TL12-186
Based on 1 publication(s) in Google Scholar
TL12-186 is a multi-kinase PROTAC degrader. TL12-186 recruits the CRBN E3 ubiquitin ligase to target and degrade a variety of distinct kinases, including FLT3, BTK, AURKA, PTK2B, and multiple cyclin-dependent kinases (CDKs). TL12-186 can be used in leukemia-related research.
(Pink: CDK and Btk and FLT3 and Aurora Kinase and ULK and Itk and TEC ligand (HY-169396); Blue: E3 ligase ligand; Black: linker).
For research use only. We do not sell to patients.
- Purity: 99.23%
- CAS No.: 2250025-88-6
- Formula: C44H51ClN10O9S
- Molecular Weight:931.46
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Storage:
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture and light)
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
- Purity & Documentation
- References
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) TL12-186
MoreAll PROTACs Isoforms
MoreAll Aurora Kinase Isoforms
More
Biological Activity
Description
IC50 & Target
[1]|
Aurora A 1.61 nM (IC50) |
cdk2/cyclin A 73.0 nM (IC50) |
CDK7 19.1 nM (IC50) |
CDK9 55.8 nM (IC50) |
JAK2 1.93 nM (IC50) |
Cereblon |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | IC50 |
2.3 μM
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Inhibition of NanoBRET tracer K-10 binding to HiBiT-tagged CDK2 in unsynchronized CDK2-HiBiT HEK293 cells measured via NanoBRET target engagement assay after 2 hours of incubation.
Inhibition of NanoBRET tracer K-10 binding to HiBiT-tagged CDK2 in unsynchronized CDK2-HiBiT HEK293 cells measured via NanoBRET target engagement assay after 2 hours of incubation.
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33190579 |
| HEK293 | IC50 |
2.5 μM
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Inhibition of NanoBRET tracer K-10 binding to HiBiT-tagged CDK2 in G1-arrested CDK2-HiBiT HEK293 cells measured via NanoBRET target engagement assay after 2 hours of incubation.
Inhibition of NanoBRET tracer K-10 binding to HiBiT-tagged CDK2 in G1-arrested CDK2-HiBiT HEK293 cells measured via NanoBRET target engagement assay after 2 hours of incubation.
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33190579 |
| HEK293 | IC50 |
2.0 μM
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Inhibition of NanoBRET tracer K-10 binding to HiBiT-tagged CDK2 in S phase-arrested CDK2-HiBiT HEK293 cells measured via NanoBRET target engagement assay after 2 hours of incubation.
Inhibition of NanoBRET tracer K-10 binding to HiBiT-tagged CDK2 in S phase-arrested CDK2-HiBiT HEK293 cells measured via NanoBRET target engagement assay after 2 hours of incubation.
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33190579 |
| HEK293 | EC50 |
16 nM
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Induction of endogenous CDK12 ubiquitination in HEK293 cells measured by NanoBRET ubiquitination assay following 3 h incubation with TL12-186.
Induction of endogenous CDK12 ubiquitination in HEK293 cells measured by NanoBRET ubiquitination assay following 3 h incubation with TL12-186.
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35101445 |
| HEK293 | EC50 |
7 nM
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Induction of endogenous CDK13 ubiquitination in HEK293 cells measured by NanoBRET ubiquitination assay following 3 h incubation with TL12-186.
Induction of endogenous CDK13 ubiquitination in HEK293 cells measured by NanoBRET ubiquitination assay following 3 h incubation with TL12-186.
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35101445 |
| HEK293 | EC50 |
297 nM
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Induction of endogenous CDK9 ubiquitination in HEK293 cells measured by NanoBRET ubiquitination assay following 3 h incubation with TL12-186.
Induction of endogenous CDK9 ubiquitination in HEK293 cells measured by NanoBRET ubiquitination assay following 3 h incubation with TL12-186.
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35101445 |
| HEK293 | EC50 |
428 nM
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Induction of endogenous CDK7 ubiquitination in HEK293 cells measured by NanoBRET ubiquitination assay following 3 h incubation with TL12-186.
Induction of endogenous CDK7 ubiquitination in HEK293 cells measured by NanoBRET ubiquitination assay following 3 h incubation with TL12-186.
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35101445 |
| HEK293 | EC50 |
888 nM
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Induction of endogenous CDK8 ubiquitination in HEK293 cells measured by NanoBRET ubiquitination assay following 3 h incubation with TL12-186.
Induction of endogenous CDK8 ubiquitination in HEK293 cells measured by NanoBRET ubiquitination assay following 3 h incubation with TL12-186.
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35101445 |
In Vitro
TL12-186 (up to 10 μM; 2 days) significantly inhibits cell proliferation in MOLM-14 and MOLT-4 cells, with stronger inhibitory effects in WT cells than in CRBN-/- cells[1].
TL12-186 (10 nM-10 μM; 4 h) inhibits STAT1 phosphorylation and does not degrade JAK1/JAK2 in MOLT-4 cells with or without the addition of IFN-γ (HY-P7025)[1].
TL12-186 (100 nM-1 μM; 4 h) induces the degradation of FLT3, BTK, ITK, WEE1, AURKA, and PTK2B proteins in MOLM-14 and MOLT-4 cells[1].
TL12-186 potently binds to the purified human CRBN-DDB1 complex, with an IC50 of 12 nM[1].
TL12-186 (1 μM; 6-24 h) induces the degradation of 16 distinct CDK family members in HEK293 (HiBiT-CDK) cells[2].
TL12-186 (12 nM-1 μM; 24 h) induces CDK2 degradation in a concentration-dependent manner in asynchronous or G1 phase-arrested HEK293 cells[2].
TL12-186 (1 nM-10 μM; 3-5 h) induces ubiquitination of endogenous CDK7, CDK8, CDK9, CDK12, and CDK13 in HEK293 cells, and triggers ubiquitination of wild-type CDK2, CDK5, CDK9 and their corresponding mutants (K56R, K6R, K88R) [3].\n
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MOLM-14, MOLT-4
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Concentration:100 nM, 1 μM
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Incubation Time:4 h
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Result:Induced the protein degradation of multiple kinases, including PTK2B, AURKA, BTK, FLT3, ITK, and WEE1.
Chemical Information
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CAS No. 2250025-88-6
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Appearance Solid
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Molecular Weight 931.46
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Formula C44H51ClN10O9S
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Color Light yellow to yellow
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SMILES
O=C(NCCOCCOCCN1CCN(C2=CC=C(NC3=NC=C(Cl)C(NC4=CC=CC=C4S(=O)(C(C)C)=O)=N3)C=C2)CC1)CNC5=CC=CC(C(N6C(CC7)C(NC7=O)=O)=O)=C5C6=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture and light)
Publications (1)
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Journal Impact Factor
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Most Recent
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Cell Chem Biol
2022 Oct 20;29(10):1470-1481.e31. PMID: 36070758
Solvent & Solubility
In Vitro:
DMSO : 200 mg/mL (214.72 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, 2 years; -20°C, 1 year (sealed storage, away from moisture and light). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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, 2 years; -20°C, 1 year (sealed storage, away from moisture and light). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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: ≥ 5 mg/mL (5.37 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 5 mg/mL (5.37 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 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
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. * In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture and light)
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.
Purity & Documentation
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Data Sheet (273 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
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, 2 years; -20°C, 1 year (sealed storage, away from moisture and light). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.0736 mL | 5.3679 mL | 10.7358 mL | 26.8396 mL |
| 5 mM | 0.2147 mL | 1.0736 mL | 2.1472 mL | 5.3679 mL | |
| 10 mM | 0.1074 mL | 0.5368 mL | 1.0736 mL | 2.6840 mL | |
| 15 mM | 0.0716 mL | 0.3579 mL | 0.7157 mL | 1.7893 mL | |
| 20 mM | 0.0537 mL | 0.2684 mL | 0.5368 mL | 1.3420 mL | |
| 25 mM | 0.0429 mL | 0.2147 mL | 0.4294 mL | 1.0736 mL | |
| 30 mM | 0.0358 mL | 0.1789 mL | 0.3579 mL | 0.8947 mL | |
| 40 mM | 0.0268 mL | 0.1342 mL | 0.2684 mL | 0.6710 mL | |
| 50 mM | 0.0215 mL | 0.1074 mL | 0.2147 mL | 0.5368 mL | |
| 60 mM | 0.0179 mL | 0.0895 mL | 0.1789 mL | 0.4473 mL | |
| 80 mM | 0.0134 mL | 0.0671 mL | 0.1342 mL | 0.3355 mL | |
| 100 mM | 0.0107 mL | 0.0537 mL | 0.1074 mL | 0.2684 mL |
TL12-186 Related Classifications
HY-130665 Related Classifications
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