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MRTX849 

Cat. No.: HY-130149 Purity: 99.72%
Handling Instructions

MRTX849 is a potent, orally-available, and mutation-selective covalent inhibitor of KRAS G12C with potential antineoplastic activity. MRTX849 covalently binds to KRAS G12C at the cysteine at residue 12, locks the protein in its inactive GDP-bound conformation, and inhibits KRAS-dependent signal transduction.

For research use only. We do not sell to patients.

MRTX849 Chemical Structure

MRTX849 Chemical Structure

CAS No. : 2326521-71-3

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Description

MRTX849 is a potent, orally-available, and mutation-selective covalent inhibitor of KRAS G12C with potential antineoplastic activity. MRTX849 covalently binds to KRAS G12C at the cysteine at residue 12, locks the protein in its inactive GDP-bound conformation, and inhibits KRAS-dependent signal transduction[1][2].

IC50 & Target

KRas G12C

 

In Vitro

MRTX849 (0.1-10000 nM; 3-day/2D conditions; 12-day/3D conditions) potently inhibits cell growth in the vast majority of KRAS G12C-mutant cell lines with IC50s ranging between 10 and 973 nM in the 2D format and between 0.2 and 1042 nM in the 3D format[1].
MRTX849 (0.24-1000 nM; 24 hours) inhibits KRAS-dependent signaling targets including ERK1/2 phosphorylation (Thr202/Tyr204 ERK1; pERK), S6 phosphorylation (RSK-dependent Ser235/236; pS6) and expression of the ERK-regulated DUSP6[1].

Cell Viability Assay[1]

Cell Line: MIA PaCa-2, H1373, H358, H2122, SW1573, H2030, KYSE-410 cells (G12C); H1299 (WT); A549 (G12S), HCT116 (G13D) cells
Concentration: 0.1, 1, 10, 100, 1000, 10000 nM
Incubation Time: 24 hours
Result: Inhibits cell growth in the vast majority of KRAS G12C-mutant cell lines with IC50 values ranging between 10 and 973 nM in the 2D format and between 0.2 and 1042 nM in the 3D format.

Western Blot Analysis[1]

Cell Line: MIA PaCa-2 cells
Concentration: 0.24, 0.5, 1.0, 2.0, 3.9, 7.8, 15.6, 31.3, 62.5, 125, 250, 500, 1000 nM
Incubation Time: 24 hours
Result: Inhibits KRAS-dependent signaling targets including ERK1/2 phosphorylation (Thr202/Tyr204 ERK1; pERK), S6 phosphorylation (RSK-dependent Ser235/236; pS6) and expression of the ERK-regulated DUSP6, each with IC50s in the single-digit nanomolar range in cell lines.
In Vivo

MRTX849 (1-100 mg/kg; i.g.; daily until day 16) demonstrates dose-dependent anti-tumor efficacy over a well-tolerated dose range, and the maximally efficacious dose of MRTX849 is between 30-100 mg/kg/day[1].

Animal Model: MIA PaCa-2 model (6-8-week-old, female, athymic nude-Foxn1 nu mice)[1]
Dosage: 1, 3, 10, 30 and 100 mg/kg
Administration: Oral gavage; daily until Day 16
Result: Rapid tumor regression was observed at the earliest posttreatment tumor measurement and animals in the 30 and 100 mg/kg cohorts exhibited evidence of a complete response at study Day 15. Dosing was stopped at study Day 16 and all 4 mice in the 100 mg/kg cohort and 2 out of 7 mice in the 30 mg/kg cohort remained tumor-free through study Day 70.
Clinical Trial
Molecular Weight

604.12

Formula

C₃₂H₃₅ClFN₇O₂

CAS No.

2326521-71-3

SMILES

N#CC[[email protected]@H]1N(C(C(F)=C)=O)CCN(C2=C3C(CN(C4=C5C(Cl)=CC=CC5=CC=C4)CC3)=NC(OC[[email protected]]6N(C)CCC6)=N2)C1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

-20°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

Solvent & Solubility
In Vitro: 

DMSO : 25 mg/mL (41.38 mM; Need ultrasonic)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.6553 mL 8.2765 mL 16.5530 mL
5 mM 0.3311 mL 1.6553 mL 3.3106 mL
10 mM 0.1655 mL 0.8277 mL 1.6553 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (4.14 mM); Clear solution

  • 2.

    Add each solvent one by one:  10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (4.14 mM); Clear solution

*All of the co-solvents are provided by MCE.
References

Purity: 99.72%

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Keywords:

MRTX849MRTX 849MRTX-849RasKRASG12Cselectivecovalentanti-tumorGDP-boundstateinactiveMIA PaCa-2H1373cellsmutantInhibitorinhibitorinhibit

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MRTX849
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