h358

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

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.

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

HRX-0233 is a small molecule inhibitor targeting MAP2K4. In vivo, HRX-0233 effectively reduces tumors in H358 KRASG12C mutant non-small cell lung cancer (NSCLC) without significant toxicity. This compound also prevents feedback activation of receptor tyrosine kinases (RTKs) when used as a monotherapy with the KRAS inhibitor Sotorasib, leading to more sustained and comprehensive inhibition of the MAPK signaling pathway. HRX-0233 holds potential for research in AR-negative prostate cancer, lung cancer, and colon cancer.

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 inhibitor-37 (compound 2) is a potent inhibitor of KRAS, exhibiting low dissociation constants (KD) with various KRAS mutations: wild type (0.004 nM), G12D (0.041 nM), G12C (0.019 nM), and G12V (0.144 nM). This compound effectively inhibits cell proliferation, demonstrating half-maximal inhibitory concentrations (IC50) ranging from <2 nM to 14 nM in H358, SW620, and PANC08.13 cell lines. KRAS inhibitor-37 holds potential for cancer research applications.

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.

YN14-H is a PROTAC degrader that targets KRASG12C. It effectively inhibits the growth of NCI-H358 and MIA PaCa-2 cells, with IC50 values of 0.042 μM and 0.021 μM, respectively, and DC50 values of 28.9 nM and 18.1 nM. YN14-H significantly induces apoptosis and suppresses cell migration. It demonstrates favorable pharmacokinetics and excellent in vivo antitumor activity.

VVD-699 is a covalent inhibitor of RAS-PI3K. It forms a covalent bond with cysteine at position 242 within the RAS-binding domain of PI3Kp110α, thereby obstructing the ability of RAS to activate PI3K. VVD-699 is capable of inhibiting the growth of tumors with RAS mutations and HER2 overexpression. It is applicable in research related to RAS mutation-associated cancers, such as those involving H358 lung cancer cells, A549 cells, and FaDu 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.

BQU57 selectively inhibits Ral over Ras or Rho and suppresses xenograft tumor growth.

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].

RAF-IN-1 is a potent inhibitor of b cRAF, acting on cRAF (IC50: 3.8 nM), bRAFwt (IC50: 36 nM), and bRAFV600E (IC50: 29.4 nM), and inhibiting A375 and H358 cell lines carrying the bRAFV600E mutation with a GI50 of 3.4 and 2.9 nM, respectively.

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.

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.

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.

KRAS G12C Inhibitor 48 is a potent inhibitor targeting the KRAS G12C mutation, exhibiting an IC50 value of 639.91 nM. Demonstrating antiproliferative activity, KRAS G12C Inhibitor 48 (0-50 µM) yields IC50 values of 0.796 µM, 6.33 µM, and 16.14 µM against H358, H23, and A549 cell lines, respectively.