nci-h358

Alisertib (MLN 8237) is a specific Aurora A inhibitor (IC50: 1.2 nM). The selectivity of Alisertib(MLN 8237) is >200-fold higher for Aurora A than Aurora B.

Telaglenastat (CB 839) (IC50 of 24 nM), an effective, specific, and oral inhibitor, which is bioavailable glutaminase, for recombinant human GAC.

NVP-231 is a potent, specific and reversible CerK inhibitor(IC50=12±2 nM) that competitively inhibits ceramide binding to CerK.

KRASG12C IN-14 (compound 15), a potent inhibitor specifically designed for the KRAS G12C mutation, exhibits impressive efficacy in impeding CYPA-dependent KRAS-BRAF interaction and ERK phosphorylation in NCI-H358 cells, both with an IC 50 of 0.002 μM.

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 G12C inhibitor 69 (Compound K09) is an inhibitor of the mutant RAS protein KRAS G12C with an IC50 of 4.36 nM. In the cell lines NCI-H358 and MIA-PACA-2, it suppresses ERK phosphorylation with IC50 values of 12 nM and 7 nM, respectively. Additionally, KRAS G12C inhibitor 69 hinders the proliferation of NCI-H358 and MIA-PACA-2 cancer cells, with IC50 values of 3.15 nM and 2.33 nM, respectively.

K20 is a potent and selective inhibitor of KRas G12C (IC50: 1.16 nM). In H358 cells, K20 demonstrates an anticancer effect with an IC50 value of 0.78 μM and inhibits the growth of NCI-H358 tumor cells (TGI: 41%) without significant toxicity. K20 reduces the phosphorylation level of Erk, leading to apoptosis.

BI-0474 is a potent KRASG12C inhibitor that inhibits GDP-KRAS::SOS1 protein-protein interactions with an IC50 value of 7.0 nM.BI-0474 exhibits significant antiproliferative activity against NCI-H358 cells harboring the G12C mutation, and shows significant anti-tumor activity in a non-small cell lung cancer xenograft model. activity.BI-0474 can be used for cancer research.

SHP2-IN-14 (compound 27) is a potent, orally active allosteric inhibitor of SHP2 with an IC50 of 7 nM, exhibiting strong anti-tumor activity, inhibiting tumor progression in NCI-H358 tumor-bearing mice, and demonstrating favorable pharmacokinetic properties and safety [1].

HP661, a selective inhibitor of mitochondrial complex I (NADH dehydrogenase), impedes complex I activity by 77.6% at 1 µM, demonstrating lesser inhibition towards complex III (28.1%) and no inhibitory effects on complexes II and IV. It notably decreases the viability of human lung cancer cells—H460, NCI H441, and trametinib-resistant A549 cells (IC50s = 10.6, 29.7, and 15.1 nM, respectively)—which exhibit high levels of oxidative phosphorylation. In contrast, it shows minimal activity against NCI H358 lung cancer cells and non-cancerous HPNE and MRC-5 cells (IC50s = >10,000 nM for both), which have lower oxidative phosphorylation levels. Furthermore, in an H460 mouse xenograft model, HP661 at a dose of 30 mg/kg twice daily significantly reduces tumor volume and enhances the tumor-growth inhibitory effects of trametinib.

PROTAC SOS1 degrader-5 (compound 4) serves as an effective degrader of PROTAC SOS1, exhibiting a DC50 of 13 nM. It robustly suppresses the proliferation of NCI-H358 cells, with an IC50 value of 5 nM [1].