RP03707
Based on 1 Customer Validation
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)).
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度: 98.00%
- CAS 番号: 3030493-05-8
- 分子式: C55H58F3N11O4
- 分子量:994.12
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保管条件:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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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生物活性
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化学情報
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溶剤 & 溶解度
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
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生物活性
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.
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Cell Line:human pancreatic cancer AsPC-1 cells
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Concentration:5 nM (screening); 0.0025-50 nM (24 h dose-response); 1-10 nM (time-course)
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Incubation Time:24 h (dose-response); 0, 1, 3, 6, 12, 24, 36, 48, 72 h (time-course)
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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.
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Cell Line:human colon cancer GP2D cells, human pancreatic cancer PK-59 cells, human gastric cancer AGS cells
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Concentration:increasing concentrations (dose-response analysis)
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Incubation Time:24 h
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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.
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Cell Line:human pancreatic cancer AsPC-1 cells, human gastric cancer AGS cells, human colon cancer GP2D cells, human pancreatic cancer PK-59 cells
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Concentration:increasing concentrations
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Incubation Time:72 h
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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.
| Species | Dose | Route | T1/2 | AUC0-t | Vss | CL |
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| 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 |
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.
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Animal Model:BALB/c nude (female, 6−8 weeks old)[1]
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Dosage:0.1 mg/kg; 0.3 mg/kg; 1 mg/kg
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Administration:i.v.; weekly; 4 weeks
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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.
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Animal Model:BALB/c nude (female, 6−8 weeks old, tumor size ~500−700 mm3)[1]
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Dosage:10 mg/kg
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Administration:i.v.; single dose
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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.
化学情報
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CAS 番号 3030493-05-8
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性状 Solid
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分子量 994.12
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分子式 C55H58F3N11O4
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Color Light yellow to yellow
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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
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
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)
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.
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.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
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.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%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
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
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.
純度とドキュメンテーション
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データシート (279 KB)
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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)
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取扱説明書 (2659 KB)
参考文献
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 |
RP03707 関連分類
HY-176134 関連分類
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