2. GPCR/G Protein MAPK/ERK Pathway
  3. Ras
  4. MRTX1133

MRTX1133 is a noncovalent, potent, and selective KRAS G12D inhibitor. MRTX1133 optimally fills the switch II pocket and extends three substituents to favorably interact with the protein, resulting in an estimated KD against KRAS G12D of 0.2 pM. MRTX1133 prevents SOS1-catalyzed nucleotide exchange and/or formation of the KRAS G12D/GTP/RAF1 complex, thereby inhibiting mutant KRAS-dependent signal transduction. MRTX1133 selectively inhibits KRAS G12D mutant, but not KRAS wild-type, tumor cells. MRTX1133 has single digit nanomolar activity in cellular assays and marked in vivo efficacy in tumor models harboring KRAS G12D mutations.

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

MRTX1133 Chemical Structure

MRTX1133 Chemical Structure

CAS No. : 2621928-55-8

Size Price Stock Quantity
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 674 In-stock
Solution
10 mM * 1 mL in DMSO USD 674 In-stock
Solid
1 mg USD 242 In-stock
5 mg USD 510 In-stock
10 mg USD 780 In-stock
50 mg   Get quote  
100 mg   Get quote  

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Based on 3 publication(s) in Google Scholar

MRTX1133 Related Antibodies

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  • References

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Description

MRTX1133 is a noncovalent, potent, and selective KRAS G12D inhibitor. MRTX1133 optimally fills the switch II pocket and extends three substituents to favorably interact with the protein, resulting in an estimated KD against KRAS G12D of 0.2 pM. MRTX1133 prevents SOS1-catalyzed nucleotide exchange and/or formation of the KRAS G12D/GTP/RAF1 complex, thereby inhibiting mutant KRAS-dependent signal transduction. MRTX1133 selectively inhibits KRAS G12D mutant, but not KRAS wild-type, tumor cells. MRTX1133 has single digit nanomolar activity in cellular assays and marked in vivo efficacy in tumor models harboring KRAS G12D mutations[1][2].

IC50 & Target

KRas G12D

0.2 pM (Kd)

In Vitro

MRTX1133 inhibits ERK phosphorylation in the AGS cell line with an IC50 ranging 1-10 nM (AsPC-1, Panc 04.03, Panc 02.03, SW1990, GP2D, Suit2, A427, SNU1033, and HPAC cells). In a 2D viability assay, the IC50 of MRTX1133 is 6 nM against AGS cells (KRAS G12D), while demonstrating more than 500-fold selectivity against MKN1, a cell line which is dependent on KRAS for its growth and survival due to the amplification of wild-type KRAS[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

MRTX1133 Related Antibodies
In Vivo

MRTX1133 displays efficacious in a KRAS G12D mutant xenograft mouse tumor model[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: 6-8-weekold, female, athymic nude-Foxn1nu mice (Panc 04.03 model)[1]
Dosage: 3, 10, or 30 mg/kg
Administration: Intraperitoneal; twice a day for 28 days
Result: An antitumor efficacy study in this model resulted in MRTX1133 dose-dependent antitumor activity with 94% growth inhibition observed at 3 mg/kg BID (IP) and tumor regressions of -62% and -73% observed at 10 and 30 mg/kg BID (IP), respectively.
Clinical Trial
Molecular Weight

600.63

Formula

C33H31F3N6O2
CAS No.
Appearance

Solid

Color

Yellow to brown

SMILES

OC1=CC(C2=C(F)C3=NC(OC[C@]45C[C@@H](F)CN4CCC5)=NC(N6C[C@H]7N[C@H](CC7)C6)=C3C=N2)=C8C(C#C)=C(F)C=CC8=C1
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 50 mg/mL (83.25 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.6649 mL 8.3246 mL 16.6492 mL
5 mM 0.3330 mL 1.6649 mL 3.3298 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
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Concentration
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Volume
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Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

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Volume (start)

V1

=
Concentration (final)

C2

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Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% SBE-β-CD/50 mM citrate pH 5.0

    Solubility: 10 mg/mL (16.65 mM); Clear solution; Need ultrasonic and warming and adjust pH to 5 with HCl and heat to 60°C

  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: 3.5 mg/mL (5.83 mM); Suspended solution; Need ultrasonic

    This protocol yields a suspended solution of 3.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (35.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.42%

COA (255 KB) HNMR (141 KB) RP-HPLC (138 KB)

Handling Instructions (2659 KB)
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.6649 mL 8.3246 mL 16.6492 mL 41.6230 mL
5 mM 0.3330 mL 1.6649 mL 3.3298 mL 8.3246 mL
10 mM 0.1665 mL 0.8325 mL 1.6649 mL 4.1623 mL
15 mM 0.1110 mL 0.5550 mL 1.1099 mL 2.7749 mL
20 mM 0.0832 mL 0.4162 mL 0.8325 mL 2.0811 mL
25 mM 0.0666 mL 0.3330 mL 0.6660 mL 1.6649 mL
30 mM 0.0555 mL 0.2775 mL 0.5550 mL 1.3874 mL
40 mM 0.0416 mL 0.2081 mL 0.4162 mL 1.0406 mL
50 mM 0.0333 mL 0.1665 mL 0.3330 mL 0.8325 mL
60 mM 0.0277 mL 0.1387 mL 0.2775 mL 0.6937 mL
80 mM 0.0208 mL 0.1041 mL 0.2081 mL 0.5203 mL
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MRTX1133 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

MRTX11332621928-55-8MRTX 1133MRTX-1133Rasfirst-in-classactiveinactivestatesmutantwild-typetumorcellsKRASG12DERKphosphorylationInhibitorinhibitorinhibit

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