RMC-8839
RMC-8839 is an orally active selective RAS (ON) G13C inhibitor with a Ki value of 28.3 nM. RMC-8839 disrupts the interaction between KRASG13C and RAF1 (RBD). RMC-8839 inhibits RAS-MAPK pathway signaling by reducing DUSP6 mRNA levels and pERK levels. RMC-8839 induces cytotoxicity, apoptosis (apoptosis) and antiproliferative effects in KRASG13C-mutated cells. RMC-8839 induces tumor stasis or regression in mice. RMC-8839 can be used in research related to non-small cell lung cancer.
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- CAS No.: 2953305-55-8
- 화학식: C54H72F3N9O8
- 분자량:1032.20
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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
- Protocol
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
[2]|
KRAS G13C 28.3 nM (Ki) |
In Vitro
RMC-8839 selectively reduces the viability of BEAS-2B cells expressing KRASG13C, with an IC25 of 7.5 nM[1].
RMC-8839 (5-625 nM; 0-4 h) disrupts the KRASG13C-RAF1 (RBD) complex in U-2 OS cells, exhibits 55-fold selectivity for mutant KRASG13C over wild-type KRAS, and has an EC50 of approximately 2 nM against KRASG13C[2].
RMC-8839 (10 pM-10 μM; 4 h) inhibits pERK in KRASG13C-mutant NCI-H1734 cells with an EC50 of approximately 3 nM, and exhibits 22-fold selectivity over wild-type RAS NCI-H1975 cells[2].
RMC-8839 (10 pM-10 μM; 5 days) inhibits the viability of NCI-H1734 cells harboring the KRASG13C mutation, with an EC50 of approximately 0.3 nM[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MLE-12 cells expressing FLAG-tagged KRAS variants
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Concentration:50 nM
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Incubation Time:6 h
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Result:Completely cross-linked FLAG-tagged KRASG13C and strongly inhibited ERK 1/2 phosphorylation in KRASG13C MLE-12 cells.
Caused only partial cross-linking and modest ERK 1/2 inhibition in KRASG12C cells.
Exerted no effect on other KRAS variants.
In Vivo
RMC-8839 (10-100 mg/kg; p.o.; once daily; for 28 consecutive days) exhibits dose-dependent tumor growth inhibition in the NCI-H1734 xenograft model[2].
RMC-8839 (100 mg/kg; p.o.; once daily; for 28 consecutive days) induces tumor regression in the ST2822B KRASG13C-mutant non-small cell lung cancer PDX model[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD SCID (female, 6-8 weeks old, subcutaneous xenograft model)[1]
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Dosage:100 mg/kg (monotherapy); 100 mg/kg + 5 mg/kg Docetaxel (HY-B0011) (combination)
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Administration:p.o.; daily; 28 days (monotherapy); p.o.; daily; 28 days + i.v.; single dose; day 0 (combination)
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Result:Induced tumor growth inhibition compared to vehicle control.
Drove significant tumor regression, with all nine tumors exhibiting greater than 80% tumor volume reduction when combined with Docetaxel.
Achieved statistically significant combination index scores of 0.077 (Highest Single Agent model) and 0.2333 (Bliss Independence model), where CI < 1 indicates synergy.
Was well-tolerated as measured by body weight assessment.
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Animal Model:NOD SCID (female, 6-8 weeks old)[2]
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Dosage:10 mg/kg; 25 mg/kg; 100 mg/kg (daily dosing for 28 days); 10 mg/kg; 50 mg/kg; 100 mg/kg (single dose)
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Administration:p.o.; daily; 28 days; p.o. (single dose)
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Result:Achieved >90% tumor target engagement within 3 hours and maintained above 75% for 24 hours with a single 100 mg/kg oral dose.
Reached >95% tumor RAS-MAPK pathway suppression (via human DUSP6 mRNA levels) and maintained above 80% for 24 hours with a single 100 mg/kg oral dose.
Slowed tumor growth with 10 mg/kg daily dosing for 28 days.
Further reduced tumor growth with 25 mg/kg daily dosing for 28 days.
Achieved tumor stasis with 100 mg/kg daily dosing for 28 days.
Showed sustained suppression of RAS pathway signaling in tumors collected 8 hours after the final dose of 25 mg/kg and 100 mg/kg.
Maintained stable body weight with all doses, indicating good tolerability.
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Animal Model:Crl:NU(NCr)-Foxn1nu (female, 6-12 weeks old)[2]
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Dosage:100 mg/kg
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Administration:p.o.; daily; 28 days
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Result:Induced tumor regressions after 28 days of daily 100 mg/kg dosing.
- RNA extraction experimental
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Cell Cytotoxicity Assay
- Mammalian live/dead viability and cytotoxicity staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- Apoptosis Solutions
- Cell Viability Determination by MTT Colorimetric Assay
Chemical Information
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CAS No. 2953305-55-8
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분자량 1032.20
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화학식 C54H72F3N9O8
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SMILES
C[C@H](OC)C1=[C@@]([C@@]2=C(CC(C)(C)COC([C@H]3NN(C([C@H](CN4CC5=CCC4)NC([C@H](C(C)C)N(C)C(N6CCC7(OCN(C(C=C)=O)[C@H]7C)CC6)=O)=O)=O)CCC3)=O)C8=C(C=CC5=C8)N2CC(F)(F)F)C=CC=N1
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
[1]. McDaid WJ, et al. Targeting KRAS codon 13 mutations using direct combination approaches in non-small cell lung cancer. Cancer Discov. 2026 Jun 22. [Content Brief]
[2]. Seamon KJ, et al. Selective Inhibition of KRASG13C Reveals an Increased Dependence on Wild-Type RAS Isoforms in Codon 13 RAS-Mutant Cancers. Cancer discovery. 2026 Jun 22. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
RMC-8839 Related Classifications
HY-184892 Related Classifications
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