TYD-68
Based on 1 Customer Validation
TYD-68 is a CRBN-recruiting TYK2 PROTAC degrader with a DC50 of 0.42 nM, and displays selectivity against JAK1/JAK2-dependent signaling pathways. TYD-68 inhibits TYK2-mediated signaling, exerts therapeutic efficacy in murine psoriasis models, reduces PASI scores, downregulates TYK2 protein levels and decreases the secretion of proinflammatory cytokines, TYD-68 can be used for the study of psoriasis and other TYK2-driven autoimmune diseases.
(Pink: Tyk2 ligand (HY-173359); Blue: Cereblon ligand (HY-14658); Black: linker (HY-W007732B)).
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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 : 99.54%
- CAS 番号: 3110703-72-2
- 分子式: C43H40FN11O7
- 分子量:841.85
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保管条件:
-20°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from 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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生物活性
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化学情報
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溶剤 & 溶解度
- プロトコル
- 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
[1]|
Tyk2 0.42 nM (DC50) |
体外実験
TYD-68 (compound 15t) (0.01-300 nM; 10 h) degrades TYK2 in Jurkat cells with a DC50 of 0.42 nM and a Dmax of 95%[1].
TYD-68 (1-100 nM; 10 h) selectively degrades TYK2 without affecting JAK1, JAK2, or JAK3 protein levels in Jurkat cells[1].
TYD-68 (30 nM; 4 h) shows proteome-wide degradation selectivity for TYK2 over 6873 detected proteins, with no downregulation of Ikaros or Aiolos[1].
TYD-68 (10 nM; 2-36 h) induces rapid and sustained TYK2 degradation, with significant degradation observed at 4 h and maximal degradation (~90%) at 10 h persisting up to 36 h[1].
TYD-68 (10 nM; 24 h treatment + 24 h washout) shows reversible and long-lasting TYK2 degradation[1].
TYD-68 (5 nM; 10 h) degradation of TYK2 is blocked by pre-treatment with Thalidomide (HY-14658) or Deucravacitinib (HY-117287)[1].
TYD-68 (5 nM; 10 h) degradation of TYK2 is abolished by pre-treatment with MG-132 (HY-13259), Bortezomib (HY-10227), or Pevonedistat (MLN4924) (HY-70062)[1].
TYD-68 (10 nM; 10 h) combined with Cycloheximide (CHX) (HY-12320) significantly reduces TYK2 protein stability, decreasing the half-life of TYK2[1].
TYD-68 (0.1-1000 nM; 1 h pre-incubation + 1 h stimulation) inhibits IL-12-induced STAT4 phosphorylation in CD4+ T cells of human PBMCs with an IC50 of 8.6 nM, and inhibits IFN-α-induced STAT1 phosphorylation in Jurkat cells with an IC50 of 6.7 nM[1].
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 (human T-cell leukemia), HaCaT cells (human keratinocytes)
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Concentration:1, 10, 100 nM
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Incubation Time:10 h
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Result:Degraded TYK2 with DC50 of 0.42 nM and Dmax of 95% in Jurkat cells.
Showed dose-dependent TYK2 degradation in HaCaT cells.
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Cell Line:Jurkat cells
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Concentration:1, 10, 100 nM
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Incubation Time:10 h
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Result:Degraded TYK2 without affecting JAK1, JAK2, or JAK3 protein levels.
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Cell Line:Jurkat cells
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Concentration:10 nM
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Incubation Time:0, 2, 4, 6, 8, 10, 12, 24, 36 h
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Result:Observed significant degradation at 4 h.
Showed maximal degradation (approximately 90%) at 10 h persisting up to 36 h.
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Cell Line:Jurkat cells
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Concentration:10 nM
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Incubation Time:0, 4, 8, 12, 24 h washout
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Result:Exhibited reversible TYK2 degradation after 24 h washout.
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Cell Line:Jurkat cells
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Concentration:5 nM
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Incubation Time:10 h
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Result:Induced TYK2 degradation, and this degradation could be blocked by Thalidomide and Deucravacitinib.
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Cell Line:Jurkat cells
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Concentration:5 nM
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Incubation Time:2 h
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Result:Induced TYK2 degradation, and this degradation could be abolished by MG-132, Bortezomib, and MLN4924.
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Cell Line:Jurkat cells
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Concentration:10 nM
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Incubation Time:1, 2, 4, 6, 8 h
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Result:Combined with CHX significantly reduced TYK2 half-life.
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Cell Line:Jurkat cells
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Concentration:0.1, 0.3, 1, 3, 10, 30, 100 nM
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Incubation Time:10 h
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Result:Inhibited IFN-α-induced STAT1 phosphorylation with IC50 of 6.7 nM.
Parmacokinetics
| Species | Dose | Route | Cmax | Tmax | AUC0-t |
|---|---|---|---|---|---|
| Mice[1] | 5 mg/kg | i.p. | 1305 ng/mL | 0.4 h | 4766 ng/mL·h |
体内実験
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:IMQ-induced psoriasis model in female BALB/c mice[1]
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Dosage:5 mg/kg
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Administration:i.p.; once daily for 7 days
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Result:Ameliorated IMQ-induced psoriasis in mice.
Reduced PASI scores, TYK2 protein expression in skin, Th17 cell infiltration, and proinflammatory cytokines (IL-17, IL-23, IFN-α) in serum and skin tissues, without affecting body weight.
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Animal Model:Pharmacokinetics study in male ICR mice[1]
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Dosage:5 mg/kg
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Administration:i.p.; single dose
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Result:Showed favorable pharmacokinetic properties in mice, with Cmax of 1305 ng/mL, Tmax of 0.4 h, and AUC0-t of 4766 h·ng/mL.
化学情報
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CAS 番号 3110703-72-2
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性状 Solid
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分子量 841.85
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分子式 C43H40FN11O7
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Color Light yellow to yellow
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SMILES
COC1=C(C=CC=C1C2=NC=C(C=N2)F)NC3=CC(NC4=CC=C(C=N4)C(NC5CCC(CC5)NC6=CC7=C(C=C6)C(N(C7=O)C8C(NC(CC8)=O)=O)=O)=O)=NC=C3C(NC)=O
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
-20°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
溶剤 & 溶解度
体外:
DMSO : 100 mg/mL (118.79 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 (protect from light). 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 (protect from light). 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 (2.97 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. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from 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.
プロトコル
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Imiquimod-Induced Psoriasiform Dermatitis
Imiquimod (IMQ)-induced psoriasiform dermatitis is a widely used murine model in which topical application of IMQ, a Toll-like receptor 7 (TLR7) agonist, triggers innate immune activation in the skin and induces a psoriasis-like inflammatory cascade characterized by epidermal hyperplasia, immune cell infiltration, and cytokine production dominated by the IL-23/IL-17 axis. This inflammatory response is mediated through activation of dendritic cells and downstream induction of IL-23, IL-17A, IL-22, and related pro-inflammatory mediators, recapitulating key features of human plaque psoriasis and enabling mechanistic and therapeutic studies. The model is commonly induced using Aldara (5% IMQ cream) applied topically to murine skin, resulting in rapid onset of erythema, scaling, and thickening that can be quantified as disease severity indices and validated histologically.
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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取扱説明書 (2659 KB)
参考文献
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 (protect from light). 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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.1879 mL | 5.9393 mL | 11.8786 mL | 29.6965 mL |
| 5 mM | 0.2376 mL | 1.1879 mL | 2.3757 mL | 5.9393 mL | |
| 10 mM | 0.1188 mL | 0.5939 mL | 1.1879 mL | 2.9697 mL | |
| 15 mM | 0.0792 mL | 0.3960 mL | 0.7919 mL | 1.9798 mL | |
| 20 mM | 0.0594 mL | 0.2970 mL | 0.5939 mL | 1.4848 mL | |
| 25 mM | 0.0475 mL | 0.2376 mL | 0.4751 mL | 1.1879 mL | |
| 30 mM | 0.0396 mL | 0.1980 mL | 0.3960 mL | 0.9899 mL | |
| 40 mM | 0.0297 mL | 0.1485 mL | 0.2970 mL | 0.7424 mL | |
| 50 mM | 0.0238 mL | 0.1188 mL | 0.2376 mL | 0.5939 mL | |
| 60 mM | 0.0198 mL | 0.0990 mL | 0.1980 mL | 0.4949 mL | |
| 80 mM | 0.0148 mL | 0.0742 mL | 0.1485 mL | 0.3712 mL | |
| 100 mM | 0.0119 mL | 0.0594 mL | 0.1188 mL | 0.2970 mL |
TYD-68 関連分類
HY-173357 関連分類
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