2. PROTAC MAPK/ERK Pathway GPCR/G Protein
  3. PROTACs Ras
  4. RP03707

RP03707 is a PROTAC degrader of KRASG12D. RP03707 forms a ternary complex with KRASG12D and the CRBN E3 ligase, promoting the ubiquitination and proteasomal degradation of KRASG12D. RP03707 inhibits the growth of KRASG12D-positive tumor cells.
(Pink: KRas G12D ligand (HY-134813); Blue: Cereblon ligand (HY-49385); Black: linker (HY-176137)).

For research use only. We do not sell to patients.

RP03707

RP03707 Chemical Structure

CAS No. : 3030493-05-8

Size Price Stock Quantity
5 mg In-stock
10 mg In-stock
25 mg In-stock
50 mg   Get quote  
100 mg   Get quote  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 1 Customer Validation

RP03707 Related Antibodies

Top Publications Citing Use of Products

View All PROTACs Isoform Specific Products:

View All Isoforms
von Hippel-Lindau (VHL) Cereblon MDM2 cIAP1

View All Ras Isoform Specific Products:

View All Isoforms
K-Ras H-Ras N-Ras Ras

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

RP03707 is a PROTAC degrader of KRASG12D. RP03707 forms a ternary complex with KRASG12D and the CRBN E3 ligase, promoting the ubiquitination and proteasomal degradation of KRASG12D. RP03707 inhibits the growth of KRASG12D-positive tumor cells[1]. (Pink: KRas G12D ligand (HY-134813); Blue: Cereblon ligand (HY-49385); Black: linker (HY-176137)).

In Vitro

RP03707 (0.0025-50 nM; 0-72 h) potently and rapidly degrades KRASG12D 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 KRASG12D 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.

RP03707 Related Antibodies

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% KRASG12D degradation at 5 nM.
Achieved a DC50 of 0.6 nM and a maximal degradation (Dmax) 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 Dmax of 93.3% in GP2D cells.
Exhibited a DC50 of 0.7 nM and a Dmax of 96.0% in PK-59 cells.
Exhibited a DC50 of 1.3 nM and a Dmax 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 T1/2 AUC0-t Vss 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 KRASG12D 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 KRASG12D 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 KRASG12D degradation, suppressed MAPK signaling, and increased apoptotic markers in PK-59 KRASG12D pancreatic cancer xenografts for up to 168 hours[1].
RP03707 (10 mg/kg; i.v.; single dose) achieves high, sustained tumor concentrations, 95% KRASG12D degradation, suppressed MAPK signaling, and increased apoptotic markers in GP2D KRASG12D 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 KRASG12D 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.
Molecular Weight

994.12

Formula

C55H58F3N11O4
CAS No.
Appearance

Solid

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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
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)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.0059 mL 5.0296 mL 10.0591 mL
5 mM 0.2012 mL 1.0059 mL 2.0118 mL
View the Complete Stock Solution Preparation Table

* 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.

  • Molarity Calculator

  • Dilution Calculator

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

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

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

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

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
References

Complete Stock Solution Preparation Table

* 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.

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
  • No file chosen (Maximum size is: 1024 Kb)
  • If you have published this work, please enter the PubMed ID.
  • Your name will appear on the site.

RP03707 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

RP037073030493-05-8RP 03707RP-03707PROTACsRasextracellular signal-regulated kinaseKRASG12D-driven tumorsCRBNMAPK signaling pathwayE3 ligasemouse cell-derived xenograft modelsproteasomal degradationAsPC-1 cellsKRASG12DubiquitinationInhibitorinhibitorinhibit

Your Recently Viewed Products:

Inquiry Online

Your information is safe with us. * Required Fields.

Product Name

  

Requested Quantity *

Applicant Name *

 

Salutation

Email Address *

 

Phone Number *

Department

 

Organization Name *

City

State

Country or Region *

      

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
RP03707
Cat. No.:
HY-176134
Quantity:
MCE Japan Authorized Agent:

Customer Review

Thank You for Your Feedback!

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

Product Name

  

Lot #

Applicant Name *

 

Email Address *

Phone Number

 

Department *

Organization Name *

 

Country or Region *

Remarks

SAFETY DATA SHEET (SDS)

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)

Request for HNMR Report

We have received your request and will respond to you as soon as possible.