HRS-4642
Based on 1 Customer Validation
HRS-4642 is a high affinity, selective, long-acting, and non-covalent KRASG12D inhibitor with a Kd value of 0.083 nM. HRS-4642 inhibits the binding of KRASG12D to SOS1 or RAF1, thereby blocking the downstream MEK-ERK signaling pathway. HRS-4642 promotes Apoptosis. HRS-4642 alone or combined with Carfilzomib (HY-10455) effectively shapes the tumor microenvironment. HRS-4642 has an anti-cancer effect on pancreatic and colorectal cancers carrying the KRASG12D mutation[1][2][3].
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- Purity: 99.74%
- CAS No.: 2836263-09-1
- 화학식: C34H35F3N6O3
- 분자량:632.68
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보관:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
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Biological Activity
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KRas G12D 0.083 nM (Kd) |
HRS-4642 selectively binds to *KRAS*G12D[2].
HRS-4642 inhibits KRASG12D binding to SOS1 or RAF1, blocking the downstream MEK-ERK signaling pathway[2].
HRS-4642 specifically inhibits the proliferation of *KRAS*G12D mutant human cell lines[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
HRS-4642 (2.5-15 mg/kg; i.v.; once a week) inhibits tumor growth in in BALB/c nude mice bearing KRAS G12D-mutant AsPC-1 (pancreatic cancer) and GP2d (colorectal cancer) tumors[3].
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 mice bearing KRAS G12D-mutant AsPC-1 (human pancreatic cancer) or GP2d (human colorectal cancer) tumors[3]
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Dosage:2.5 mg/kg; 3.75 mg/kg; 7.5 mg/kg; 15 mg/kg
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Administration:Intravenous injection; once a week
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Result:Completely eradicated tumors at doses of 7.5 or 15 mg/kg.
Exhibited an excellent safety profile, as indicated by the steady body weight of the mice during treatment.
Showed inhibition of p-ERK in mice.
Showed potent proliferation inhibition and apoptosis promotion effects.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2836263-09-1
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Appearance Solid
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분자량 632.68
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화학식 C34H35F3N6O3
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Color White to off-white
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SMILES
OC(C=C1C2=C(F)C(N=C(OC[C@@]3(CCC4)N4C[C@H](F)C3)N=C5N(C[C@@H]6N[C@H]7CC6)[C@@H]7CO8)=C5C8=N2)=CC9=C1C(CC)=C(F)C=C9
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
DMSO : ≥ 100 mg/mL (158.06 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5 mg/mL (7.90 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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.
순도&문서
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Data Sheet (281 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
References
[1]. Zhou C, et al. Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer. Cancer Cell. 2024 Jul 8;42(7):1286-1300.e8. [Content Brief]
[2]. Leng Q, et al. HRS-4642 combined with nimotuzumab in the treatment of recurrent or metastatic pancreatic ductal adenocarcinoma: study protocol of a single-arm, prospective phase Ib/II trial. Front Pharmacol. 2025;16:1562481. Published 2025 Jul 4. [Content Brief]
[3]. Li Y, et al. New exploration of KRASG12D inhibitors and the mechanisms of resistance. Exp Hematol Oncol. 2025;14(1):39. Published 2025 Mar 17. [Content Brief]
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 |
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| DMSO | 1 mM | 1.5806 mL | 7.9029 mL | 15.8058 mL | 39.5144 mL |
| 5 mM | 0.3161 mL | 1.5806 mL | 3.1612 mL | 7.9029 mL | |
| 10 mM | 0.1581 mL | 0.7903 mL | 1.5806 mL | 3.9514 mL | |
| 15 mM | 0.1054 mL | 0.5269 mL | 1.0537 mL | 2.6343 mL | |
| 20 mM | 0.0790 mL | 0.3951 mL | 0.7903 mL | 1.9757 mL | |
| 25 mM | 0.0632 mL | 0.3161 mL | 0.6322 mL | 1.5806 mL | |
| 30 mM | 0.0527 mL | 0.2634 mL | 0.5269 mL | 1.3171 mL | |
| 40 mM | 0.0395 mL | 0.1976 mL | 0.3951 mL | 0.9879 mL | |
| 50 mM | 0.0316 mL | 0.1581 mL | 0.3161 mL | 0.7903 mL | |
| 60 mM | 0.0263 mL | 0.1317 mL | 0.2634 mL | 0.6586 mL | |
| 80 mM | 0.0198 mL | 0.0988 mL | 0.1976 mL | 0.4939 mL | |
| 100 mM | 0.0158 mL | 0.0790 mL | 0.1581 mL | 0.3951 mL |
HRS-4642 Related Classifications
HY-159127 Related Classifications
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