RMC-9945
Based on 1 Customer Validation
RMC-9945 (RM-044) is a selective, covalent, and orally active RAS (ON) G12D inhibitor. RMC-9945 enhances the transcriptional activity of β-Catenin/TCF. RMC-9945 induces cell state transition, forcing metastatic colorectal cancer cells to switch from the Emp1+ state to the Lgr5+ stem cell-like state. RMC-9945 achieves durable disease control in preclinical models of colorectal cancer with early liver metastasis, but shows reduced activity in late-stage metastasis models. RMC-9945 can be used in research related to metastatic colorectal cancer and pancreatic ductal adenocarcinoma.
For research use only. We do not sell to patients.
- Purity: 98.20%
- CAS No.: 2922732-38-3
- Formula: C60H80F3N11O6S
- Molecular Weight:1140.41
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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KRas G12D |
RMC-9945 (100 nM) transiently inhibits the growth of AKTP MTO in vitro, induces the transition from the Emp1+ HRC state to the Lgr5+ CSC state, and enhances the transcriptional activity of β-catenin/TCF by upregulating TCF/LEF transcription factors[1].
RMC-9945 (100 nM; 4-10 days) induces the transition from the EMP1+ HRC state to the LGR5+ CSC state in KRASG12D-mutated colorectal cancer organoids, and its growth inhibitory activity varies across different models[1].
RMC-9945 (100 nM) alters chromatin accessibility in AKTP MTO, reduces the regulatory effect of AP1 on HRC-related genes, and enhances the regulatory effect of LEF/TCF on Lgr5+ CSC-related genes, without inducing large-scale changes in chromatin topology[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
RMC-9945 (100 mg/kg; p.o.; once daily; for 28 consecutive days) inhibits preneoplastic lesion burden in KPC mice, delays PDAC tumorigenesis, extends median overall survival by approximately 80 days, and does not select for more aggressive tumors[3].
RMC-9945 (100 mg/kg; p.o.; once daily; for 10 consecutive days) significantly reduces pancreatic tumor burden in KPC mice by inducing apoptosis of tumor epithelial cells while inhibiting the RAS signaling pathway[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J mice (syngeneic, liver metastases induced by AKTP mouse tumor organoid inoculation into spleen)[1]
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Dosage:100 mg/kg (monotherapy); 100 mg/kg + DT 25 μg/kg (combination therapy)
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Administration:p.o.; daily; 11 days (day 15 initiation); p.o.; daily; 7 days + i.p.; every other day; 2 weeks (day 21 initiation combination); p.o.; daily; 10 days + i.p.; daily; 6 days (day 14 initiation combination); p.o.; daily; 6 days (transcriptional analysis)
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Result:Reduced the number and size of liver metastatic nodules when treatment started at day 15, though many persisted as drug-tolerant lesions.
Exerted limited therapeutic activity when treatment started at day 21 or 25, with metastases continuing to grow and no significant reduction in metastatic burden.
Induced transcriptional reprogramming of metastases, depleting Emp1+ high-relapse cells and enriching Lgr5+ cancer stem cells, with a significant increase in Lgr5 mRNA-positive cells (P < 0.0001 for both day 21 and day 15 initiation).
Reduced liver nodule number by twofold with monotherapy starting at day 21.
Reduced metastasis size threefold when combined with DT-mediated Lgr5+ CSC ablation starting at day 21.
Arrested metastatic outgrowth when treatment started at day 14.
Reduced metastatic load 10- to 11-fold when combined with DT starting at day 14, compared with either monotherapy.
Significantly extended mouse survival when combined with DT starting at day 14, compared with vehicle, RMC-9945 alone, or DT alone (P < 0.0001 for all comparisons).
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Animal Model:KPC (9-week-old; genetically engineered to carry KrasG12D and Tp53R172H mutations; autochthonous model with spontaneous progression from acinar-to-ductal metaplasia to pancreatic intraepithelial neoplasia to invasive PDAC)[3]
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Dosage:100 mg/kg
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Administration:p.o.; daily; 10 days
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Result:Significantly reduced the percentage area of preneoplastic tissue (PanIN and acinar-to-ductal metaplasia) compared to vehicle controls.
Markedly diminished phosphorylated extracellular signal-regulated kinase (pERK) staining after 3 days of treatment.
Increased staining for cleaved caspase 3 in residual PanIN lesions, indicating induction of apoptotic cell death.
Left amylase staining (an acinar cell marker) unchanged relative to controls.
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Animal Model:KPC (7-week-old; genetically engineered to carry KrasG12D and Tp53R172H mutations; autochthonous model with spontaneous progression from acinar-to-ductal metaplasia to pancreatic intraepithelial neoplasia to invasive PDAC)[3]
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Dosage:100 mg/kg
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Administration:p.o.; daily; 28 days
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Result:Suppressed preneoplastic burden to an extent greater than or equivalent to 10 days of treatment; fully eliminated detectable preneoplasia in 2 of 5 animals.
Significantly delayed tumor onset (median age at tumor onset 162 days versus 83 days in vehicle controls; P < 0.0001).
Prolonged median overall survival by ~80 days (median age at death 200 days versus 120 days in vehicle controls; P < 0.0001).
Left size at diagnosis and growth rate of tumors that emerged after interception similar to vehicle control tumors; left overall survival measured from tumor detection comparable to controls.
Chemical Information
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CAS No. 2922732-38-3
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Appearance Solid
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Molecular Weight 1140.41
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Formula C60H80F3N11O6S
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Color White to off-white
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SMILES
FC(F)(F)CN1[C@]([C@]2=C(N=CC(N3CCN(C4CC4)CC3)=C2)[C@H](C)OC)=C5C6=CC(C7=CSC(C[C@@H](C(N8N[C@](CCC8)([H])C(OCC(C)(C5)C)=O)=O)NC([C@@H](N9C[C@]%10(CN(CC%10)C([C@H]%11[C@@H](C%12CC%12)N%11C)=O)CC9)C(C)C)=O)=N7)=CC=C61
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Synonyms
RM-044
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
DMSO : 100 mg/mL (87.69 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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.
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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (2.19 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.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
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).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
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
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Data Sheet (286 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Handling Instructions (2659 KB)
References
[1]. Centonze A, et al. A Plastic EMP1+ to LGR5+ Cell State Conversion as a Bypass to KRASG12D Pharmacologic Inhibition in Metastatic Colorectal Cancer. Cancer discovery. 2026 Feb 06;16(2):320-344. [Content Brief]
[2]. Bu J, et al. Cancer Stem Cells in Human Gastrointestinal and Hepatic Cancers. MedComm (2020). 2025 Dec 3;6(12):e70513. doi: 10.1002/mco2.70513. [Content Brief]
[3]. Vincent A, et al. Pancreatic cancer. Lancet (London, England). 2011 Aug 13;378(9791):607-20. [Content Brief]
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 |
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| DMSO | 1 mM | 0.8769 mL | 4.3844 mL | 8.7688 mL | 21.9219 mL |
| 5 mM | 0.1754 mL | 0.8769 mL | 1.7538 mL | 4.3844 mL | |
| 10 mM | 0.0877 mL | 0.4384 mL | 0.8769 mL | 2.1922 mL | |
| 15 mM | 0.0585 mL | 0.2923 mL | 0.5846 mL | 1.4615 mL | |
| 20 mM | 0.0438 mL | 0.2192 mL | 0.4384 mL | 1.0961 mL | |
| 25 mM | 0.0351 mL | 0.1754 mL | 0.3508 mL | 0.8769 mL | |
| 30 mM | 0.0292 mL | 0.1461 mL | 0.2923 mL | 0.7307 mL | |
| 40 mM | 0.0219 mL | 0.1096 mL | 0.2192 mL | 0.5480 mL | |
| 50 mM | 0.0175 mL | 0.0877 mL | 0.1754 mL | 0.4384 mL | |
| 60 mM | 0.0146 mL | 0.0731 mL | 0.1461 mL | 0.3654 mL | |
| 80 mM | 0.0110 mL | 0.0548 mL | 0.1096 mL | 0.2740 mL |
RMC-9945 Related Classifications
HY-186001 Related Classifications
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- RMC-9945
- 2922732-38-3
- RM-044
- RMC9945
- RMC 9945
- RM044
- RM 044
- Ras
- β-catenin
- cyclophilin A
- pancreatic ductal adenocarcinoma
- tumor-prone mice
- metastatic colorectal cancer cells
- Emp1+
- KPC mice
- KRASG12D
- Lgr5+
- KRASG12D-mutant patient-derived colorectal cancer organoids
- neoplastic pancreatic epithelial cells
- Inhibitor
- inhibitor
- inhibit