Table 1.

Anti-RAS biologics.

Biologic	Name	Mechanism of action	Binding specificity	Affinity (KD)	References
Antibodies	Y13–259	RAS sequestration, delocalization from membrane	a.a. 70–81 of HRAS	N/A	Mulcahy, Smith, and Stacey (1985)
	anti-p21ser	Inhibition of nucleotide binding	Ser12 of KRAS (G12S)	N/A	Clark, Wong, Arnheim, Nitecki, and McCormick (1985)
Intrabodies	scFv Y13–259	RAS sequestration, delocalization from membrane	a.a. 70–81 of HRAS	N/A	Cardinale, Lener, Messina, Cattaneo, and Biocca (1998)
	iDab#6	Blocks effector binding	Switch regions of GTP-loaded HRAS	6.2 nM	Tanaka, Lobato, and Rabbitts (2003)
	KGHV500	Cytokine-induced killer (CIK) cell-mediated, tumor-specific delivery	pan-RAS	N/A	Wang et al. (2018)
	inRas37	Tumor-specific, cell-penetrating, full-length antibody	GTP-loaded RAS	N/A	Shin et al. (2020)
Monobodies	NS1	Allosteric disruption of dimerization/nanoclustering; inhibits GTP loading on WT	α4-α5 region of H/KRAS	13–16nM (HRAS); 60–67 nM (kRAS)	Spencer-Smith et al. (2017)
	12VC1	Blocks effector binding	Switch regions and mutant residues of KRAS (G12V/C)	100nM	Teng et al. (2021)
	RasIn2	Blocks effector binding	Switch I of GTP-loaded RAS	120nM	Cetin et al. (2017)
DARPins	K27	Blocks nucleotide exchange	GDP-loaded RAS	4nM	Guillard et al. (2017)
	K55	Blocks effector binding	GTP-loaded RAS	167nM	Guillard et al. (2017)
	K13	Blocks effector binding, nucleotide exchange, and dimerization/nanoclustering	α3-α4 (His95) region of KRAS	30 nM	Bery et al. (2019)
	K19	Blocks effector binding, nucleotide exchange, and dimerization/nanoclustering	α3-α4 (His95) region of KRAS	10 nM	Bery et al. (2019)
Sso7d	R11.1.6	Blocks effector binding	Switch regions; specific RAS (G12) mutants	2–6nM	Kauke et al. (2017)
Miniproteins	225–15 a/b	Blocks effector binding	Binds as a dimer to RAS	60 ± 20 pM for KRAS-GppNHp	McGee et al. (2018)
Toxin Peptidases	RRSP	Cleaves Switch I region of RAS; blocks effector binding	Cleaves between Y32 and D33 of Switch I	N/A	Antic, Biancucci, Zhu, Gius, and Satchell (2015)
Cyclic Peptides	Compound 12	Blocks effector binding	Not specified	0.83 μM for KRAS	Wu, Upadhyaya, Villalona-Calero, Briesewitz, and Pei (2013)
	Cyclorasin 9A5	Blocks effector binding	Switch I of GTP-loaded RAS	0.44 μM for GTP-bound KRAS; 2.5 μM for GDP-bound KRAS	Upadhyaya et al. (2015)
	KS-58	Blocks nucleotide exchange/binding; competes with SOS1 GEF binding	KRAS (G12D)-selective	N/A	Sakamoto, Masutani, and Hirokawa (2020)
	KD2	Blocks effector binding	Switch II groove of GTP-loaded KRAS (G12D)	N/A	Zhang et al. (2020)
Stapled peptides	SAH-SOS1	Blocks nucleotide exchange/binding	Switch regions	100–175 nM for KRAS	Leshchiner et al. (2015)