YDR1
Based on 1 Customer Validation
YDR1 is an orally active and selective SMARCA2 PROTAC degrader. YDR1 selectively inhibits the growth of various cancer cells and suppresses tumor growth in mouse xenograft models. YDR1 can be used for the research of SMARCA4-mutant lung cancer.
(Pink: SMARCA2 ligand (HY-44012B); Blue: Cereblon ligand (HY-W087383); Black: linker (HY-168218)).
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
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: 98.06%
- CAS 番号: 2951015-31-7
- 分子式: C44H49FN10O5
- 分子量:816.92
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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
生物活性
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SMARCA2 |
YDR1 (0.001-10 μM; 24-48 h) potently and selectively degrades SMARCA2 over SMARCA4 in SMARCA4-WT H1792 human lung cancer cells, with a DC50 of 69 nM at 24 h and 60 nM at 48 h[1].
YDR1 (0.001-10 μM; 48 h) potently degrades SMARCA2 in SMARCA4 mutant H322, HCC515, H2030, and H2126 human lung cancer cells, with DC50 values ranging from 1.2 nM to 12.7 nM after 48 h incubation[1].
YDR1 (0.001-10 μM; 10 days) selectively inhibits the clonogenic growth of SMARCA4 mutant H1568 and H1693 human lung cancer cells over SMARCA4-WT HCC44 and H2122 cells, with an average IC50 of 78 nM in mutant cells[1].
YDR1 (100 nM; 48 h) shows remarkable selectivity for SMARCA2 degradation in SMARCA4-WT H1792 human lung cancer cells, with SMARCA2 being the only significantly downregulated protein after 48 h treatment with 100 nM YDR1[1].
YDR1 synergizes with Sotorasib (HY-114277) to inhibit the growth of SMARCA4 and KRASG12C comutant H2030 human lung cancer cells, as evidenced by Bliss synergy scores of 12.98 and 24.3 from independent assays[1].
YDR1 (10 μM; 60 min) shows slow clearance in both human and mouse liver microsomes, with a T1/2 of 58 min in human microsomes and 59 min in mouse microsomes, and forms three low-abundance metabolites in mouse liver microsomes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SMARCA4-WT H1792 human lung cancer cells
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Concentration:0, 0.001, 0.01, 0.1, 1and 10 μM
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Incubation Time:24 h; 48 h
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Result:Degraded SMARCA2 with a DC50 of 69 nM and a maximal degradation (Dmax) of 87% after 24 h incubation.
Degraded SMARCA4 with a DC50 of 135 nM and Dmax of 79% after 24 h incubation.
Degraded SMARCA2 with a DC50 of 60 nM and Dmax of 94% after 48 h incubation.
Degraded SMARCA4 with a DC50 of 381 nM and Dmax of 69% after 48 h incubation.
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Cell Line:SMARCA4 mutant H322, HCC515, H2030, and H2126 human lung cancer cells
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Concentration:0, 0.001, 0.01, 0.1, 1and 10 μM
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Incubation Time:48 h
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Result:Degraded SMARCA2 in H322 cells with a DC50 of 6.4 nM and Dmax of 99.2%.
Degraded SMARCA2 in HCC515 cells with a DC50 of 10.6 nM and Dmax of 99.4%.
Degraded SMARCA2 in H2030 cells with a DC50 of 12.7 nM and Dmax of 98.7%.
Degraded SMARCA2 in H2126 cells with a DC50 of 1.2 nM and Dmax of 99.6%.
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Cell Line:SMARCA4 mutant H1568, H1693 and SMARCA4-WT HCC44, H2122 human lung cancer cells
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Concentration:0.001, 0.01, 0.1, 1and 10 μM
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Incubation Time:10 days
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Result:Caused dose-dependent inhibition of clonogenic growth in SMARCA4 mutant cells, with an average IC50 of 78 nM.
Had minimal impact on SMARCA4-WT cells, with an average IC50 of 10 μM, resulting in a 128-fold selectivity for SMARCA4 mutant cells over WT cells.
YDR1 (10-80 mg/kg; p.o.; daily; 4 days) induces dose-dependent degradation of SMARCA2 in H1568 xenograft tumors, achieving maximum 87% degradation at 80 mg/kg oral dosing for 4 days[1].
YDR1 (40 mg/kg; p.o.; daily; 13 days) exhibits moderate antitumor activity in H1568 xenograft tumors, achieving 27.6% tumor growth inhibition at 40 mg/kg oral dosing for 13 days, while reducing SMARCA2 levels by ~50%[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6[1]
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Dosage:5 mg/kg; 10 mg/kg; 20 mg/kg; 40 mg/kg; 80 mg/kg
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Administration:p.o.; daily; 3 days
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Result:Reached plasma concentrations ranging from ~100 nM (5 mg/kg group) to 1.88 μM (80 mg/kg group).
Induced dose-dependent degradation of SMARCA2 protein in spleen, with 70% degradation observed at 80 mg/kg dose.
Caused only modest degradation of SMARCA4 relative to SMARCA2.
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Animal Model:CrbnI391V (genetically modified to humanize cereblon binding)[1]
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Dosage:10 mg/kg; 20 mg/kg; 40 mg/kg; 80 mg/kg
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Administration:p.o.; daily; 3 days
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Result:Reached plasma concentrations ranging from 1 μM (10 mg/kg group) to 2.45 μM (80 mg/kg group).
Induced dose-dependent degradation of SMARCA2 protein in spleen, with 81% degradation observed at 80 mg/kg dose.
Achieved 11-38% greater SMARCA2 degradation at all doses compared to C57BL/6 mice.
Caused only modest degradation of SMARCA4 relative to SMARCA2.
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Animal Model:Female athymic nude (6-8 weeks of age) were subcutaneously injected in the flanks with H1568 cells (2 × 106 cells/mouse) that had been trypsinized and resuspended in 1× PBS, mixed with a 1:1 mix of Matrigel in a final volume of 200 μL. Mice were randomized to control and treatment groups once the average tumor volume of H1568 xenograft reached 60 mm3[1]
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Dosage:10 mg/kg; 20 mg/kg; 40 mg/kg; 80 mg/kg
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Administration:p.o.; daily; 4 days or 13 days
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Result:Reached plasma concentrations ranging from ~0.5 μM (10 mg/kg group) to ~2 μM (80 mg/kg group).
Induced dose-dependent degradation of SMARCA2 protein in tumors, with 87% degradation observed at 80 mg/kg dose.
Confirmed robust reduction in nuclear SMARCA2 signal in tumors from mice treated with 80 mg/kg via immunohistochemistry.
When YDR1 was administered orally at 40 mg/kg once daily for 13 days, it inhibited tumor growth with a tumor growth inhibition (TGI) of 27.6% compared to vehicle control, reduced SMARCA2 protein levels in tumors to approximately 50% of vehicle control levels, and was well tolerated with no change in mouse body weight.
化学情報
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CAS 番号 2951015-31-7
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性状 Solid
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分子量 816.92
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分子式 C44H49FN10O5
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Color Light yellow to yellow
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SMILES
O=C(N(C1CCC(NC1=O)=O)C2=O)C3=C2C=CC(N4CCN(CC5CCN(C6=C(F)C=C(CN7CCN(C8=C(N)N=NC(C9=C(O)C=CC=C9)=C8)CC7)C=C6)CC5)CC4)=C3
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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 (122.41 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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (3.06 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
純度とドキュメンテーション
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データシート (280 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
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- 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
[1]. Kotagiri S, et al. Discovery of Novel, Potent, and Orally Bioavailable SMARCA2 Proteolysis-Targeting Chimeras with Synergistic Antitumor Activity in Combination with Kirsten Rat Sarcoma Viral Oncogene Homologue G12C Inhibitors. Journal of medicinal chemistry. 2025 May 08;68(9):9202-9219. [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 | 1.2241 mL | 6.1206 mL | 12.2411 mL | 30.6028 mL |
| 5 mM | 0.2448 mL | 1.2241 mL | 2.4482 mL | 6.1206 mL | |
| 10 mM | 0.1224 mL | 0.6121 mL | 1.2241 mL | 3.0603 mL | |
| 15 mM | 0.0816 mL | 0.4080 mL | 0.8161 mL | 2.0402 mL | |
| 20 mM | 0.0612 mL | 0.3060 mL | 0.6121 mL | 1.5301 mL | |
| 25 mM | 0.0490 mL | 0.2448 mL | 0.4896 mL | 1.2241 mL | |
| 30 mM | 0.0408 mL | 0.2040 mL | 0.4080 mL | 1.0201 mL | |
| 40 mM | 0.0306 mL | 0.1530 mL | 0.3060 mL | 0.7651 mL | |
| 50 mM | 0.0245 mL | 0.1224 mL | 0.2448 mL | 0.6121 mL | |
| 60 mM | 0.0204 mL | 0.1020 mL | 0.2040 mL | 0.5100 mL | |
| 80 mM | 0.0153 mL | 0.0765 mL | 0.1530 mL | 0.3825 mL | |
| 100 mM | 0.0122 mL | 0.0612 mL | 0.1224 mL | 0.3060 mL |
YDR1 関連分類
HY-168215 関連分類
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