| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| ln Vitro |
RP03707 (0.0025-50 nM; 0-72 hours) can effectively and rapidly degrade KRASG12D protein in AsPC-1 cells with a DC50 of 0.6 nM, and can sustain degradation for up to 36 hours at concentrations of 1 nM and 10 nM [1]. RP03707 (incremental concentration; 24 hours) can effectively degrade KRASG12D protein in GP2D, PK-59 and AGS cells with a DC50 value ranging from 0.7 to 1.3 nM and a maximum degradation rate of 82.0-96.0% [1]. RP03707 (incremental concentration; 24 hours) can effectively inhibit ERK phosphorylation in AsPC-1, AGS, GP2D and PK-59 cells with an IC50 value ranging from 0.35 to 10.6 nM [1]. RP03707 (concentration escalation; 72 hours) effectively inhibited the 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) showed good metabolic stability in multiple species, with extremely long human plasma stability and moderate human liver clearance [1].
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| ln Vivo |
Once-weekly intravenous injection of RP03707 (0.1-1 mg/kg; intravenous injection; once a week; for 4 weeks) effectively inhibited the growth of PK-59 KRASG12D pancreatic cancer xenografts in a dose-dependent manner, with a tumor growth inhibition rate (TGI) of 98% at a dose of 1 mg/kg[1]. Once-weekly or bi-weekly intravenous injection of RP03707 (1-10 mg/kg; intravenous injection; once a week, bi-weekly; for 4 weeks) effectively inhibited the growth of GP2D KRASG12D colorectal cancer xenografts and caused them to regress in a dose-dependent manner, with a tumor regression rate of 30.9% at a dose of 10 mg/kg once a week[1]. RP03707 (10 mg/kg; intravenous injection; single dose) maintained a high tumor concentration for up to 168 hours in PK-59 KRASG12D pancreatic cancer xenografts, prolonging KRASG12D degradation, inhibiting the MAPK signaling pathway, and increasing apoptosis markers [1]. RP03707 (10 mg/kg; intravenous injection; single dose) maintained a high tumor concentration for up to 168 hours in GP2D KRASG12D colorectal cancer xenografts, with 95% KRASG12D degradation, inhibiting the MAPK signaling pathway, and increasing apoptosis markers [1].
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| Cell Assay |
Western Blot Analysis [1]
Cell Types: Human pancreatic cancer AsPC-1 cells Tested Concentrations: 5 nM (screening); 0.0025-50 nM (24-hour dose-response); 1-10 nM (time course) Incubation Duration: 24 hours (dose-response); 0, 1, 3, 6, 12, 24, 36, 48, 72 hours (time course) Experimental Results: KRASG12D degradation was induced by more than 90% at a concentration of 5 nM. In the 24-hour dose-response experiment, DC50 reached 0.6 nM, and the maximum degradation rate (Dmax) reached 89.0%. At a concentration of 1 nM, the maximum degradation rate of about 70% was reached at 12 hours and continued to decline after 36 hours. At a concentration of 10 nM, the maximum degradation rate of approximately 90% was reached after 12 hours and continued until 36 hours, after which it began to decline slowly until 72 hours. Western Blot Analysis [1] Cell Types: Human colon cancer GP2D cells, human pancreatic cancer PK-59 cells, human gastric cancer AGS cells Tested Concentrations: Incremental Concentration (Dose-Response Analysis) Incubation Duration: 24 hours Experimental Results: In GP2D cells, DC50 was 0.7 nM and Dmax was 93.3%. In PK-59 cells, DC50 was 0.7 nM and Dmax was 96.0%. In AGS cells, DC50 was 1.3 nM and Dmax was 82.0%. |
| Animal Protocol |
Animal/Disease Models:BALB/c nude mice (female, 6-8 weeks old) [1]
Doses: 0.1 mg/kg; 0.3 mg/kg; 1 mg/kg Route of Administration: Intravenous injection; once a week; for 4 weeks Experimental Results: The tumor growth inhibition rate (TGI) reached 81.4% in the 0.1 mg/kg dose group on day 28. The TGI reached 93% in the 0.3 mg/kg dose group on day 28. The TGI reached 98% in the 1 mg/kg dose group on day 28. No adverse reactions were observed based on body weight changes. Animal/Disease Models:BALB/c nude mice (female, 6-8 weeks old, tumor size approximately 500-700 mm3) [1] Doses: 10 mg/kg Route of Administration: Intravenous injection; single dose Experimental Results: High tumor concentrations were maintained, decreasing from 1044 ng/g at 6 hours to 719 ng/g at 168 hours. High KRASG12D protein degradation levels were achieved and maintained, with a degradation rate of 87.7% at 168 hours. pERK levels remained consistently low. DUSP4 levels decreased to 11% at 6 hours and remained at 6.1% at 168 hours. |
| References |
| Molecular Formula |
C55H58F3N11O4
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|---|---|
| Molecular Weight |
994.12
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| CAS # |
3030493-05-8
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| Appearance |
Light yellow to yellow solid
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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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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~100.59 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (5.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you canAdd 100 μL of DMSO stock solution (50.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 | |
| 10 mM | 0.1006 mL | 0.5030 mL | 1.0059 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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