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)).
For research use only. We do not sell to patients.
- Purity : 99.38%
- CAS No.: 2488892-09-5
- Formula: C41H45BrFN9O11S
- Molecular Weight:970.82
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Storage: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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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
IC50 & Target
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CDK2 6.5 nM (IC50) |
CDK5 6.8 nM (IC50) |
In Vitro
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. Further protocols information, click here.
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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.
Chemical Information
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CAS No. 2488892-09-5
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Appearance Solid
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Molecular Weight 970.82
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Formula 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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
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.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Flow cytometric DNA-content cell-cycle staining
Flow cytometric DNA-content cell-cycle staining measures the fluorescence intensity of DNA-bound fluorochromes in single cells or nuclei to estimate DNA content distributions, allowing assignment of populations to G0/G1, S, and G2/M phases by DNA histogram deconvolution. Propidium iodide (PI) intercalates into DNA, and PI fluorescence is proportional to cellular DNA content when staining is performed under conditions that make DNA accessible and minimize non-DNA signal. Cells with G2/M DNA content are expected to show approximately twice the fluorescence intensity of G0/G1 cells, while S-phase cells occupy intermediate fluorescence values. PI-based DNA-content analysis can also detect cells with fractional DNA content, often reported as sub-G1, when DNA fragmentation and extraction during staining reduce retained DNA signal in apoptotic cells. DAPI is an alternative DNA fluorochrome for univariate DNA-content analysis, while bivariate approaches combining DNA content with proliferation
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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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BrdU Incorporation Assay
Bromodeoxyuridine (BrdU) incorporation assay is based on the principle that BrdU, a thymidine analog, is incorporated into newly synthesized DNA during the S phase of the cell cycle, thereby serving as a marker of DNA replication and cellular proliferation. Incorporated BrdU can be detected using anti-BrdU antibodies following DNA denaturation, enabling visualization or quantification of proliferating cells through immunochemical detection methods such as immunofluorescence or immunohistochemistry.
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Protocol for Pharmacokinetic Study
Pharmacokinetic studies quantify how an organism handles a drug over time through absorption, distribution, metabolism, and excretion, and the core experimental readout is the concentration-time profile of parent drug and, when relevant, metabolites in biological matrices such as plasma, whole blood, urine, bile, or tissue. Pharmacokinetic analysis links dose, route, exposure, clearance, half-life, distribution, bioavailability, and systemic exposure to drug efficacy and toxicity hypotheses rather than measuring a signaling pathway directly. The literature links pharmacokinetics to drug-development phenotypes by showing that drug metabolism and pharmacokinetics influence compound progression, exposure-response interpretation, safety margins, dosing strategy, and failure risk during discovery and development. DMPK science contributes to compound optimization by integrating physicochemical properties, in vitro metabolism, transporter behavior, in vivo exposure, and pharmacodynamic contex
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Protocol for Cell Cycle
Cell-cycle analysis by flow cytometry measures DNA content in single cells to estimate the fraction of cells in G0/G1, S, and G2/M phases. Propidium iodide intercalates into DNA, and after RNA removal with RNase, fluorescence intensity reflects cellular DNA content: 2N cells are assigned to G0/G1, cells between 2N and 4N to S phase, and 4N cells to G2/M. DNA-content analysis alone cannot reliably separate G0 from G1 or G2 from M. Ki-67 can distinguish quiescent G0 cells from cycling cells, EdU or BrdU incorporation marks active DNA synthesis in S phase, and phospho-histone H3 staining identifies mitotic cells within the 4N population.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
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Data Sheet (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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Handling Instructions (2659 KB)
References
[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 Related Classifications
HY-155218 Related Classifications
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