KRAS G12D inhibitor 1 (example 243) is an inhibitor of KRAS G12D with an IC 50 of 0.8 nM for KRAS G12D-mediated ERK phosphorylation [1].

MRTX1133 is a highly selective, first-in-class inhibitor of KRAS G12D. MRTX1133 targets the KRAS G12D protein in both active and inactive states. MRTX1133 selectively inhibits KRAS G12D mutant, but not KRAS wild-type, tumor cells[1][2]. MRTX1133 demonstrates dose-dependent inhibition of the KRAS pathway tumor regression in G12D mutant tumor models[2]. [1]. Xiaolun Wang, et al.Kras g12d inhibitors.WO2021041671A1.[2]. KRAS G12D Inhibitor: MRTX1133. [(accessed on 22 April 2021)];2021 Available online.

LUNA18 is an orally active inhibitor targeting KRAS, exhibiting potent activity with an IC50 value of less than 2 nM against the KRAS G12D-SOS mutation. It is utilized in cancer research [1].

Kras4B G12D-IN-1 is an anticancer agent that functions as an inhibitor of the Kras4B G12D protein. It effectively reduces the expression of Kras protein in mouse embryonic fibroblasts (MEFs) harboring the Kras4B G12D mutation[1].

KRAS G12D Inhibitor 17 (example 8), a quinazoline-linked (4R)-4-hydroxy-L-prolinamide compound, acts as a proteolysis targeting chimera (PROTAC) [1], specifically inducing degradation of the G12D-mutation KRAS protein.

Rineterkib (ERK-IN-1) is an inhibitor of RAF and ERK1/2 activating mutations in the MAPK pathway.

TH-Z827 is a mutant-selective inhibitor targeting KRAS(G12D) with an IC50 of 2.4 μM, demonstrating specificity by not binding to KRAS(WT) or KRAS(G12C). Additionally, it disrupts the KRAS(G12D)-CRAF interaction with an IC50 of 42 μM [1].

TUS-007, a modified CANDDY (Chemical knockdown with Affinity aNd Degradation DYnamics) molecule originally derived from a proteasome inhibitor, scarcely affects proteasome activity. It is a potent, orally active degrader of KRAS G12D/V, effective in cell-free chemical knockdown of KRAS G12D/V. Furthermore, TUS-007 has been shown to suppress tumor growth [1].

Pan-KRAS-IN-2 (compound 6) is a broad-spectrum KRAS inhibitor exhibiting potent activity with IC50 values of ≤10 nM against KRAS wild type and its mutants (G12D, G12C, G12V, G12S, G12A, Q61H), while showing significantly reduced inhibition, with an IC50 ＞10 μM, for the KRAS G13D mutant [1].

TH-Z835 is a selective inhibitor for the KRAS (G12D) mutation, demonstrating an inhibitory concentration (IC50) of 1.6 μM. It effectively hampers both mantGMPPNP/GPPNP and GPPNP/mantGMPPNP exchanges [1].

KRAS G12D inhibitor 15 is a potent inhibitor specifically targeting the KRAS G12D mutation. It holds potential for research into numerous diseases or disorders, including cancer and its metastases[1].

BC-LI-0186 (4-(2,3-dimethyl-5-oxo-4-propan-2-ylpyrazol-1-yl)-N-(2-phenoxyethyl)benzenesulfonamide) is a potent and selective inhibitor of the interaction of Leucyl-tRNA synthetase (LRS) and Ras-related GTP-binding protein D (RagD) with IC50 of 46.11 nM. BC-LI-0186 competitively binds the RagD interaction site of LRS with Kd of 42.1 nM and has no effect on LRS-vps34, LRS-eprs, RagB-RagD association, mTORC1 complex formation. BC-LI-0186 potently inhibits the activity of tumor-associated MTOR mutants and the growth of rapamycin-resistant cancer cells. BC-LI-0186 can be used for lung cancer-related research.

SAH-SOS1A TFA is a peptide-based SOS1/KRAS protein interaction inhibitor. SAH-SOS1A TFA binds to wild-type and mutant KRAS (G12D, G12V, G12C, G12S, and Q61H) with nanomolar affinity ( EC 50 =106-175 nM). SAH-SOS1A TFA directly and independently blocks nucleotide association. SAH-SOS1A TFA impairs KRAS-driven cancer cell viability and exerts its effects by on-mechanism blockade of the ERK-MAPK phosphosignaling cascade downstream of KRAS [1] .