k ras in 1

K-Ras-IN-1, a K-Ras inhibitor, is characterized by its chemical formula C20H19ClN4O2S and is also known as N-[(1S)-3-cyclopropyl-1-[(6-fluoro-1H-benzimidazol-2-yl)sulfanyl]-2-oxo-1-(phenylmethyl)propyl]-4-fluorobenzenesulfonamide (compound [18, dashboard 819041] in brackets).

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

K-Ras-PDEδ-IN-1 is a potent inhibitor of competitive K-Ras-PDEδ that binds to the farnesyl binding pocket of PDEδ (Kd of 8 nM).

K-Ras ligand-Linker Conjugate 1 is a chemical compound that includes a ligand for K-Ras and a PROTAC linker, facilitating the recruitment of E3 ligases VHL, CRBN, MDM2, and IAP. It can be utilized in the synthesis of PROTAC K-Ras Degrader-1, a highly effective K-Ras degrader that achieves ≥70% degradation efficacy in SW1573 cells [1].

K-Ras ligand-Linker Conjugate 2 is a chemical compound that includes a ligand for K-Ras and a PROTAC linker, capable of recruiting E3 ligases like VHL, CRBN, MDM2, and IAP. It is utilized in synthesizing PROTAC K-Ras Degrader-1, a highly effective PROTAC K-Ras degrader with a degradation efficacy of ≥70% in SW1573 cells[1].

K-Ras ligand-Linker Conjugate 3 (Compound 001371) is a chemical compound comprising a ligand for the K-Ras recruiting moiety and a PROTAC linker, responsible for recruiting E3 ligases (e.g., VHL, CRBN, MDM2, and IAP). This compound is essential for synthesizing PROTAC K-Ras Degrader-1, a potent degrader with a degradation efficacy of ≥70% in SW1573 cells[1].

K-Ras ligand-Linker Conjugate 4 is a chemical compound combining a K-Ras recruiting ligand with a PROTAC linker, responsible for recruiting E3 ligases such as VHL, CRBN, MDM2, and IAP. It has the potential to be used in synthesizing PROTAC K-Ras Degrader-1, which shows a degradation efficacy of ≥70% in SW1573 cells[1].

K-Ras ligand-Linker Conjugate 5 is a chemical compound combining a K-Ras recruiting ligand with a PROTAC linker for E3 ligases, such as VHL, CRBN, MDM2, and IAP. This conjugate is crucial for synthesizing PROTAC K-Ras Degrader-1, displaying a degradation efficacy of ≥70% in SW1573 cells [1].

THP-PEG4-Pyrrolidine(N-Boc)-CH2OH is a polyethylene glycol (PEG)-based PROteolysis TArgeting Chimera (PROTAC) linker used in synthesizing PROTAC K-Ras Degrader-1, as documented in reference [1].

THP-PEG4-Pyrrolidine(N-Me)-CH2OH, a PEG-based PROTAC linker, aids in the synthesis of PROTAC K-Ras Degrader-1[1].

Tos-PEG4-THP is a polyethylene glycol (PEG) derivative utilized as a linker in the synthesis of PROTAC K-Ras Degrader-1, a potential therapeutic compound for targeted degradation of K-Ras protein [1].

XMU-MP-9, a bifunctional compound, targets the C2 domain of Nedd4-1 and the allosteric site of K-Ras. It enhances the interaction and induces conformational changes within the Nedd4-1/K-Ras complex. Furthermore, XMU-MP-9 facilitates the ubiquitination and degradation of various K-Ras mutants and inhibits the proliferation of cells with these mutants. This compound is useful in cancer research.

PROTAC K-Ras Degrader-3 is a PROTAC degrader targeting K-Ras, exhibiting a DC50 value of ≤ 1 nM against SW620 KRAS G12D and a GI50 value of ≤ 10 nM in inhibiting the growth of SW620 3D cells. It is used in cancer research.

PROTAC K-Ras Degrader-4 (Compound 4) is a proteolysis-targeting chimera (PROTAC) molecule designed to selectively degrade oncogenic mutants of K-Ras, effectively degrading KRASG12D in the GP5d cell line and KRASG12V in SW620 cells with DC50 of 1 nM and 13 nM, respectively; it concomitantly inhibits the downstream MAPK signaling pathway and represents a novel therapeutic strategy for cancer research targeting previously undruggable Ras mutations.

K-Rasligand-Linker Conjugate 6 formate includes a target protein K-Ras ligand (K-Ras recruitment motif) and a PROTAC linker, capable of recruiting E3 ligases such as VHL, CRBN, MDM2, and IAP. It is utilized in synthesizing PROTACK-Ras Degrader-1, a potent PROTACK-Ras degrader, achieving a K-Ras degradation rate of ≥70% in SW1573.

Spiro-oxanthromicin A is a polyketide that has been found inStreptomyces.1It induces mislocalization of K-RAS in MDCK cells (IC50= 26.7 μM). 1.Salim, A.A., Xiao, X., Cho, K.J., et al.Rare Streptomyces sp. polyketides as modulators of K-Ras localisationOrg. Biomol. Chem.12(27)4872-4878(2014)

CP-609754 (LNK-754) is a potent and reversible farnesyltransferase inhibitor with potential anticancer activity. It inhibits farnesylation of recombinant human H-Ras (IC50=0.57 ng/mL) and K-Ras (IC50=46 ng/mL)[1]. In 3T3 H-ras (61L)-transfected cell lines, CP-609754 exhibits a slow on/off rate, inhibiting mutant H-Ras farnesylation with an IC50 of 1.72 ng/mL[1]. The compound is competitive for the prenyl acceptor (H-Ras protein) and noncompetitive for the prenyl donor farnesyl PPI, selectively inhibiting farnesylation of both H- and K-Ras proteins in 3T3 transfectants[1]. In vivo, CP-609754 shows antitumor activity against 3T3 H-ras (61L) tumors, with tumor regression achieved at 100 mg/kg twice daily and an ED50 for tumor growth inhibition at 28 mg/kg[1]. Continuous i.p. infusion of CP-609754 inhibits tumor growth by over 50% and reduces tumor farnesyltransferase activity by over 30% when plasma concentration is maintained above 118 ng/mL[1]. [1]. Stacy L Moulder, et al. A phase I open label study of the farnesyltransferase inhibitor CP-609,754 in patients with advanced malignant tumors. Clin Cancer Res. 2004 Nov 1;10(21):7127-35.

GGTI-286 is a potent, cell permeable GGTase I inhibitor (IC50: 2 μM). GGTI-286 inhibits Rap1A geranylation in NIH3T3 cells (IC50: 2 μM) more potently than H-Ras farnesylation (IC50>30 μM). Ras4B stimulation (IC50: 1 μM).

GGTI-286 hydrochloride is a potent inhibitor of GGTase I (IC50: 2 μM) and is also effective in inhibiting K-Ras4B (IC50: 1 μM). farnesylation (IC50=2 and >30 μM).

GGTI-286 TFA is a potent, cell-permeable inhibitor of GGTase I, exhibiting 25 times greater effectiveness (IC 50 = 2 μM) compared to the corresponding methyl ester of FTI-276. It specifically targets the geranylgeranylation of Rap1A, demonstrating significant selectivity over the farnesylation of H-Ras in NIH3T3 cells (IC 50s = 2 and >30 μM, respectively). Additionally, GGTI-286 TFA effectively inhibits the stimulation of oncogenic K-Ras4B with an IC 50 of 1 μM.

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].

KRpep-2d, a potent inhibitor of K-Ras, effectively suppresses the proliferation of cancer cells driven by K-Ras. This compound is suitable for use in cancer research [1].

RORγ antagonist 1 (compound 22), a potent derivative of betulinic acid, acts as an antagonist to RORγ with a dissociation constant (K D) of 0.18 μM. It demonstrates anti-proliferative effects in the HPAF-II pancreatic cancer xenograft model, inhibits the RAS/MAPK and AKT/mTORC1 signaling pathways, and triggers caspase-dependent apoptosis in pancreatic cancer cells [1].

ICMT-IN-7 (compound 74), with an IC50 value of 0.015 µM, functions as an ICMT inhibitor, promotes cytoplasmic accumulation of ICMT in HCT-116 cells in a dose-dependent manner and suppresses the proliferation of various cancer cell lines harboring K-Ras and N-Ras mutations [1].