KRas G12C inhibitor 1 is a compound that inhibits KRas G12C.

PROTAC KRAS G12C degrader-1, a cereblon-based degrader, promotes CRBN/KRAS G12C dimerization and facilitates the degradation of GFP-KRAS G12C in reporter cells [1].

KRAS mutant protein inhibitor 1 is a KRAS mutant protein inhibitor for potential treatment in cancer.

KRAS G12C mutant protein inhibitor A-1 can be used in studies about Ras.

KRAS G12D modulator-1 (compound 6), a potent modulator of KRAS G12D, exhibits IC50 values ranging from 1-10 μM against NEA-G12D, PPI-G12D, and p ERK-AGS, and is utilized in cancer research [1].

KRas G12R Inhibitor 1 (compound 3) is a selective covalent inhibitor targeting the KRas G12R mutation, leveraging the high nucleophilicity of mutant cysteines to bind irreversibly within the K-Ras Switch II region. This compound is utilized in cancer research [1].

SOS1/KRAS-IN-1 (Compound 2) serves as an inhibitor of SOS1/KRAS, with potential application in the study of diseases mediated by SOS1/KRAS [1].

KRAS degrader-1 (compound 1) is a potent agent that selectively targets KRAS proteins for destruction via the autophagy-lysosomal degradation pathway [1].

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].

DCLK1-IN-1 is a selective and in vivo-compatible chemical probe of the DCLK1 kinase domain .

BI-3406 is an orally active, highly potent and selective between KRAS and Son of Sevenless 1 (SOS1) interaction inhibitor(IC50 : 6 nM),with anticancer activity.

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.

PROTAC SOS1 degrader-1, a potent compound, demonstrates an effective degradation of PROTAC SOS1 with a DC50 value of 98.4 nM. It exhibits antiproliferative activity against cancer cells harboring diverse KRAS mutations and has shown an antitumor effect with low toxicity [1].

GAGGVGKSAL, a wild-type KRAS G12D 10mer peptide, serves as an immunogenic neoantigen in cancer immunotherapy research [1].

GADGVGKSA, a mutant KRAS G12D 9mer peptide, serves as an immunogenic neoantigen for cancer immunotherapy research [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.

GADGVGKSAL, a mutant KRAS G12D 10mer peptide, serves as an immunogenic neoantigen in cancer immunotherapy research [1].

PROTAC K-Ras Degrader-1 is potent degrader of K-Ras based PROTAC.

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].

RMC-4998 is a molecular glue compound exhibiting potent antitumor activity, capable of forming a ternary complex with CYPA and an activated KRAS G12C mutation. Binding of CYPA to KRAS G12C impedes the interaction between activated KRAS mutants and downstream effector proteins, thus obstructing proliferative cell signaling [1].

GAGGVGKSA, a wild-type KRAS G12D 9mer peptide, serves as an immunogenic neoantigen pivotal for cancer immunotherapy research [1].

GDC-0623 (RG 7421) is a potent and ATP-uncompetitive MEK1 inhibitor with Ki of 0.13 nM. Phase 1.

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

PROTAC KRAS G12C Degrader-3 (Comp 283) serves as a potent degrader of KRAS G12C, utilized in cancer research [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].

SHP2-IN-22, a potent SHP2 allosteric inhibitor, exhibits an IC50 value of 17.7 nM and effectively suppresses proliferation, migration, and invasion in MIA PaCa-2 pancreatic cancer cells. This compound is utilized in the study of Kirsten rat sarcoma viral oncogene (KRAS) mutant cancer research [1].

LJI308 is a potent, and pan-RSK (p90 ribosomal S6 kinase) inhibitor with IC50 of 6 nM, 4 nM, and 13 nM for RSK1, RSK2, and RSK3, respectively.

(S)-JDQ-443 is an isomer of JDQ-443 . JDQ-443 is an orally active, potent, selective, and covalent KRAS G12C inhibitor. JDQ-443 shows antitumor activity [1] [2] .

KRAS inhibitor-11 is a KRAS inhibitor .

KRAS G12C inhibitor 43 is a potent inhibitor of KRAS G12C and inhibits the migration and proliferation of H358 cells (IC50: 0.001-1 μM μM), A549 cells (IC50>1 μM) and HCC cells (IC50>1 μM).

FGTI-2734 mesylate, a RAS C-terminal mimetic compound with dual farnesyl transferase (FT) and geranylgeranyl transferase-1 (GGT) inhibitory activities (IC50s of 250 nM and 520 nM for FT and GGT, respectively), mitigates KRAS resistance by preventing its membrane localization, effectively impeding mutant KRAS patient-derived pancreatic tumors.

AMG-47a is a potent inhibitor of Lck and T cell proliferation. AMG-47a could promote the degradation of the KRAS oncoprotein. AMG-47a selectively reduced the levels of EGFP-KRASG12V protein but did not affect EGFP protein in cells.

NG 25 is a type II kinase inhibitor that inhibits MAP4K2 and TAK1 (IC50s = 21.7 and 149 nM, respectively).1It also inhibits the Src family kinases Src and LYN (IC50s = 113 and 12.9 nM, respectively) and Abl family kinases (IC50s = 75.2 nM), as well as CSK, FER, and p38α (IC50s = 56.4, 82.3, and 102 nM, respectively). NG 25 (100 nM) prevents TNF-α-induced IKKα/β phosphorylation and IκB-α degradation in L929 cells. It inhibits secretion of IFN-α and IFN-β induced by CpG type B and CL097, respectively, in Gen2.2 cells in a concentration-dependent manner.2NG 25 decreases cell viability of HCT116KRASWT, and to a greater degree of HCT116KRASG13D, colorectal cancer cells in a concentration-dependent manner.3It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26KRASG12Dmouse orthotopic model of colorectal cancer. 1.Tan, L., Nomanbhoy, T., Gurbani, D., et al.Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2)J. Med. Chem.58(1)183-196(2015) 2.Pauls, E., Shpiro, N., Peggie, M., et al.Essential role for IKKβ in production of type 1 interferons by plasmacytoid dendritic cellsJ. Biol. Chem. 287(23)19216-19228(2012) 3.Ma, Q., Gu, L., Liao, S., et al.NG25, a novel inhibitor of TAK1, suppresses KRAS-mutant colorectal cancer growth in vitro and in vivoApoptosis24(1-2)83-94(2019)

KRAS inhibitor-12 (compound 6-1) is a potent inhibitor of KRAS G12C (IC50: 0.537 μM). KRAS inhibitor-12 exhibits p-ERK inhibition in MIA PaCA-2, A549 cells with IC50 values of 1.3, 3.7 μM respectively. KRAS inhibitor-12 has potential to be studied in pancreatic, colorectal and lung cancers.

K-Ras G12C-IN-1 is a novel and irreversible inhibitor of mutant K-ras G12C.

KRASG12C IN-2 (compound 17) is an orally active inhibitor of KRAS G12C, which effectively suppresses tumor growth in mice [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] .

KRas/son of sevenless 1 (SOS1) interaction inhibitor. Binds within nucleotide binding pocket of KRas (Kd values are 106 - 176 nM for wild type KRas and various KRas mutants). Inhibits nucleotide binding to KRas in a concentration dependent manner. Display

KRAS G12C inhibitor 61 (Example 3) demonstrates potent activity by inhibiting phospho-ERK 1/2 in MIA PaCa-2 cells, reflected in an IC50 value of 9 nM. This inhibitor is applicable in the research of pancreatic, colorectal, and lung cancers [1].

KRAS inhibitor-10 (WO2021005165 A1, compound 11) is a potent and selective inhibitor of RAS proteins, with a specific focus on KRAS proteins. This orally active anti-cancer agent demonstrates strong efficacy in cancer research, specifically in pancreatic cancer, breast cancer, multiple myeloma, leukemia, and lung cancer. KRAS inhibitor-10 is classified as a tetrahydroisoquinoline compound. Its inhibitory properties provide valuable insights and potential therapeutic applications in the field of oncology [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].

Deltasonamide 1 TFA functions as a PDE6δ-KRas inhibitor, exhibiting a dissociation constant (K_D) of 203 pM, indicating its high affinity for this target. It is utilized in tumor research [1].

FGTI-2734 is a dual farnesyl transferase (FT) and geranylgeranyl transferase-1 (GGT-1) inhibitor, exhibiting IC50 values of 250 nM and 520 nM for FT and GGT-1, respectively. It effectively prevents the membrane localization of KRAS, addressing the issue of KRAS resistance and inhibiting the growth of mutant KRAS patient-derived pancreatic tumors.

SCH772984 HCl is a selective inhibitor of ERK1/2 that displays behaviors of both type I and type II kinase inhibitors, with IC50s of 4 and 1 nM, respectively. SCH772984 HCl has nanomolar cellular potency in tumor cells with mutations in BRAF, NRAS, or KRA

RAS/RAS-RAF-IN-1 is a potent RAS and RAS-RAF inhibitor. RAS/RAS-RAF-IN-1 has a KD of 5.0 μμ-15 μμ for cyclophilin A (CYPA) binding affinity. RAS/RAS-RAF-IN-1 has antitumor activity[1]. RAS/RAS-RAF-IN-1 (compound 89; for 4 hours) has an EC50 of 0.5 μμ-5.0 μμ for BRAF-GTP-KRAS-G12C disruption and has an IC50 of 1.0 μμ-10 μμ for pERK inhibition in H358 cells[1]. [1]. Meizhong Jin, et al. Compounds that participate in cooperative binding and uses thereof. WO2020132597A1.

Pan-KRAS-IN-3 (Example 84) is a pan-KRAS inhibitor suitable for cancer research [1].

Pan-KRAS-IN-4 (compound 5) is a potent KRAS inhibitor, demonstrating IC50 values of 0.37 nM for Kras G12C and 0.19 nM for Kras G12V [1].

KRAS G12C Inhibitor 60 (compound 23), a selective inhibitor targeting the Kras-G12C mutation, is utilized in the investigation of lung, colorectal, and pancreatic cancers [1].

KRAS G12C inhibitor 45 is a potent KRAS G12C inhibitor .