krasg12d inhibitor mrtx 1133  (MedChemExpress)

Journal: Oncology Letters

Article Title: KRAS (G12D)-selective inhibitor MRTX1133 suppresses proliferation and differentially modulates chemosensitivity in ovarian mucinous carcinoma

doi: 10.3892/ol.2026.15594

Figure Lengend Snippet: MRTX1133 inhibits ERK phosphorylation in KRAS (G12D)-mutant MCAS cells. MCAS cells were incubated with MRTX1133 at 0–100 nM for 3 h in DMEM/F12 containing 10% FBS. Protein lysates were prepared using NP-40 lysis buffer and subjected to SDS-PAGE. ERK phosphorylation was detected by western blotting using anti-phospho-ERK and anti-ERK antibodies, followed by HRP-conjugated secondary antibodies. The levels of phosphorylated ERK were normalized to total ERK. α-actin was used as a loading control. MRTX1133 reduced ERK phosphorylation in a concentration-dependent manner.

Article Snippet: MCAS cells were seeded onto six-well plates at 2×10 5 cells/well, incubated at 37°C for 24 h, then cultured in medium containing 10% FBS with 0–100 nM MRTX1133 (TargetMol Chemicals, Inc.) at 37°C for 3 h. Cells were lysed using lysis buffer (1% NP-40, 150 mM NaCl and 50 mM Tris-HCl; pH 8.0).

Techniques: Phospho-proteomics, Mutagenesis, Incubation, Lysis, SDS Page, Western Blot, Control, Concentration Assay

Journal: Oncology Letters

Article Title: KRAS (G12D)-selective inhibitor MRTX1133 suppresses proliferation and differentially modulates chemosensitivity in ovarian mucinous carcinoma

doi: 10.3892/ol.2026.15594

Figure Lengend Snippet: Selective proliferation inhibition of KRAS (G12D)-mutant MCAS cells by MRTX1133. (A) MCAS, (B) OVKATE, (C) TU-OS-4 and (D) SHIN-3 cells were seeded at 500 cells/well in 96-well plates and treated with 10–400 nM MRTX1133 for 72 h. Cell viability was measured using a water soluble tetrazolium salt-1 colorimetric assay and normalized to untreated controls. The IC 50 was determined as the drug concentration required to reduce cell viability by 50%. MRTX1133 reduced the viability of MCAS cells, with an IC 50 of 37.9±5.9 nM, whereas no IC 50 was reached for OVKATE, TU-OS-4 or SHIN-3 cells within the tested concentration range. Data are presented as the mean ± SD (n=3).

Article Snippet: MCAS cells were seeded onto six-well plates at 2×10 5 cells/well, incubated at 37°C for 24 h, then cultured in medium containing 10% FBS with 0–100 nM MRTX1133 (TargetMol Chemicals, Inc.) at 37°C for 3 h. Cells were lysed using lysis buffer (1% NP-40, 150 mM NaCl and 50 mM Tris-HCl; pH 8.0).

Techniques: Inhibition, Mutagenesis, Colorimetric Assay, Concentration Assay

Journal: Oncology Letters

Article Title: KRAS (G12D)-selective inhibitor MRTX1133 suppresses proliferation and differentially modulates chemosensitivity in ovarian mucinous carcinoma

doi: 10.3892/ol.2026.15594

Figure Lengend Snippet: MRTX1133 differentially modulates chemosensitivity in MCAS cells. MCAS cells were incubated with (A) PTX (4–128 nM), (B) SN38 (0.05–1.6 µM), (C) GEM (1–32 µM) or (D) CDDP (4–128 µM) for 72 h, with or without 100 nM MRTX1133. Viability was measured using a water soluble tetrazolium salt-1 assay and IC 50 was calculated. MRTX1133 significantly increased the IC 50 of cell cycle-dependent drugs (PXT, SN38 and GEM) but not that of CDDP. Data are presented as the mean ± SD (n=3). *P<0.01. n.s., not significant; PTX, pixatel; GEM, gemcitabine; CDDP, cisplatin.

Article Snippet: MCAS cells were seeded onto six-well plates at 2×10 5 cells/well, incubated at 37°C for 24 h, then cultured in medium containing 10% FBS with 0–100 nM MRTX1133 (TargetMol Chemicals, Inc.) at 37°C for 3 h. Cells were lysed using lysis buffer (1% NP-40, 150 mM NaCl and 50 mM Tris-HCl; pH 8.0).

Techniques: Incubation

Journal: Oncology Letters

Article Title: KRAS (G12D)-selective inhibitor MRTX1133 suppresses proliferation and differentially modulates chemosensitivity in ovarian mucinous carcinoma

doi: 10.3892/ol.2026.15594

Figure Lengend Snippet: MRTX1133-mediated proliferation inhibition is not reversed by inhibition of programmed cell death pathways. MCAS cells were pretreated with inhibitors of apoptosis (Z-VAD-FMK, pan-caspase inhibitor), pyroptosis (Z-YVAD-FMK, caspase-1 inhibitor), ferroptosis (ferrostatin-1, lipid peroxidation inhibitor) or necroptosis (necrostatin-1, RIPK1 inhibitor) at 100 µM for 1 h, followed by exposure to 100 nM MRTX1133 for 48 h. Cell viability was measured using a water soluble tetrazolium salt-1 assay. None of the inhibitors restored cell viability. Data are presented as the mean ± SD (n=3). n.s., not significant.

Article Snippet: MCAS cells were seeded onto six-well plates at 2×10 5 cells/well, incubated at 37°C for 24 h, then cultured in medium containing 10% FBS with 0–100 nM MRTX1133 (TargetMol Chemicals, Inc.) at 37°C for 3 h. Cells were lysed using lysis buffer (1% NP-40, 150 mM NaCl and 50 mM Tris-HCl; pH 8.0).

Techniques: Inhibition

Journal: Oncology Letters

Article Title: KRAS (G12D)-selective inhibitor MRTX1133 suppresses proliferation and differentially modulates chemosensitivity in ovarian mucinous carcinoma

doi: 10.3892/ol.2026.15594

Figure Lengend Snippet: MRTX1133 suppresses Ki-67 mRNA expression in MCAS cells. MCAS cells were incubated with 100 nM MRTX1133 for 24 h and Ki-67 mRNA expression was quantified using reverse transcription-quantitative PCR. Total RNA was extracted using the RNeasy Mini Kit, reverse transcribed and amplified using specific primers. Expression levels were normalized to GAPDH. MRTX1133 significantly reduced Ki-67 mRNA levels. Data are presented as the mean ± SD (n=3). *P<0.01.

Article Snippet: MCAS cells were seeded onto six-well plates at 2×10 5 cells/well, incubated at 37°C for 24 h, then cultured in medium containing 10% FBS with 0–100 nM MRTX1133 (TargetMol Chemicals, Inc.) at 37°C for 3 h. Cells were lysed using lysis buffer (1% NP-40, 150 mM NaCl and 50 mM Tris-HCl; pH 8.0).

Techniques: Expressing, Incubation, Reverse Transcription, Real-time Polymerase Chain Reaction, Amplification

Journal: Oncology Letters

Article Title: KRAS (G12D)-selective inhibitor MRTX1133 suppresses proliferation and differentially modulates chemosensitivity in ovarian mucinous carcinoma

doi: 10.3892/ol.2026.15594

Figure Lengend Snippet: MRTX1133 downregulates phase-specific cyclin mRNA expression in MCAS cells. MCAS cells were incubated with 100 nM MRTX1133 for 24 h. Cyclin D1 (G 1 phase), cyclin A2 (S/G 2 phase) and cyclin B1 (G 2 /M phase) mRNA levels were measured using reverse transcription-quantitative PCR with GAPDH normalization. MRTX1133 reduced the mRNA expression of all three cyclins. Data are presented as the mean ± SD (n=3). *P<0.01.

Article Snippet: MCAS cells were seeded onto six-well plates at 2×10 5 cells/well, incubated at 37°C for 24 h, then cultured in medium containing 10% FBS with 0–100 nM MRTX1133 (TargetMol Chemicals, Inc.) at 37°C for 3 h. Cells were lysed using lysis buffer (1% NP-40, 150 mM NaCl and 50 mM Tris-HCl; pH 8.0).

Techniques: Expressing, Incubation, Reverse Transcription, Real-time Polymerase Chain Reaction

Journal: Cancer Discovery

Article Title: Preclinical Characterization and Clinical Activity of RNK08954 , a Highly Selective and Orally Bioavailable KRAS G12D Inhibitor

doi: 10.1158/2159-8290.CD-25-1346

Figure Lengend Snippet: RNK08954 is a potent and selective noncovalent KRAS G12D inhibitor. A, Structure of RNK08954 . B, KD values of RNK08954 for KRAS G12D , KRAS G12C , KRAS G12V , and KRAS WT were determined using inactive/active KRAS (GDP/GCP-loaded) SPR assays. C and D, Western blot assay of KRAS pathway targets p-ERK1/2 in SW1990 cells treated for 6/24/48/72 hours with RNK08954 (seven doses in total). Data are representative of several independent similar experiments; the statistics are shown in D . E, Cytotoxic effects of RNK08954 and MRTX1133 in cancer cell lines with KRAS G12D/C/V/S mutation and cell lines without KRAS mutation, also Ba/F3 cells with the expression of WT HRAS/NRAS/KRAS and corresponding G12D mutation in HRAS/NRAS/KRAS protein. Cell lines were treated with the indicated concentrations of RNK08954 and MRTX1133 for 72 hours. Cell viability was then assessed using CTG. Top concentration: 333.33 mmol/L for human tumor cell lines and 10 μmol/L for Ba/F3 cell lines. F, Scatter plot shows the IC 50 values of RNK08954 and MRTX1133 in KRAS-mutant cell lines.

Article Snippet: MRTX1133 is the first noncovalent, potent, and selective KRAS G12D inhibitor ( , ) although recently, Bristol Myers Squibb has announced termination of the development of MRTX1133 because of the high instability of the PK profile.

Techniques: Western Blot, Mutagenesis, Expressing, Concentration Assay