Table 1.

New KRAS^G12D inhibitors under development and investigation

Drug	Sponsor	Properties	Status	Reference
ASP3082	Astellas	Binds to and targets KRASG12D for proteasome-mediated degradation	Phase I (NCT05382559)	Nagashima et al. (67)
HRS-4642	Hengrui Medicine	KRASG12D inhibitor	Phase I (NCT05533463)
RMC-9805 (RM-036)	Revolution Medicines	Covalent, GTP-bound and orally bioavailable KRASG12D(ON) inhibitor	IND-enabling	Jang et al. (68)
BI-2582	Boehringer Ingelheim	Non-covalent KRASG12D inhibitor, with nanomolar binding affinity to GTP-bound KRASG12D.	Preclinical	Tran et al. (69)
ERAS-4	Erasca	KRASG12D inhibitor	Preclinical	GlobeNewswire - 23 Aug 2022
THZ835	Tsinghua University	Inhibitor forms a salt bridge with Asp 12 of KRASG12D, induces switch-II fit pocket in KRASG12D and has off-target effect because inhibition is not fully dependent on KRAS mutation status.	Preclinical	Mao et al. (70)
QTX3046	Quanta Therapeutics	Non-covalent and orally bioavailable KRASG12D inhibitor, picomolar-level binding affinity (0.01nM) to inactive KRASG12D	Preclinical	Vo et al. (71)
QTX3034	Quanta Therapeutics	Selective, orally bioavailable, and picomolar-level binding affinity (0.6 nM) to GDP-bound KRASG12D	Preclinical	Zhang et al. (72)
VRTX153		Selective KRASG12D inhibitor that binds to GDP-bound state, with a nanomolar-level IC50.	Preclinical	Bhavar et al. (73)
Compound 3		KRASG12D inhibitor with IC50 at nanomolar-level.	preclinical	Wang et al. (74)
MRC-6236	Revolution Medicines	Orally bioavailable, selective inhibitor for active RAS (ON) form of both wild and mutant variants of the canonical RAS isoforms (HRAS, NRAS, and KRAS) (pan-RAS/ RASMULTI inhibitor).	Phase I (NCT05379985)	Gustafson et al. (65)
JAB-23425	Jacobio	Orally bioavailable, selective multiple KRAS mutant (G12A/C/D/R/V and Q61H) inhibitor, with sub-nanomolar-level binding affinity to GDP- and GTP-bound KRAS states. No inhibition of HRAS and NRAS (pan-KRAS/ RASMULTI inhibitor).	Preclinical	Wang et al. (75)
BI-2865	Boehringer Ingelheim	Non-covalent, selective inactive form of KRAS (both wild and mutant) inhibitor, no effect on HRAS and NRAS (pan-KRAS or RASMULTI inhibitor)	Preclinical	Kim et al. (66)

GTP, guanosine-5′-triphosphate; GDP, guanosine-5′-diphosphate; IND, investigative new drug.