kras g12d inhibitor 1

KRAS G12D inhibitor 1 (example 243) is an inhibitor of KRAS G12D, exhibiting an IC50 of 0.8 nM for KRAS G12D-mediated ERK phosphorylation [1].

KRAS G12D inhibitor 15 is a potent and specific inhibitor targeting the KRAS G12D mutation, showing potential for research into various diseases and disorders, including cancer and its metastases [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.

KRAS G12D inhibitor 19 (Compound 7) is used in cancer research [1]. As a specific inhibitor of KRAS G12D, it targets and potentially suppresses this mutation, which is frequently associated with various cancers.

KRAS G12D inhibitor 14 is a potent compound that binds the KRAS G12D protein (Kd: 33 nM) and selectively inhibits the active form KRAS G12D-GTP, but not KRAS G13D.

KRAS G12D inhibitor 12 is an effective inhibitor of KRAS G12D. The Ras protein family is an important intracellular signaling molecule, which plays an important role in growth and development. KRAS G12D inhibitor 12 has the potential to perform KRAS G12D-mediated cancer studies.

KRAS G12D inhibitor 11 is a potent inhibitor of KRAS G12D, a key protein in the Ras family involved in crucial intracellular signaling for growth and development. This inhibitor has shown potential for investigating KRAS G12D-mediated cancers [KRAS G12D, Ras family, intracellular signaling, growth, development, cancer].

KRAS G12D inhibitor 13 is a potent inhibitor of KRAS G12D with potential for the investigation of KRAS G12D-mediated cancers.

KRAS G12D Inhibitor 10 is a potent agent targeting the KRAS G12D mutation, a variant in the Ras protein family crucial for cellular growth and development. This compound shows promise for investigating cancers mediated by KRAS G12D.

KRAS G12D Inhibitor 16 is a potent compound targeting the KRAS G12D and its mutation, exhibiting inhibitory activity with IC50 values of 0.7 nM and 0.35 μM, respectively. It is utilized in researching various malignant tumors including pancreatic ductal adenocarcinomas (PDAC), colon and rectal carcinomas (CRC), and non-small cell lung carcinomas (NSCLC).

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

AMG410 is a non-covalent, bimodal GDP (OFF) and GTP (ON)-binding pan-KRAS inhibitor with Kd (GDP) = 1 nM and Kd (GTP) = 22 nM, which enables circulation-independent blockade of KRAS. AMG410 is more than 100-fold selective for KRAS than HRAS and NRAS2, binds on the same variegated pocket as KRAS G12C inhibitors, and has high potency in KRAS G12D, G12V, G12C, G13D and other mutants, IC 50 = 1-4 nM. AMG140 regresses tumors and reduces phosphorylated ERK levels in colorectal, pancreatic and lung models of KRAS mutations.

MEK RAF-IN-1 (Compound 16b) serves as an inhibitor targeting both MEK and RAF, demonstrating potent efficacy with IC 50 values reported at 28 nM for MEK1, and 3 nM for both BRAF and BRAFV600E. This compound exhibits significant antitumor capabilities, effectively curbing cell proliferation in vitro in MIA PaCa-2 (G12C KRAS), HCT116 (G13D KRAS), and C26 (G12D KRAS) cells. Furthermore, MEK RAF-IN-1 significantly restricts tumor growth in xenograft mouse models employed in the study of colorectal cancer.

KRAS G12D inhibitor 25 (Compound 148) acts as an inhibitor for KRAS G12C and HSP90α, displaying IC50 values of <0.1 μM and 0.1-1 μM respectively. Additionally, it suppresses the proliferation of MIA PaCa-2 and NCI-H358 cell lines, with EC50 values of <0.1 μM and 0.1-1 μM correspondingly. This compound also promotes the degradation of ERBB2, exhibiting a DC50 of 0.1-1 μM.

KRAS inhibitor-27 (Compound 15h) is a KRAS inhibitor that effectively targets KRAS G12D G12V mutated cells (AsPC-1 and SW620) and wild-type KRAS cells (HT-29), with IC50 values of 378 nM, 0.6 nM, and 3230 nM, respectively. It reduces ERK phosphorylation, with IC50 values of 0.6 nM and 1 nM in AsPC-1 and SW620 cells, respectively, and decreases DUSP4 expression, thereby inhibiting the MAPK signaling pathway.

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.

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].

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] .

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].

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].

Paluratide (LUNA18) is a reversible cyclic peptide KRAS inhibitor with the advantages of oral availability and cell permeability for the treatment of kras-mutant cancers, which inhibits cancer cell proliferation by phosphorylating ERK and AKT, and also inhibits the interaction of RAS with guanine nucleotide exchange factors (GEFs).

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-Z816 acts as a reversible inhibitor targeting the KRAS(G12D) mutation, exhibiting an IC50 of 14 µM. This compound is utilized in cancer research [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.