adagrasib  (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: bioRxiv

Article Title: FLIP is essential for oncogenic KRAS- driven lung cancer

doi: 10.64898/2026.08.04.738686

Figure Lengend Snippet: ( A ) Expression of FLIP mRNA (relative to 18S) in KPF1 cells following treatment with KRAS inhibitor MRTX1133 (300nM) or DMSO control for 3, 6 and 24 hours. Significance was tested using one-way ANOVA and adjusted for multiple comparisons with Dunnetts correction. ( B ) Western blot analysis of FLIP L , FLIP R , pERK1/2, ERK1/2, pAkt, Akt, pS6, S6, p43/p18-caspase-8, caspase-3, KRAS and β-actin in KPF1 cells following treatment with 300nM MRTX113 for 3, 6 and 24 hours. The activity of caspase-8 ( C ) and caspase-3/7 ( D ) was analysed in extracted protein lysates from cells treated as in (B) using CaspaseGlo® activity assays (n=3). ( E ) Expression of FLIP mRNA (relative to 18S) in KPF2 cells following treatment as in ( E ) (n=3). Significance was tested using one-way ANOVA and adjusted for multiple comparisons with Dunnetts correction. (* p < 0.05, ns – non-significant). ( F) Western blot analysis of FLIP L , FLIP R , pERK1/2, ERK1/2, pAkt, Akt, pS6, S6, p43/p18-caspase-8, caspase-3, KRAS and β-actin in KPF2 cells following treatment with 300nM MRTX113, 1µM ERK inhibitor (LY3214996), S6K inhibitor (PF4708671) or DMSO (ctrl) for 24 hours. ( G ) Annexin V/PI analysis in KPF1 cells transfected with control (SCR) and Casp8 siRNA for 24 hours prior to treatment with 300nM KRAS i (MRTX1133) for a further 24 hours. Statistical tests were performed using two-way ANOVA and adjusted for multiple comparisons with Bonferroni correction. ( H ) Caspase-3/7 activity was analysed in extracted protein lysates from cells treated as in ( E ) using CaspaseGlo® activity assays, (n=3). ( I ) Annexin V/PI analysis of KPF1 cells pretreated with KRAS i MRTX1133 (300nM) for 24 hours prior to the addition of mTRAIL (25ng/mL) or TNFα (40ng/mL) for a further 24 hours. Statistical tests were performed using two-way ANOVA and adjusted for multiple comparisons with Bonferroni correction. Data are mean +/- SEM.

Article Snippet: Recombinant Mouse TRAIL (TNFSF10 Protein) TNFα were purchased from BioTechne, Emricasan, AZD5991 and LY3214996 from Selleckchem (Waltham Abbey, UK), MRTX1133 from MedChemExpress (NJ, USA) and PF-4708671 from Sigma (Dorset, UK).

Techniques: Expressing, Control, Western Blot, Activity Assay, Transfection

Journal: bioRxiv

Article Title: FLIP is essential for oncogenic KRAS- driven lung cancer

doi: 10.64898/2026.08.04.738686

Figure Lengend Snippet: ( A ) Expression of FLIP mRNA (relative to 18S) in KPF2 cells following treatment with KRAS i MRTX1133 (300nM) or DMSO control for 3, 6 and 24 hours (n=3). Significance was tested using one-way ANOVA and adjusted for multiple comparisons with Dunnetts correction. ( B ) Western blot analysis of FLIP L , FLIP R , pERK1/2, ERK1/2, pAkt, Akt, pS6, S6, p43/p18-caspase-8, caspase-3, KRAS and β-actin in KPF2 cells following treatment with 300nM of KRAS i MRTX113 for 3, 6 and 24 hours. The activity of caspase-8 ( C ) and caspase-3/7 ( D ) was analysed in extracted protein lysates from treated as in ( B ) using CaspaseGlo® activity assays (n=3). Results were compared using Students t -test. ( E ) Western blot analysis of FLIP L , FLIP R , p43/p18-caspase-8, caspase-3 and β-actin in KPF1 cells following treatment as in . ( F ) Annexin V/PI analysis in Cflar WT (KPF1 and KPF2) and null (KPF3 and KPF4) cells following treatment with 300nM KRAS i (MRTX1133) for 24 hours (n=3). Data is shown as fold change relative to control for each cell line. Data are mean +/- SEM.

Article Snippet: Recombinant Mouse TRAIL (TNFSF10 Protein) TNFα were purchased from BioTechne, Emricasan, AZD5991 and LY3214996 from Selleckchem (Waltham Abbey, UK), MRTX1133 from MedChemExpress (NJ, USA) and PF-4708671 from Sigma (Dorset, UK).

Techniques: Expressing, Control, Western Blot, Activity Assay

Journal: bioRxiv

Article Title: Spatial modulation of RAF by RAF/MEK glue enables full-dose combination with pan-RAF inhibitor and potent RAS-mutant tumor-selective MAPK and growth inhibition

doi: 10.64898/2026.07.24.740654

Figure Lengend Snippet: A, KRAS(Q61K) Tet-On MEFs were treated with or without 300 ng/mL doxycycline for 24 hours followed by treatment with DMSO (control), 200 nM belvarafenib (belva), or increasing concentrations of cobimetinib (cobi) alone or in combination with 200 nM belvarafenib for 1 hour, and cell lysates were immunoblotted for KRAS (i, induced; e, endogenous), pMEK, pERK, MEK, and actin. B, MEFs were treated with DMSO (control) or increasing concentrations of cobimetinib (cobi) alone or in combination with 0.5 µM pan-RAF-D or 0.5 µM BRAF-D for 18 hours, and cell lysates were immunoblotted for BRAF, pMEK, pERK, MEK, and actin. C, KRAS(Q61K) Tet-On MEFs were treated with or without 300 ng/mL doxycycline for 24 hours followed by treatment with DMSO (control), 200 nM belvarafenib (belva), or increasing concentrations of avutometinib (avuto) alone or in combination with 200 nM belvarafenib for 1 hour, and cell lysates were immunoblotted for KRAS (i, induced; e, endogenous), pMEK, pERK, MEK, and actin. D, RAS(WT) and RAS(MUT) cells (MEFs and SK-MEL-2 cells, respectively) were treated with DMSO (control), 200 nM naporafenib (napo), increasing concentrations of trametinib (tram) alone or in combination with 200 nM naporafenib, or increasing concentrations of avutometinib (avuto) alone or in combination with 200 nM naporafenib for 24 hours. Cell lysates were immunoblotted for pMEK, pERK, and MEK. E , Table on the top shows KRAS chronos scores from the DepMap portal for the indicated RAS-dependent (ASPC1 and HPAFII) and RAS-independent (SW1990 and PANC-1) cell lines. The graph on the bottom shows cell growth response to 250 nM belvarafenib (belva), 30 nM avutometinib (avuto), or the combination in the indicated cell lines after 6 days of treatment. Data are represented as mean ± SEM. F , The indicated cell lines were treated with 1µM pan-RAF-D for 18 hours. Cell lysates were immunoblotted with BRAF and MEK. G , Cell growth response to 250 nM belvarafenib (belva), 30 nM avutometinib (avuto), or the combination in SK-MEL-2 parental cells and derived cells resistant to daraxonrasib after 6 days of treatment. The graph on the right shows cell growth response to daraxonrasib in SK-MEL-2 parental and daraxonrasib resistant cells after 6 days of treatment. Data are represented as mean ± SEM. H , SK-MEL-2 parental and daraxonrasib resistant cells were treated with DMSO (control), 200 nM belvarafenib (belva), or increasing concentrations of avutometinib (avuto) alone or in combination with 200 nM belvarafenib for 24 hours, and cell lysates were immunoblotted for pMEK, pERK, and actin. I , Cell growth response to 250 nM belvarafenib (belva), 30 nM avutometinib (avuto), or the combination in ASPC1 parental cells and derived cells resistant to MRTX-1133 after 6 days of treatment. The graph on the right shows cell growth response to MRTX-1133 in ASPC1 parental and MRTX-1133 resistant cells after 6 days of treatment. Data are represented as mean ± SEM. J , ASPC1 parental and MRTX-1133 resistant cells were treated with DMSO (control), 200 nM belvarafenib (belva), or increasing concentrations of avutometinib (avuto) alone or in combination with 200 nM belvarafenib for 24 hours, and cell lysates were immunoblotted for pMEK, pERK, and actin.

Article Snippet: Daraxonrasib (HY-148439) and MRTX-1133 (HY-134813) were obtained from MedchemExpress.

Techniques: Control, Derivative Assay