Table 2.

Summary of selected RAS degraders

Compound	RAS Targets	Concentration	In vitro studies	In vivo studies	Ref(s).
RRSP	KRAS, NRAS, HRAS	1-300 pM	Induces apoptosis or senescence in pancreatic, breast, and colon cancer	Tumor regression in pancreatic, breast, and colon xenografts	115,116,117,118,119,120
ASP3082	PROTAC against KRAS G12D	NA	ND	In vivo results not disclosed but a phase I clinical trial began in June 2022	112,113,114
RC-U	KRAS, NRAS, HRAS	transfection	Reduced RAS levels upon transfection in HEK293T cells	Transfection reduced tumor size	121
VHL-KRAS DARPin K19	KRAS	transfection	Reduced KRAS levels in mutant KRAS cells	Doxycycline-inducible expression reduced tumor size	122
UBOX-Pan-RAS iDab	KRAS, NRAS, HRAS	transfection	Reduced RAS levels in mutant KRAS cells	Doxycycline-inducible expression reduced tumor size	122
BIpanKRAS3	KRAS, KRAS G12D	19–91 nM	Cleaved KRAS and reduced pERK levels in NCI-H2122 and SW837 cells	KRASG12/13D mutant CDX xenograft models a 30-mg/kg dose caused tumor regression	84,111
Compound 13 (XY-4-88)	KRAS G12C	>0.410 μM	Did not degrade endogenous RAS	NA	109
LC-2	KRAS G12C	0.25–0.76 μM	Degraded endogenous KRASG12C and ERK	NA	110
FKBP12F36V-KRASG12V + dTAG13	KRAS G12V	transfection	Reduced KRAS G12V levels	NA	123
VHL-aHRAS AdPROM	KRAS, NRAS, HRAS	transfection	Reduced K,N,H-RAS in CRISPR-Cas9 HEK293 and U2OS cells	NA	124
DARPin K27-SPOP and others	various	plasmid and mRNA transfection	Several RAS degraders and E3 ligases reduced RAS expression and inhibited cell proliferation specific to each compound	NA	74
BIKRASdegrader1	KRAS mutants	2–116 nM	Degraded KRAS, reduced pERK levels and reduced cell proliferation	NA	111
Engineered subtilisin	KRAS	transfection	Cleaved eGFP-KRAS after doxycycline induction	NA	125

ND-not disclosed, NA-information is not available