h358 cells

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.

RBC8 is a specific GTPases RalA RalB inhibitor by inhibiting the binding of Ral to its effector RALBP1, no inhibition on the GTPases RhoA and Ras.

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

RMC-6291 is an orally active, covalent inhibitor of KRAS G12C (ON) that forms a tri-complex within tumor cells between KRAS G12C (ON) and cyclophilin A (CypA), thereby preventing KRAS G12C (ON) from signaling via steric blockade of RAS effector binding and eliciting deep and durable suppression of RAS pathway activity in KRAS G12C tumor models [1].

MRTX-1257 is a selective, irreversible, and covalent inhibitor of KRAS G12C with an IC50 of 900 pM for KRAS-dependent ERK phosphorylation in H358 cells. MRTX-1257 demonstrated 31% bioavailability in the mouse, with free fraction exposures well above cellular potency, and 77% target engagement in a PK PD experiment.

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 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.

SOS1-IN-18 (Compound 8) is an inhibitor of the Son of Sevenless 1 protein (SOS1) with a dissociation constant (KD) of 2.6 nM. It disrupts the SOS1-KRAS G12C interaction with an IC50 of 3.4 nM, inhibits ERK phosphorylation in H358 cells with an IC50 of 31 nM, and curtails the proliferation of H358 cells with an IC50 of 5 nM.

RAS RAS-RAF-IN-1 is a potent inhibitor of RAS and RAS-RAF, exhibiting a KD of 5.0 μμ-15 μμ for cyclophilin A (CYPA) binding affinity and demonstrating antitumor activity[1].

SHR902275 is a selective, potent, orally active RAF inhibitor targeting RAS mutant cancers, acting on cRAF (IC50: 1.6 nM), bRAFwt (IC50: 10 nM), and bRAFV600E (IC50: 5.7 nM). SHR902275 exhibits cell growth inhibitory effects in H358 cells (GI50: 1.5 nM), A375 cells (GI50: 0.17 nM), Calu6 cells (GI50: 0.4 nM), and SK-MEL2 cells (GI50: 0.32 nM).

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.

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).

KRAS G12C inhibitor 44 is a potent, orally active KRAS G12C inhibitor. KRAS G12C inhibitor 44 exhibits anti-proliferative effects in MIA PaCA-2 (IC50: 0.016 μM), H358 cells (IC50: 0.028 μM). inhibitor 44 has anti-tumour activity in vivo.

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.

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].

KRAS inhibitor-9 (DUN09716) is a potent KRAS inhibitor with Kd of 92 μM that blocks the formation of GTP-KRAS and downstream activation of KRAS. KRAS inhibitor-9 causes G2 M cell cycle arrest and induces apoptosis. KRAS inhibitor-9 selectively inhibits the proliferation of NSC-LC cells with KRAS mutation but not normal lung cells