISA[c]	2	No	No
	5.1	Cdc42	A	46	n.d[b]	G‐LISA[c] Fluorescence	2	No	No
	5.1	Cdc42	A	47	K D 6.4 μm K D 11.4 μm	Fluorescence SPR	2	Docking	No
	5.1	RhoA (RhoB,C)	A	48	K D 354 nm	MST	5	Docking	No
	5.2	Trio	B	49	IC50 116 μm	Fluorescence	2	No	Toxic
	5.2	Trio	B	50	IC50 51 μm	Fluorescence	2	No	(May be toxic)
	5.2	Trio	B	51	IC50 56 μm	Fluorescence	2	No	(May be toxic)
	5.2	Trio	B	52	IC50 76 μm	Fluorescence	3	No	Yes
	5.2	LARG	B	53	K D 76 nm	MST	5	Docking	Yes
	5.2	DOCK2 DOCK1/5	B	54	IC50 23 μm	Fluorescence	5	No	Yes
	5.2	DOCK5 DOCK1/2	B	55	n.d.[b]	G‐LISA Fluorescence	3	No	No
	5.3	RhoGDI1/Cdc42	G	56	IC50 ≈12 μm	Cell phenotype	0	No	No
	5.4	MgcRac GAP/ Rac1	H	57	IC50 15 μm	Colorimetric	2	No	No
Arf	6.1	Arf1/ARF6	A	58	IC50 1 μm [d] IC50 3.4 μm [d]	Fluorescence Radiometric	8	Docking	No
	6.2	Arf1 or Arf5/BFA‐ sensitive GEF	D	59	K iapp ≈12 μm	Fluorescence	>10	XRay	No
	6.2	Arf1‐GDP/ARNO	D	60	K iapp 50 μm	Fluorescence	7	NMR	No
	6.2	Arf/ ArfGEF	D	61	GI50 12 nm EC50 27 nm	Cell phenotype	7	MD	No
	6.3	Cyto‐hesins	B	62	IC50 2.4–5.6 μm [d]	Fluorescence	>10	No	No
	6.3	Cyto‐hesins	B	63	IC50 3.1 μm	Fluorescence	1	No	No
	6.3	Cyto‐hesins	B	64	IC50 440 nm	Fluorescence	0	No	Similarity to aggregators
	6.3	GBF1	B	65	IC50 3.3 μm	Cell phenotype	1	No	Yes
	6.3	GBF1	B	66	IC50 3.4 μm	Cell phenotype	1	No	No
	6.3	GBF1	B	67	n.d	Cell phenotype	2	Docking	Yes
	6.3	GBF1	B	68	n.d	Cell phenotype	2	Docking	Yes
	6.3	ARNO	B	69	K iapp 3.7 mm	Fluorescence	0	X‐Ray	No
	6.3	ARNO	B	70	K iapp 1.6 mm	Fluorescence	0	X‐Ray	No
	6.4	ARFGAP	I	71	K D 670 nm	SPR	14	No	No
Biologics
	4.2	Ras	A	HBS3	KD 28 μm	Fluorescence polarization	0	NMR	No
	4.2	Ras	A	SAH‐SOS1 A	EC50 100–175 nm	Fluorescence polarization	0	NMR	No
	4.2	KRas‐G12D	A	KRpep‐2 d	1.6 nm	FRET	2	X‐Ray	No
	4.7	Ras	J	NF1‐S	IC50 87 μm	Radiolabeled competition	0	No	No
	6.3	Small ArfGEFs	B	M69	KD 16 nm	Filter binding assay	2	No	No

[a] Potency not determined as covalent compounds. [b] Assays conducted but specific potency (IC₅₀, K _D, K _iapp) not stated. [c] Cell‐based activation assay for small GTPases. [d] IC₅₀ could not be replicated in separate study due to poor solubility. * Suitable for use as a probe in vitro. ** Suitable for use as a probe in vitro and in vivo. Probe criteria: IC₅₀ or K _D <100 nm, >30‐fold selectivity against sequence‐related proteins of the same target family, profiled against relevant off‐targets and on‐target effects in cells at <1 μm concentration.