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Art. -Nr.: HY-189222

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RP04340

RP04340 is an orally active, selective pan-KRAS PROTAC degrader. RP04340 hijacks the CRBN E3 ligase and the cellular proteasome system to degrade KRAS, without degrading HRAS, NRAS, or common CRBN neosubstrates. RP04340 inhibits KRAS downstream signaling pathways, including pERK and DUSP6. RP04340 exhibits anticancer activity in various KRAS-mutant cancers. RP04340 can be used to study kras-driven cancers, including pancreatic ductal adenocarcinoma, colorectal cancer, and lung adenocarcinoma.
(Pink: K-RAS ligand (HY-189223); Blue: Cereblon E3 ligase ligand; Black: linker (HY-W007836)).

Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.

CAS. Nr.: 3118096-98-0
Formel: C₅₆H₆₁F₅N₁₀O₅
Molecular Weight:1049.14

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

RP04340 Chemical Structure

CAS. Nr.: 3118096-98-0

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Use of MCE Products

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

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

RP04340 is an orally active, selective pan-KRAS PROTAC degrader. RP04340 hijacks the CRBN E3 ligase and the cellular proteasome system to degrade KRAS, without degrading HRAS, NRAS, or common CRBN neosubstrates. RP04340 inhibits KRAS downstream signaling pathways, including pERK and DUSP6. RP04340 exhibits anticancer activity in various KRAS-mutant cancers. RP04340 can be used to study kras-driven cancers, including pancreatic ductal adenocarcinoma, colorectal cancer, and lung adenocarcinoma^[1]. (Pink: K-RAS ligand (HY-189223); Blue: Cereblon E3 ligase ligand; Black: linker (HY-W007836)).

IC₅₀ & Target

^[1]

K-RAS

Cereblon

Alle PROTACs Isoform-spezifische Produkte anzeigen :

Alle Ras Isoform-spezifische Produkte anzeigen :

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Cellular Effect

Cell Line	Type	Value	Description	References
MIA PaCa-2	DC₅₀	2 nM	Degradation of KRAS protein in MIA PaCa-2 (KRAS G12C) cells incubated for 24 h measured by KRAS degradation immunoblot assay. Degradation of KRAS protein in MIA PaCa-2 (KRAS G12C) cells incubated for 24 h measured by KRAS degradation immunoblot assay.	42679154
NCI-H727	DC₅₀	13.1 nM	Degradation of KRAS protein in NCI-H727 (KRAS G12V) cells incubated for 24 h measured by KRAS degradation immunoblot assay. Degradation of KRAS protein in NCI-H727 (KRAS G12V) cells incubated for 24 h measured by KRAS degradation immunoblot assay.	42679154
MIA PaCa-2	IC50	8.8 nM	Antiproliferative activity against MIA PaCa-2 (KRAS G12C) cells assessed as reduction in cell viability incubated for 72 h by Cell Titer-Glo assay. Antiproliferative activity against MIA PaCa-2 (KRAS G12C) cells assessed as reduction in cell viability incubated for 72 h by Cell Titer-Glo assay.	42679154
NCI-H727	IC50	3.7 nM	Antiproliferative activity against NCI-H727 (KRAS G12V) cells assessed as reduction in cell viability incubated for 72 h by Cell Titer-Glo assay. Antiproliferative activity against NCI-H727 (KRAS G12V) cells assessed as reduction in cell viability incubated for 72 h by Cell Titer-Glo assay.	42679154

In Vitro

RP04340 (0-1000 nM; 24 h) is a potent selective KRAS degrader that achieves low nanomolar DC₅₀ values in KRAS^G12D AsPC-1, KRAS^G12C MIA PaCa-2, and KRAS^G12V NCI-H727 cell lines, with no observed activity against HRAS or NRAS^[1].
RP04340 (0.1-1000 nM; 72 h) demonstrates potent low nanomolar antiproliferative activity in KRAS^G12D AsPC-1, KRAS^G12C MIA PaCa-2, and KRAS^G12V NCI-H727 cell lines^[1].

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

Western Blot Analysis^[1]

Cell Line:

AsPC-1 (KRAS G12D), MIA PaCa-2 (KRAS G12C), NCI-H727 (KRAS G12V), PK-59 (KRAS G12D)
Concentration:

0, 0.1, 1, 10, 100, 1000 nM
Incubation Time:

24 h
Result:

Potently degrades KRAS protein across multiple KRAS mutant lines, with DC50 values of 13.5 nM (AsPC-1), 2 nM (MIA PaCa-2), 13.1 nM (NCI-H727), and achieves >80% Dmax for KRAS degradation.
Does not induce degradation of HRAS or NRAS even at 1000 nM in PK-59 cells.

Cell Viability Assay^[1]

Cell Line:

AsPC-1 (KRAS G12D), MIA PaCa-2 (KRAS G12C), NCI-H727 (KRAS G12V)
Concentration:

0.1, 1, 10, 100, 1000 nM
Incubation Time:

72 h
Result:

Exhibits high antiproliferative activity in the tested KRAS mutant cell lines, with IC50 values of 20.9 nM (AsPC-1), 8.8 nM (MIA PaCa-2), and 3.7 nM (NCI-H727).

Parmacokinetics

Species	Dose	Route	AUC
Mice^[1]	10 mg/kg	p.o.	1309 ng·h/mL

In Vivo

In a PK-59 KRAS^G12D mouse xenograft PK/PD study, a single oral administration of RP04340 (100 mg/kg; p.o.) achieves 56.7% KRAS protein degradation, and once-daily oral administration of 100 mg/kg for 15 consecutive days achieves 76.6% KRAS protein degradation and significantly inhibits downstream oncogenic signaling^[1].
RP04340 (25-100 mg/kg; p.o.; once daily; 21 days) induces dose-dependent tumor regression in the MIA PaCa-2 KRAS^G12C xenograft model, with a tumor regression rate of up to 59.5% at a dose of 100 mg/kg^[1].
RP04340 (25-100 mg/kg; p.o.; once daily; 28 days) administered orally once daily for 28 days in the NCI-H727 KRAS^G12V xenograft model achieves a tumor growth inhibition rate of 75.4% at a dose of 100 mg/kg^[1].

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

Animal Model:

Balb/c nude mice (6-8 week old female)^[1]
Dosage:

100 mg/kg (single administration); 100 mg/kg (once daily for 15 consecutive days)
Administration:

p.o. (single administration); p.o. (once daily for 15 consecutive days)
Result:

Reached 1013 ng/g tumor RP04340 concentration (vs 278 ng/mL in plasma), 56.7% KRAS protein degradation, 67% pERK suppression, and 47% DUSP6 suppression after a single 100 mg/kg oral dose.
Reached 20133 ng/g tumor RP04340 concentration at 24 h (vs 1032 ng/mL in plasma), 76.6% KRAS protein degradation, 75% pERK inhibition, 99.8% DUSP6 suppression, and 18712 h·ng/mL steady-state AUC_0-24 in plasma after 15 consecutive 100 mg/kg once-daily oral doses.

Animal Model:

Balb/c nude mice (6-8 week old female)^[1]
Dosage:

25 mg/kg; 50 mg/kg; 100 mg/kg
Administration:

p.o.; once daily; 21 days
Result:

Achieved 15.1% tumor regression after 21 days of continuous dosing at the 25 mg/kg once-daily dose.
Produced 27.2% tumor regression after 21 days of continuous dosing at the 50 mg/kg once-daily dose.
Resulted in 59.5% tumor regression after 21 days of continuous dosing at the 100 mg/kg once-daily dose.

Animal Model:

Balb/c nude mice (6-8 week old female)^[1]
Dosage:

25 mg/kg; 50 mg/kg; 100 mg/kg
Administration:

p.o.; once daily; 28 days
Result:

Resulted in 60.3% tumor growth inhibition after 28 days of continuous administration at the 25 mg/kg once-daily dose.
Yielded 60.9% tumor growth inhibition after 28 days of continuous administration at the 50 mg/kg once-daily dose.
Produced 75.4% tumor growth inhibition after 28 days of continuous administration at the 100 mg/kg once-daily dose.

Chemical Information

CAS. Nr. 3118096-98-0
Molecular Weight 1049.14
Formel C₅₆H₆₁F₅N₁₀O₅
SMILES

O=C(N(C1=NN(C)C2=CC(C3CCN(C4CC5(CCN(C[C@]6(COC7=NC(N(CCC8)C[C@]98CCO9)=C(C=NC(C%10=C%11C(CC)=C(F)C=CC%11=CC(O)=C%10)=C%12F)C%12=N7)C(F)(F)C6)CC5)C4)CC3)=C(F)C=C12)CC%13)NC%13=O
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Reinheit & Dokumentation

Handling Instructions (2659 KB)

Verweise

[1]. Ji X, et al. Discovery and Characterization of RP04340: A Highly Potent and Orally Active Pan-KRAS PROTAC Degrader. Journal of medicinal chemistry. 2026 Aug 27;69(16):19982-19998.

Calculators

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)}

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.

Bioz

MOQ

Minimum order quantity

100 mg

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Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise

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RP04340

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle Ras Isoform-spezifische Produkte anzeigen

Alle ERK Isoform-spezifische Produkte anzeigen