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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- No. CAS: 2953305-55-8
- Fòrmula: C54H72F3N9O8
- Peso molecular:1032.20
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Almacenamiento:
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Actividad biológica
Descripciòn
IC50 & Target
[2]|
KRAS G13C 28.3 nM (Ki) |
In Vitro
RMC-8839 (50 nM; 6-72 h) potently and selectively reduces the viability of MLE-12 cells expressing KRASG13C and inhibits the MAPK signaling pathway, with an IC50 of 135 nM, while exhibiting extremely low activity against other KRAS mutants[1].
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].
RMC-8839 (100 nM; 24-168 h) selectively inhibits the MAPK signaling pathway and reduces the viability of H1734, MOR, HCC4087, and H1355 cell lines with IC50 values of 20.3, 43.5, 477, and 1202 nM, respectively, while inducing apoptosis in sensitive KRASG13C cell lines[1].
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 mice 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 nude mouse 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.
Chemical Information
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No. CAS 2953305-55-8
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Peso molecular 1032.20
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Fòrmula 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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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[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)
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