TMX-2172
Based on 1 Customer Validation
TMX-2172 is a selective bivalent cereblon-recruiting PROTAC-based dual CDK2 and CDK5 degrader with IC50 values of 6.5 nM and 6.8 nM, respectively. TMX-2172 shows selectivity for CDK2 and CDK5 over other cell cycle CDKs (CDK1, CDK4, and CDK6) and transcriptional CDKs (CDK7 and CDK9). TMX-2172 inhibits CDK2/CDK5 enzymatic activity, induces their proteasomal degradation, reduces ASCL1 protein levels and half-life, induces cancer cell death, and exerts antiproliferative effects. TMX-2172 can be used for the research of ovarian cancer and small cell lung cancer.
(Pink: CDK2 and CDK5 Target protein ligand; Blue: Cereblon ligand (HY-41547); Black: linker (HY-W008352)).
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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: 99.38%
- CAS 番号: 2488892-09-5
- 分子式: C41H45BrFN9O11S
- 分子量:970.82
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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
製品説明
IC50 & Target
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CDK2 6.5 nM (IC50) |
CDK5 6.8 nM (IC50) |
体外実験
TMX-2172 (6.5-33 nM) acts as a dual CDK2/CDK5 degrader, potently inhibiting CDK2 enzyme activity (IC50 6.5 nM), OVCAR8 ovarian cancer cell proliferation (IC50 33 nM), and inducing CDK2 degradation in OVCAR8 cells (DC50 33 nM), with cell death dependent on CDK2 degradation rather than CDK5 activity[1].
TMX-2172 (0.12-10 μM) efficiently degrades HiBit-tagged CDK2 in CRISPR-edited HEK293T cells, as measured by reduced normalized luminescence signals[2].
TMX-2172 (500 nM; 36 h) down-regulates CDK2 and ASCL1 protein levels in NCI-H1876 human SCLC cells, with no significant change in ASCL1 mRNA levels[3].
TMX-2172 (500 nM; 8 h) down-regulates CDK2 and ASCL1 protein and mRNA levels in 97-2 mouse SCLC cells[3].
TMX-2172 (500 nM; 4 h) decreases the half-life of ASCL1 protein in 97-2 mouse SCLC cells, with the half-life reduced from 28 to 21 minutes following treatment with 500 nM TMX-2172 for 4 hours plus cycloheximide chase[3].
TMX-2172 (250 nM; dose-dependent concentrations) selectively degrades CDK2 in Jurkat and OVCAR8 human cancer cell lines, with CDK5 degradation in OVCAR8 cells not contributing to anti-proliferative activity[4].
TMX-2172 exhibits potent inhibitory activity against CDK2/cyclin A and CDK5/p25 (IC50 = 6.5 nM and 6.8 nM, respectively), with drastically reduced potency against CDK1, CDK4, CDK6, CDK7, and CDK9[5].
TMX-2172 engages CRBN in cells with an IC50 of 46.9 nM, demonstrating good cell permeability[5].
TMX-2172 (0.05-5 μM; 6 h) induces dose-dependent CRBN-mediated degradation of CDK2 and CDK5, but not CDK1, CDK4, CDK6, CDK7, or CDK9, in Jurkat cells[5].
TMX-2172 (250 nM; 6 h) effectively degrades CDK2, CDK5, and Aurora A, and weakly degrades RSK1, JNK2, and STK33, but does not degrade CDK1, in OVCAR8 cells[5].
TMX-2172 (0.05-5 μM; 6 h) induces dose-dependent degradation of CDK2 and CDK5, but not CDK1, CDK4, CDK6, CDK7, or CDK9, in OVCAR8 cells; 5 μM is required for observable Aurora A degradation[5].
TMX-2172 (72 h) potently inhibits OVCAR8 cell growth with a GR50 of 33.1 nM, with activity driven primarily by CDK2 degradation rather than CDK5 degradation[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Jurkat cells, CRBN-null Jurkat cells
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Concentration:0.05 μM, 0.1 μM, 0.25 μM, 0.5 μM, 1 μM, 5 μM
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Incubation Time:6 h
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Result:Induced dose-dependent degradation of CDK2 and CDK5.
No degradation of CDK1, CDK4, CDK6, CDK7, or CDK9 was observed at any tested concentration.
Detected no CDK2 degradation in CRBN-null Jurkat cells treated with the same concentrations for 6 h.
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Cell Line:OVCAR8 cells
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Concentration:0.05 μM, 0.1 μM, 0.25 μM, 0.5 μM, 1 μM, 5 μM
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Incubation Time:6 h
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Result:Induced dose-dependent degradation of CDK2 and CDK5.
No degradation of CDK1, CDK4, CDK6, CDK7, or CDK9 was observed at any tested concentration.
Required a concentration of 5 μM to achieve observable degradation of Aurora A under the same conditions.
化学情報
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CAS 番号 2488892-09-5
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性状 Solid
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分子量 970.82
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分子式 C41H45BrFN9O11S
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Color Light yellow to yellow
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SMILES
O=C(C1=C(NC2=NC(NC3=CC=C(S(=O)(NCCOCCOCCOCCOCCNC4=CC=CC(C(N5C6C(NC(CC6)=O)=O)=O)=C4C5=O)=O)C=C3C)=NC=C2Br)C=CC=C1F)N
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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
体外:
DMSO : 100 mg/mL (103.01 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)
体内:
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 (2.58 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.
In Vivo Dissolution Calculator
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 (277 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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取扱説明書 (2659 KB)
参考文献
[1]. Giarolla J, et al. Targeting cyclin-dependent kinase 2 (CDK2) interactions with cyclins and Speedy 1 (Spy1) for cancer and male contraception. Future Med Chem. 2025;17(5):607-627. [Content Brief]
[2]. Teng M, et al. Exploring Ligand-Directed N-Acyl-N-alkylsulfonamide-Based Acylation Chemistry for Potential Targeted Degrader Development. ACS Med Chem Lett. 2021 Jul 21;12(8):1302-1307. [Content Brief]
[3]. Koduri V, et al. Targeting oncoproteins with a positive selection assay for protein degraders. Sci Adv. 2021 Feb 5;7(6):eabd6263. [Content Brief]
[4]. Zeng Y, et al. Inhibitors and PROTACs of CDK2: challenges and opportunities. Expert Opin Drug Discov. 2024;19(9):1125-1148. [Content Brief]
[5]. Teng M, et al. Development of CDK2 and CDK5 Dual Degrader TMX-2172. Angew Chem Int Ed Engl. 2020;59(33):13865-13870. [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 | 1.0301 mL | 5.1503 mL | 10.3006 mL | 25.7514 mL |
| 5 mM | 0.2060 mL | 1.0301 mL | 2.0601 mL | 5.1503 mL | |
| 10 mM | 0.1030 mL | 0.5150 mL | 1.0301 mL | 2.5751 mL | |
| 15 mM | 0.0687 mL | 0.3434 mL | 0.6867 mL | 1.7168 mL | |
| 20 mM | 0.0515 mL | 0.2575 mL | 0.5150 mL | 1.2876 mL | |
| 25 mM | 0.0412 mL | 0.2060 mL | 0.4120 mL | 1.0301 mL | |
| 30 mM | 0.0343 mL | 0.1717 mL | 0.3434 mL | 0.8584 mL | |
| 40 mM | 0.0258 mL | 0.1288 mL | 0.2575 mL | 0.6438 mL | |
| 50 mM | 0.0206 mL | 0.1030 mL | 0.2060 mL | 0.5150 mL | |
| 60 mM | 0.0172 mL | 0.0858 mL | 0.1717 mL | 0.4292 mL | |
| 80 mM | 0.0129 mL | 0.0644 mL | 0.1288 mL | 0.3219 mL | |
| 100 mM | 0.0103 mL | 0.0515 mL | 0.1030 mL | 0.2575 mL |
TMX-2172 関連分類
HY-155218 関連分類
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