2. GPCR/G Protein MAPK/ERK Pathway Apoptosis
  3. Ras Apoptosis
  4. RMC-5127

RMC-5127 is a small molecule inhibitor that binds to GTP-targeted KRASG12V, with oral bioavailability and blood-brain barrier permeability. RMC-5127 inhibits the activities of the RAS and MAPK pathways, suppresses the proliferation of KRASG12V-mutant cancer cells and induces their apoptosis. RMC-5127 can be used for the research of KRASG12V-mutant non-small cell lung cancer, pancreatic ductal adenocarcinoma, colorectal cancer and intracranial KRASG12V tumors.

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

RMC-5127

RMC-5127 Chemical Structure

CAS No. : 3082166-76-2

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
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RMC-5127 Related Antibodies

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Description

RMC-5127 is a small molecule inhibitor that binds to GTP-targeted KRASG12V, with oral bioavailability and blood-brain barrier permeability. RMC-5127 inhibits the activities of the RAS and MAPK pathways, suppresses the proliferation of KRASG12V-mutant cancer cells and induces their apoptosis. RMC-5127 can be used for the research of KRASG12V-mutant non-small cell lung cancer, pancreatic ductal adenocarcinoma, colorectal cancer and intracranial KRASG12V tumors[1].

IC50 & Target

KRas G12V

 

In Vitro

RMC-5127 (10-11 M to 10-6 M) potently disrupts KRASG12V-RAF binding in a cellular NanoBRET assay with a median EC50 of 2.1 nM and 93% median maximum inhibition, demonstrating 26-fold selectivity over K/N/HRAS wildtype[1].
RMC-5127 (10-12 M to 10-6 M) potently inhibits MAPK pathway activity in CAPAN-1 (KRASG12V) cells with an IC50 of 0.6 nM for pERK inhibition[1].
RMC-5127 suppresses RAS pathway activity, inhibits proliferation, and induces apoptosis in a panel of KRASG12V mutant human cancer cells, with a median maximum proliferation inhibition of 93%, while only causing submaximal inhibition in K/N/HRAS wildtype cancer cells[1].

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

RMC-5127 Related Antibodies
Parmacokinetics
Species Dose Route Brain Concentration
Mice[1] 100 mg/kg p.o. 568 nM
In Vivo

RMC-5127 (3-200 mg/kg; p.o.; once daily; up to 40 days) drives dose-dependent, profound anti-tumor activity in subcutaneous NCI-H441 KRASG12V/WT NSCLC xenografts, with complete or near-complete tumor regression achieved at doses of 100 mg/kg and 200 mg/kg once daily[1].
RMC-5127 (3-200 mg/kg; p.o.; single dose) achieves dose-dependent exposure in blood and NCI-H441 KRASG12V/WT tumors, with MAPK pathway inhibition (measured by DUSP6 mRNA suppression) having an EC50 of 157 nM[1].
RMC-5127 (100 mg/kg; p.o.; once daily; 7 days) achieves measurable brain exposure in naive BALB/c mice, with a brain-to-blood concentration ratio of 0.14 at 4 hours post-last dose[1].
RMC-5127 (100-200 mg/kg; p.o.; once daily; up to 70 days) drives durable anti-tumor activity in intracranial NCI-H441-Luc KRASG12V/WT NSCLC xenografts, with profound tumor regression achieved at a dose of 200 mg/kg once daily[1].

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

Animal Model: Immunodeficient mice (n=3 per time point)[1]
Dosage: 3 mg/kg; 10 mg/kg; 30 mg/kg; 100 mg/kg; 200 mg/kg
Administration: p.o.; single dose
Result: Demonstrated dose-dependent exposure in both blood and tumor, with compound elimination slower in tumors than in blood.\nInduced dose-dependent inhibition of DUSP6 mRNA expression in tumors, with an EC50 of 157 nM interpolated from the PK/PD relationship curve.
Animal Model: BALB/c mice (naive, n=3 per time point)[1]
Dosage: 100 mg/kg
Administration: p.o.; once daily; 7 days
Result: Achieved total brain concentration of 568 nM, with a brain-to-blood concentration ratio of 0.14 at 4 hours post-last dose.\nMaintained measurable brain exposure at 24 hours post-last dose, with concentration levels similar to those seen at 4 hours post-last dose in tumor-bearing mice given a single 100 mg/kg dose.
Clinical Trial
Molecular Weight

1062.33

Formula

C57H75N9O9S
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

C[C@H](OC)C1=[C@@]([C@@]2=C(CC(C)(C)COC([C@H]3NN(C([C@@H](NC([C@H]4OC[C@@H]4C)=O)[C@@H]5N6CC7(COC7)C6)=O)C8CC3C8)=O)C9=C(C=CC(C%10=CSC5=N%10)=C9)N2CCOC%11CCOCC%11)C=C(N%12CCN(C%13CC%13)CC%12)C=N1
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 : 100 mg/mL (94.13 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 0.9413 mL 4.7066 mL 9.4133 mL
5 mM 0.1883 mL 0.9413 mL 1.8827 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.

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  • Dilution Calculator

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

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

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

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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% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (2.35 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (2.35 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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mg/kg

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(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 +
% 
+
%
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%
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: 99.96%

SDS (251 KB)

COA (262 KB) HNMR (363 KB) RP-HPLC (250 KB) MS (231 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 0.9413 mL 4.7066 mL 9.4133 mL 23.5332 mL
5 mM 0.1883 mL 0.9413 mL 1.8827 mL 4.7066 mL
10 mM 0.0941 mL 0.4707 mL 0.9413 mL 2.3533 mL
15 mM 0.0628 mL 0.3138 mL 0.6276 mL 1.5689 mL
20 mM 0.0471 mL 0.2353 mL 0.4707 mL 1.1767 mL
25 mM 0.0377 mL 0.1883 mL 0.3765 mL 0.9413 mL
30 mM 0.0314 mL 0.1569 mL 0.3138 mL 0.7844 mL
40 mM 0.0235 mL 0.1177 mL 0.2353 mL 0.5883 mL
50 mM 0.0188 mL 0.0941 mL 0.1883 mL 0.4707 mL
60 mM 0.0157 mL 0.0784 mL 0.1569 mL 0.3922 mL
80 mM 0.0118 mL 0.0588 mL 0.1177 mL 0.2942 mL
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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:

RMC-51273082166-76-2RMC5127RMC 5127RasApoptosisxenograft modelsMAPK pathwayKRAS^{G12V}BALB/c miceapoptosispancreatic ductal adenocarcinomaRAS pathwayCAPAN-1 cellscolorectal cancernon-small cell lung cancerInhibitorinhibitorinhibit

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