Art. -Nr.: HY-156498

RMC-7977

17 Cited Publications

Kundenbewertung

Based on 17 publication(s) in Google Scholar

RMC-7977 is an orally active triple-complex RAS inhibitor that can simultaneously bind to cyclophilin A (CYPA) (K_d = 195 nM) and KRAS (G12V) (K_d = 292 μM). It exhibits broad-spectrum inhibitory activity against KRAS, NRAS, and HRAS proteins and their various wild-type and mutant variants. RMC-7977 induces apoptosis by inhibiting the phosphorylation of ERK, CRAF, and RSK, as well as increasing PARP cleavage. This leads to tumor regression, reduces resistance in KRAS^G12C cancer models, and demonstrates good tolerability across various RAS cancer models.

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Reinheit: 99.48%
CAS. Nr.: 2765082-12-8
Formel: C₄₇H₆₀N₈O₆S
Molecular Weight:865.11

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

RMC-7977 Chemical Structure

CAS. Nr.: 2765082-12-8

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Publications (17)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target

C-Raf

KRAS(G12C)

H-Ras

NRAS rG4

Alle Ras Isoform-spezifische Produkte anzeigen :

Alle ERK Isoform-spezifische Produkte anzeigen :

Alle Raf Isoform-spezifische Produkte anzeigen :

Alle Ribosomal S6 Kinase (RSK) Isoform-spezifische Produkte anzeigen :

Alle AMPK Isoform-spezifische Produkte anzeigen :

Alle PARP Isoform-spezifische Produkte anzeigen :

In Vitro

RMC-7977 (3-300 nM, 24 h) exhibits inhibitory activity on the KRAS signaling pathway in mouse embryonic fibroblasts (MEFs, Ras gene-deficient, restored by introducing wild-type or mutant KRAS genes to express KRAS protein)^[1].
RMC-7977 (0.1-10 nM, 48 h) inhibits proliferation and downstream signaling (i.e., decreases pERK levels) in RAS-dependent cancer cells (i.e., cancer cells with RAS pathway activation due to mutations in KRAS, NRAS, or EGFR) in a concentration-dependent manner^[1].
RMC-7977 (1-100 nM, 48 h) can induce apoptosis in KRAS^G12V and KRAS^G12C cells by inhibiting the phosphorylation of RAF, ERK, and RSK, and increasing PARP cleavage^[1].
RMC-7977 (5-33 nM, 96 h) inhibits the proliferation of acute myeloid leukemia (AML) cell lines driven by FLT3-ITD (Molm-14, MV4-11), KIT (Kasumi-1, SKNO-1), and RAS mutations (NRAS - OCIAML-3, HL-60, KRAS - NOMO-1) with an IC₅₀ value in the range of 5-33 nM and also inhibits MAPK pathway signaling^[2].

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

Cell Viability Assay^[1]

Cell Line:

KRAS^G12X mutant cell lines; KRAS wild-type cell lines, NRAS and HRAS mutant cell lines; Human cancer cell lines with mutations or fusions of EGFR, ERBB3, FGFR1, FGFR2, FGFR3, ROS1, RET, NTRK1, and ALK; Wild-type MET gene amplification cell line
Concentration:

0-1 μM
Incubation Time:

4 h
Result:

Exhibited strong inhibitory effects on KRAS^G12X mutant cell lines, with a median EC₅₀ of 2.40 nM.
Exhibited inhibitory effects on KRAS wild-type genotypes, including NRAS and HRAS mutant cell lines (median EC₅₀ = 6.76 nM), as well as cell lines with mutations or fusions of EGFR, ERBB3, FGFR1, FGFR2, FGFR3, ROS1, RET, NTRK1, and ALK (median EC₅₀ = 6.14 nM).
Exhibited inhibitory effects on cell lines with wild-type MET gene amplification (median EC₅₀ = 6.61 nM).

Western Blot Analysis^[1]

Cell Line:

RAS-less mouse embryonic fibroblasts (MEFs) (introduced with exogenous wild-type or mutant KRAS genes or BRAF(V600E))
Concentration:

3, 10, 30, 100, 300 nM
Incubation Time:

24 h
Result:

Suppressed pERK in all KRAS-expressing cells, but not in BRAF(V600E)-expressing RAS-less MEFs.

In Vivo

Compared to using RMC-4550 (HY-116009, a SHP2 inhibitor) and Coibmetinib (a MEK inhibitor) to inhibit RAS-MAPK downstream signaling pathway activity, directly targeting active RAS with RMC-7977 (10 mg/kg, p.o., once daily for 5 consecutive days per week followed by 2 days of cessation, for a total of 28 days) demonstrates superior anti-tumor activity in xenograft KRASG12X mouse models^[1].
RMC-7977 (10 mg/kg, p.o., once daily for 5 days per week followed by 2 days off, for a total of 90 days) demonstrates significant anti-tumor activity in PDAC, CRC, and NSCLC models with KRASG12X mutations and in xenograft mice models, induces durable tumor regression, and shows good tolerability in the mouse models^[1].
RAS inhibition mediated by RMC-7977 (10 mg/kg, oral administration, once daily for 28 days) does not impair immune cell function in immunocompetent mice^[1].
RMC-7977 (10 mg/kg, p.o., once daily for 28 days) can inhibit the adaptive resistance to KRAS(G12C) inhibitors in a PDX mice model with KRAS(G12C) mutations (derived from NSCLC tumor cells that relapsed after Sotorasib (HY-114277) treatment)^[1].
RMC-7977 (10-50 mg/kg, p.o., single dose) effectively inhibits RAS-MAPK signaling in human pancreatic ductal adenocarcinoma (PDAC) xenograft mouse models (Capan-1 (KRASG12V)) and maintains high concentrations in tumor tissue^[3].

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

Animal Model:

Subcutaneously implanted NCI-H441 CDX model of non-small cell lung cancer xenograft tumor (NSCLC) in BALB/c mice^[1]
Dosage:

10 mg/kg
Administration:

Oral gavage (p.o.), single dose or once daily for 5 days, followed by a 2-day break, totally for 28 days
Result:

Had an EC50 value of 130 nM for DUSP6 in the NCI-H441 non-small cell lung cancer (NSCLC) model.
Was well tolerated and resulted in 83% mean tumour regression following 28 days of treatment in the NCI-H441 model.
Was sufficient to maximally suppress tumour DUSP6 levels (91%) at 8 h at a single oral dose.
Was observed to have prolonged exposure in tumors, with overall exposure in subcutaneous tumors increasing approximately threefold compared to blood.

Animal Model:

PDAC, CRC, NSCLC CDX and patient-derived xenograft (PDX) mice models (bearing KRASG12X mutations)^[1]
Dosage:

10 mg/kg
Administration:

Oral gavage (p.o.), once daily for 90 days
Result:

Caused tumor regression in 9 out of 15 (60%) RAS-addicted cancer mouse models after 4 to 6 weeks of administration.
Had minimal effects on body weight across all models.
Exhibited anti-tumor activity and maintained cytostatic responses after extending the administration to 90 days.

Animal Model:

Human Clinical-Derived Xenograft mice model of PDAC (Capan-1 (KRASG12V))^[3]
Dosage:

10, 25, 50 mg/kg
Administration:

Oral gavage, single dose
Result:

Was exposed in Capan-1 xenograft tumors for three times longer than in the blood.
Inhibited DUSP6 levels within 24-48 hours, with an EC₅₀ of 142 nM.

Chemical Information

CAS. Nr. 2765082-12-8
Appearance Solid
Molecular Weight 865.11
Formel C₄₇H₆₀N₈O₆S
Color White to light yellow
SMILES

CO[C@H](C1=[C@@](C=C(N2CCN(C3CC3)CC2)C=N1)[C@@](N4CC)=C(C5=C4C=CC6=C5)CC(C)(C)COC([C@@H](N7)CCCN7C([C@@H](NC([C@@H]8[C@@H]9[C@H]8COC9)=O)CC%10=NC6=CS%10)=O)=O)C
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Publications (17)

All WBCell Proliferation/Viability AssayIFELISA

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Journal Impact Factor

Signal Transduct Target Ther

Vertical RAS pathway inhibition in pancreatic cancer drives therapeutically exploitable mitochondrial alterations. [Abstract]

2026 Jan 16;11(1):33. PMID: 41545339
Cancer Cell

2026 May 21:S1535-6108(26)00220-5. PMID: 42167227
Cancer Res

Combined Inhibition of HRAS and MEK Induces Tumor Regression and Restores Myogenic Differentiation in HRAS-Mutant Rhabdomyosarcoma. [Abstract]

2026 Feb 11. PMID: 41671396
Nat Commun

Intrinsic resistance to RAS inhibitors is driven by dysregulation of KRAS degradation. [Abstract]

2025 Dec 15. PMID: 41397976

RMC-7977 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Dec 15. [Abstract]

Immunoblotting for total KRAS in H727 cells expressing shGFP or shLZTR1 and treated with RMC7977 (10 or 30 nM, 24 h). Vinculin and total KRAS were detected on the same gel.

RMC-7977 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Dec 15. [Abstract]

The IC50 of RMC7977 was measured by monitoring the growth of A427 cells expressing shGFP or shLZTR1 using Incucyte. Data are presented as means ± SEM; n = 3 technical replicates per group.

RMC-7977 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Dec 15. [Abstract]

Immunofluorescence analysis using antibodies against LAMP1 and mTOR in H727 cells expressing shGFP or shLZTR1 treated with RMC7977 (10 nM, 24 h) or DMSO. Scale bar 20 µm.

RMC-7977 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Dec 15. [Abstract]

ELISA-measured VEGFA levels in the supernatant of H727 cells treated with DMSO or RMC7977 (10 nM, 24 h).

RMC-7977 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Dec 15. [Abstract]

Immunofluorescence analysis of H727 cells expressing shGFP or shLZTR1 after DMSO- or RMC7977 (10 nM, 24 h)-treated H727 cells using the indicated antibodies. Scale bar 20 µm.
Sci Adv

Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis. [Abstract]

2025 Jan 24;11(4):eadq2395. PMID: 39841821
Cell Death Dis

Simultaneous targeting of KRAS and CDK4 synergistically induces durable growth arrest in pancreatic cancer cells. [Abstract]

2025 Dec 23. PMID: 41436723
Int J Mol Sci

The Rab18/Ras/ERK/FosB/MMP3 Signaling Pathway Mediates Cell Migration Regulation by 2'3'-cGAMP. [Abstract]

2025 Jun 16;26(12):5758. PMID: 40565221
SSRN

2026 Apr 18.
bioRxiv

Characterization and therapeutic suppression of KEAP1-NRF2-driven resistance to KRAS inhibitors in pancreatic and lung cancer. [Abstract]

2026 Apr 21:2026.04.18.719329. PMID: 42079131
bioRxiv

Tumor nutrient stress gives rise to a drug tolerant cell state in pancreatic cancer. [Abstract]

2025 Sep 8:2025.09.04.673818. PMID: 40964288
medRxiv

Modelling Acral Melanoma in Admixed Brazilians Uncovers Genomic Drivers and Targetable Pathways. [Abstract]

2025 Aug 13:2025.08.08.25332963. PMID: 40832384
bioRxiv

Post-Translational Modifications Remodel Proteome-Wide Ligandability. [Abstract]

2025 Aug 2:2025.07.31.667978. PMID: 40766426
bioRxiv

Thioredoxin Reductase 1 inhibition triggers ferroptosis in KRAS-independent lung cancers. [Abstract]

2025 Jul 30:2025.07.25.666783. PMID: 40766571
bioRxiv

Modeling acquired TKI resistance and effective combination therapeutic strategies in murine RET+ lung adenocarcinoma. [Abstract]

2025 Jun 7:2025.06.04.657911. PMID: 40502048
bioRxiv

2025 April 17.
ASPET Discov

2025 Mar 19.
Research Square Preprint

2024 Dec 02.

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 100 mg/mL (115.59 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.1559 mL

5.7796 mL

11.5592 mL

5 mM

0.2312 mL

1.1559 mL

2.3118 mL

10 mM

0.1156 mL

0.5780 mL

1.1559 mL

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.

Molaritätsrechner

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

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

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

Stock Solution Working Solution

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: 2% DMSO 40% PEG300 5% Tween-80 53% Saline

Solubility: ≥ 2 mg/mL (2.31 mM); Clear solution

Protocol 2

Add each solvent one by one: 2% DMSO 98% (20% SBE-β-CD in Saline)

Solubility: 2 mg/mL (2.31 mM); Suspended solution; Need ultrasonic

Protocol 3

Add each solvent one by one: 2% DMSO 98% Corn Oil

Solubility: ≥ 2 mg/mL (2.31 mM); Clear solution

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (288 KB)
SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Singh M, et al. Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy. Research Square; 2023. [Content Brief]

[2]. Popescu B, et al. RAS MULTI (ON) inhibitor RMC-7977 targets oncogenic RAS mutations and overcomes RAS/MAPK-mediated resistance to FLT3 inhibitors in AML models[J]. Blood, 2023, 142: 2793.

[3]. Wasko UN, et al. Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer. Nature. 2024 May;629(8013):927-936. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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	1.1559 mL	5.7796 mL	11.5592 mL	28.8981 mL
	5 mM	0.2312 mL	1.1559 mL	2.3118 mL	5.7796 mL
	10 mM	0.1156 mL	0.5780 mL	1.1559 mL	2.8898 mL
	15 mM	0.0771 mL	0.3853 mL	0.7706 mL	1.9265 mL
	20 mM	0.0578 mL	0.2890 mL	0.5780 mL	1.4449 mL
	25 mM	0.0462 mL	0.2312 mL	0.4624 mL	1.1559 mL
	30 mM	0.0385 mL	0.1927 mL	0.3853 mL	0.9633 mL
	40 mM	0.0289 mL	0.1445 mL	0.2890 mL	0.7225 mL
	50 mM	0.0231 mL	0.1156 mL	0.2312 mL	0.5780 mL
	60 mM	0.0193 mL	0.0963 mL	0.1927 mL	0.4816 mL
	80 mM	0.0144 mL	0.0722 mL	0.1445 mL	0.3612 mL
	100 mM	0.0116 mL	0.0578 mL	0.1156 mL	0.2890 mL

RMC-7977

17 Cited Publications

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RMC-7977

Publications Citing Use of MedChemExpress (MCE) RMC-7977

Alle Ras Isoform-spezifische Produkte anzeigen

Alle ERK Isoform-spezifische Produkte anzeigen

Alle Raf Isoform-spezifische Produkte anzeigen

Alle Ribosomal S6 Kinase (RSK) Isoform-spezifische Produkte anzeigen

Alle AMPK Isoform-spezifische Produkte anzeigen

Alle PARP Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (17)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

RMC-7977 Related Classifications

HY-156498 Related Classifications