Art. -Nr.: HY-176134

RP03707

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RP03707 is a PROTAC degrader of KRAS^G12D. RP03707 forms a ternary complex with KRAS^G12D and the CRBN E3 ligase, promoting the ubiquitination and proteasomal degradation of KRAS^G12D. RP03707 inhibits the growth of KRAS^G12D-positive tumor cells.
(Pink: KRas G12D ligand (HY-134813); Blue: Cereblon ligand (HY-49385); Black: linker (HY-176137)).

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Reinheit: 98.00%
CAS. Nr.: 3030493-05-8
Formel: C₅₅H₅₈F₃N₁₁O₄
Molecular Weight:994.12

Speicherung:

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

RP03707 Chemical Structure

CAS. Nr.: 3030493-05-8

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Biologische Aktivität
- Beschreibung
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

RP03707 is a PROTAC degrader of KRAS^G12D. RP03707 forms a ternary complex with KRAS^G12D and the CRBN E3 ligase, promoting the ubiquitination and proteasomal degradation of KRAS^G12D. RP03707 inhibits the growth of KRAS^G12D-positive tumor cells^[1]. (Pink: KRas G12D ligand (HY-134813); Blue: Cereblon ligand (HY-49385); Black: linker (HY-176137)).

Alle PROTACs Isoform-spezifische Produkte anzeigen :

Alle Ras Isoform-spezifische Produkte anzeigen :

In Vitro

RP03707 (0.0025-50 nM; 0-72 h) potently and rapidly degrades KRAS^G12D protein in AsPC-1 cells, with a DC₅₀ of 0.6 nM and sustained degradation for up to 36 h at 1 and 10 nM^[1].
RP03707 (increasing concentrations; 24 h) potently degrades KRAS^G12D protein in GP2D, PK-59, and AGS cells, with DC₅₀ values ranging from 0.7 to 1.3 nM and high maximal degradation (82.0-96.0%)^[1].
RP03707 (increasing concentrations; 24 h) potently inhibits ERK phosphorylation in AsPC-1, AGS, GP2D, and PK-59 cells, with IC₅₀ values ranging from 0.35 to 10.6 nM^[1].
RP03707 (increasing concentrations; 72 h) potently inhibits proliferation of AsPC-1, AGS, GP2D, and PK-59 cells, with IC₅₀ values ranging from 0.19 to 4.19 nM^[1].
RP03707 (1 μM; 0-120 min) exhibits favorable metabolic stability across multiple species, with exceptionally long human plasma stability and moderate human liver clearance^[1].

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

Western Blot Analysis^[1]

Cell Line:

human pancreatic cancer AsPC-1 cells
Concentration:

5 nM (screening); 0.0025-50 nM (24 h dose-response); 1-10 nM (time-course)
Incubation Time:

24 h (dose-response); 0, 1, 3, 6, 12, 24, 36, 48, 72 h (time-course)
Result:

Induced over 90% KRAS^G12D degradation at 5 nM.
Achieved a DC₅₀ of 0.6 nM and a maximal degradation (D_max) of 89.0% in 24 h dose-response assay.
Achieved ~70% maximal degradation at 12 h, which persisted until 36 h before declining at 1 nM.
Achieved ~90% maximal degradation at 12 h, which persisted until 36 h with a slower decline through 72 h at 10 nM.

Western Blot Analysis^[1]

Cell Line:

human colon cancer GP2D cells, human pancreatic cancer PK-59 cells, human gastric cancer AGS cells
Concentration:

increasing concentrations (dose-response analysis)
Incubation Time:

24 h
Result:

Exhibited a DC₅₀ of 0.7 nM and a D_max of 93.3% in GP2D cells.
Exhibited a DC₅₀ of 0.7 nM and a D_max of 96.0% in PK-59 cells.
Exhibited a DC₅₀ of 1.3 nM and a D_max of 82.0% in AGS cells.

Cell Proliferation Assay^[1]

Cell Line:

human pancreatic cancer AsPC-1 cells, human gastric cancer AGS cells, human colon cancer GP2D cells, human pancreatic cancer PK-59 cells
Concentration:

increasing concentrations
Incubation Time:

72 h
Result:

Inhibited cell proliferation with an IC₅₀ of 4.19 nM in AsPC-1 cells.
Inhibited cell proliferation with an IC₅₀ of 1.01 nM in AGS cells.
Inhibited cell proliferation with an IC₅₀ of 0.19 nM in GP2D cells.
Inhibited cell proliferation with an IC₅₀ of 2.8 nM in PK-59 cells.

Parmacokinetics

Species	Dose	Route	T_1/2	AUC_0-t	V_ss	CL
Mice^[1]	1 mg/kg	i.v.	8.82 h	0.397 μM·h	15808 mL/kg	39 mL/min/kg
Rat^[1]	1 mg/kg	i.v.	9.63 h	0.531 μM·h	10285 mL/kg	33 mL/min/kg
Dog^[1]	1 mg/kg	i.v.	15.6 h	0.458 μM·h	15957 mL/kg	33 mL/min/kg
Cynomolgus Monkey^[1]	1 mg/kg	i.v.	12.4 h	0.836 μM·h	12748 mL/kg	19.5 mL/min/kg

In Vivo

RP03707 (0.1-1 mg/kg; i.v.; weekly; 4 weeks) administered weekly via intravenous injection induces potent dose-dependent tumor growth inhibition in PK-59 KRAS^G12D pancreatic cancer xenografts, with 98% TGI achieved at the 1 mg/kg dose^[1].
RP03707 (1-10 mg/kg; i.v.; weekly, every 2 weeks; 4 weeks) administered via intravenous injection induces dose-dependent tumor growth inhibition and regression in GP2D KRAS^G12D colorectal cancer xenografts, with 30.9% tumor regression achieved at the 10 mg/kg weekly dose^[1].
RP03707 (10 mg/kg; i.v.; single dose) achieves sustained high tumor concentrations, prolonged KRAS^G12D degradation, suppressed MAPK signaling, and increased apoptotic markers in PK-59 KRAS^G12D pancreatic cancer xenografts for up to 168 hours^[1].
RP03707 (10 mg/kg; i.v.; single dose) achieves high, sustained tumor concentrations, 95% KRAS^G12D degradation, suppressed MAPK signaling, and increased apoptotic markers in GP2D KRAS^G12D colorectal cancer xenografts for up to 168 hours^[1].

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

Animal Model:

BALB/c nude (female, 6−8 weeks old)^[1]
Dosage:

0.1 mg/kg; 0.3 mg/kg; 1 mg/kg
Administration:

i.v.; weekly; 4 weeks
Result:

Achieved 81.4% tumor growth inhibition (TGI) at day 28 with 0.1 mg/kg dose.
Achieved 93% TGI at day 28 with 0.3 mg/kg dose.
Achieved 98% TGI at day 28 with 1 mg/kg dose.
Showed no adverse effects based on body weight changes.

Animal Model:

BALB/c nude (female, 6−8 weeks old, tumor size ~500−700 mm³)^[1]
Dosage:

10 mg/kg
Administration:

i.v.; single dose
Result:

Maintained high tumor concentrations, decreasing from 1044 ng/g at 6 hours to 719 ng/g at 168 hours.
Reached and maintained high levels of KRAS^G12D protein degradation, with 87.7% degradation at 168 hours.
Kept pERK levels consistently low.
Reduced DUSP4 levels to 11% at 6 hours and maintained at 6.1% at 168 hours.

Chemical Information

CAS. Nr. 3030493-05-8
Appearance Solid
Molecular Weight 994.12
Formel C₅₅H₅₈F₃N₁₁O₄
Color Light yellow to yellow
SMILES

O=C1NC(CCN1C2=NN(C)C3=C2C=C(F)C(C4CCN(C5CC6(CCN(CC7(COC8=NC9=C(C=NC(C%10=C%11C(C#C)=C(F)C=CC%11=CC(O)=C%10)=C9F)C(N%12C[C@H]%13N[C@H](CC%13)C%12)=N8)CC7)CC6)C5)CC4)=C3)=O
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

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 100 mg/mL (100.59 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

1.0059 mL

5.0296 mL

10.0591 mL

5 mM

0.2012 mL

1.0059 mL

2.0118 mL

10 mM

0.1006 mL

0.5030 mL

1.0059 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: 10% DMSO 90% Corn Oil

Solubility: ≥ 5 mg/mL (5.03 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL Corn oil, and mix evenly.

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 (279 KB)
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)
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]. Ji X, et al. Discovery and Characterization of RP03707: A Highly Potent and Selective KRAS^G12D PROTAC. J Med Chem. 2025;68(10):10238-10254. [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	1.0059 mL	5.0296 mL	10.0591 mL	25.1479 mL
	5 mM	0.2012 mL	1.0059 mL	2.0118 mL	5.0296 mL
	10 mM	0.1006 mL	0.5030 mL	1.0059 mL	2.5148 mL
	15 mM	0.0671 mL	0.3353 mL	0.6706 mL	1.6765 mL
	20 mM	0.0503 mL	0.2515 mL	0.5030 mL	1.2574 mL
	25 mM	0.0402 mL	0.2012 mL	0.4024 mL	1.0059 mL
	30 mM	0.0335 mL	0.1677 mL	0.3353 mL	0.8383 mL
	40 mM	0.0251 mL	0.1257 mL	0.2515 mL	0.6287 mL
	50 mM	0.0201 mL	0.1006 mL	0.2012 mL	0.5030 mL
	60 mM	0.0168 mL	0.0838 mL	0.1677 mL	0.4191 mL
	80 mM	0.0126 mL	0.0629 mL	0.1257 mL	0.3143 mL
	100 mM	0.0101 mL	0.0503 mL	0.1006 mL	0.2515 mL

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RP03707

PROTAC Library

MCE Bioactive Compound Library

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle Ras Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

RP03707

PROTAC Library

MCE Bioactive Compound Library

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle Ras Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

RP03707 Related Classifications

HY-176134 Related Classifications