KRAS G12D-IN-37
KRAS G12D-IN-37 is a KRASG12D inhibitor. KRAS G12D-IN-37 shows antiproliferative activity against KRASG12D mutant tumor cells and minimal cytotoxicity toward normal cells. KRAS G12D-IN-37 binds stably to KRASG12D via hydrogen bond interactions with residues His 95, Arg 68, and Asp 12, and inhibits downstream ERK/AKT signaling pathways. KRAS G12D-IN-37 elevates ROS levels, induces apoptosis, disrupts mitochondrial membrane potential. KRAS G12D-IN-37 downregulates the level of anti-apoptotic protein Bcl-2, and upregulates the levels of pro-apoptotic proteins Bax and caspase 3. KRAS G12D-IN-37 can be used for the research of cancer, such as gastric adenocarcinoma and colorectal cancer.
For research use only. We do not sell to patients.
- Formula: C29H34F3N5O3
- Molecular Weight:557.61
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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Biological Activity
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KRas G12D |
Bcl-2 |
Bax |
Caspase 3 |
KRAS G12D-IN-37 (Compound 16k) (72 h) potently inhibits the proliferation of KRASG12D-mutant AGS and GP2D cells with IC50 values of 0.18 μM and 0.21 μM, respectively, while showing lower activity against other KRAS mutant cells, KRAS wild-type cells, and normal HIEC cells[1].
KRAS G12D-IN-37 (0.31-2.5 μM; 24-72 h) exhibits time-dependent cytotoxicity against KRASG12D-mutant AGS and GP2D cells[1].
KRAS G12D-IN-37 (0.0625-0.5 μM; 14 days) potently inhibits the colony formation of KRASG12D-mutant AGS and GP2D cells in a dose-dependent manner[1].
KRAS G12D-IN-37 (0.625-2.5 μM; 6 h) inhibits the downstream ERK/AKT signaling pathways of KRAS in KRASG12D-mutant AGS and GP2D cells, reducing p-ERK and p-AKT levels in a dose-dependent manner[1].
KRAS G12D-IN-37 (0.625-2.5 μM; 24 h) dose-dependently enhances intracellular ROS accumulation and disrupts mitochondrial membrane potential in KRASG12D-mutant AGS and GP2D cells[1].
KRAS G12D-IN-37 (0.625-5 μM; 24 h) dose-dependently induces apoptosis in KRASG12D-mutant AGS and GP2D cells, dose-dependently altering the balance of pro- and anti-apoptotic proteins and increasing Caspase 3 activity[1].
KRAS G12D-IN-37 (1 μM) demonstrates favorable metabolic stability in rat liver microsomes, with a half-life of 289 min[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:KRAS G12D-mutant AGS and GP2D cells
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Concentration:0.0625, 0.125, 0.25, 0.5 μM
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Incubation Time:14 days (medium changes every 72 h)
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Result:Dose-dependently inhibited colony formation of AGS and GP2D cells.
Almost entirely suppressed AGS cell colony formation at 0.25 μM; almost entirely suppressed GP2D cell colony formation at 0.5 μM.
Showed superior colony formation inhibition efficacy compared to MRTX 1133 (HY-134813).
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Cell Line:KRAS G12D-mutant AGS and GP2D cells
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Concentration:0.625, 1.25, 2.5 μM
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Incubation Time:6 h
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Result:Decreased the phosphorylation of ERK and AKT in AGS and GP2D cells.
Reduced p-AKT levels by 90% and p-ERK levels by 70% in GP2D cells at 2.5 μM; the effect on p-AKT/AKT was comparable to that of MRTX 1133.
Caused p-ERK levels to rebound at 1.25 μM in GP2D cells, potentially due to negative feedback in RAS signaling.
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Cell Line:KRAS G12D-mutant AGS and GP2D cells
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Concentration:0.625, 1.25, 2.5 μM
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Incubation Time:24 h
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Result:Induced apoptosis in AGS and GP2D cells in a dose-dependent manner.
Induced apoptosis in 80% of AGS cells at 5 μM; induced apoptosis in a high proportion of GP2D cells at 2.5 μM.
Induced higher apoptosis rates than MRTX 1133, with most apoptotic events occurring in the early stage.
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Cell Line:KRAS G12D-mutant AGS and GP2D cells
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Concentration:0.625, 1.25, 2.5 μM
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Incubation Time:24 h
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Result:Dose-dependently upregulated the levels of pro-apoptotic proteins Bax and Caspase 3, and downregulated the level of anti-apoptotic protein Bcl-2 in AGS and GP2D cells.
Dose-dependently increased Caspase 3 activity in both cell lines.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Healthy Kunming mice (equally divided by sex)[1]
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Dosage:1500 mg/kg; 1200 mg/kg; 1000 mg/kg; 500 mg/kg
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Administration:p.o.; single dose
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Result:Caused death of all mice at 1500 mg/kg.
Led to death of 2 of 6 mice at 1200 mg/kg, with a calculated median lethal dose (LD50) of approximately 1270 mg/kg.
Showed no notable weight loss or physical abnormalities in mice treated with 500 mg/kg or 1000 mg/kg over 14 days.
Revealed no significant morphological changes or cellular abnormalities in heart, liver, spleen, lungs, and kidneys of mice treated with 1000 mg/kg.
Chemical Information
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Molecular Weight 557.61
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Formula C29H34F3N5O3
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SMILES
FC(C1=CC=C(OC)C(C2=CC3=NC(OC[C@H]4CCCN4C)=NC(N5C[C@H](N6)CC[C@H]6C5)=C3C=C2OC)=C1)(F)F
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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