Taladegib
Based on 2 publication(s) in Google Scholar
Taladegib is a Smoothened (SMO) antagonist. Taladegib hydrochloride inhibits the Hedgehog signaling pathway, with an IC50 of 5.5 nM for suppressing GLI1 mRNA expression in DAOY cells and an IC50 of 7.6 nM in CGNP cell proliferation assays. Taladegib binds to the extracellular loop region (site 1) of the transmembrane domain of the SMO receptor, competes with cyclopamine for SMO binding, and thereby inhibits Gli-dependent transcription. Taladegib can be used in studies of Hedgehog pathway-related cancers.
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- Pureza : 99.89%
- No. CAS: 1258861-20-9
- Fòrmula: C26H24F4N6O
- Peso molecular:512.50
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) Taladegib
More
Actividad biológica
Descripciòn
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A2058 | IC50 |
>50 μM
Compound: LY2940680
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Antiproliferation activity against human A2058 cells incubated for 72 hrs by MTT assay
Antiproliferation activity against human A2058 cells incubated for 72 hrs by MTT assay
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[PMID: 32063403] |
| Daoy | IC50 |
0.79 μM
Compound: LY2940680
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Antiproliferative activity against human DaOY cells incubated for 72 hrs by MTT assay
Antiproliferative activity against human DaOY cells incubated for 72 hrs by MTT assay
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[PMID: 32063403] |
| Daoy | IC50 |
0.79 μM
Compound: LY2940680
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Antiproliferative activity against human Daoy cells assessed as inhibition of cell growth
Antiproliferative activity against human Daoy cells assessed as inhibition of cell growth
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[PMID: 33636537] |
| Medulloblastoma cell | IC50 |
43.5 nM
Compound: 3: LY-2940680
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Antiproliferative activity against Ptch+/- and p53-/- mouse medulloblastoma cells after 36 hrs by Brdu incorporation assay
Antiproliferative activity against Ptch+/- and p53-/- mouse medulloblastoma cells after 36 hrs by Brdu incorporation assay
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[PMID: 28688278] |
In Vitro
Taladegib (1-100 μM; 72 h) slightly inhibits the proliferation of primary cell cultures of mucinous IHCCA and mixed-type IHCCA, with IC50 values of 49.8 μM and 61.2 μM, respectively[2].
Taladegib potently inhibits SHH-induced GLI1 mRNA expression in human DAOY medulloblastoma cells, with a pIC50 of 8.26 and full efficacy[4].
Taladegib (20 μM; 72 h) does not induce apoptosis in primary cell cultures of mucinous IHCCA or mixed-type IHCCA[2].
Taladegib potently binds to wild-type human Smoothened, with a Ki value of 0.5 nM[3].
The binding potency of Taladegib to D473H mutant human Smoothened is significantly reduced, with a Ki value of 55 nM[3].
Taladegib potently inhibits the constitutive activity of wild-type human SMO in CHO-K1 cell membranes, with a pIC50 of 6.53, and exhibits full inverse agonist efficacy[4].
Taladegib potently inhibits the constitutive activity of the human SMOD473H mutant receptor on CHO-K1 cell membranes, with a pIC50 of 6.22, and exhibits full inverse agonist efficacy[4].
Taladegib inhibits the constitutive activity of the human SMOM2 (W535L) mutant receptor on CHO-K1 cell membranes, with a pIC50 of 5.75, and exhibits full inverse agonist potency[4].
Taladegib potently inhibits SHH-induced proliferation of rat CGNP cells, with a pIC50 of 8.12 and full efficacy[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Taladegib (1% (w/v); topical; single application) potently inhibits Hedgehog pathway activity in depilated mouse skin, reducing Gli1 mRNA by ~70-80% with low systemic plasma exposure[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:male w1118 (isoCJ1) isogenic background, elav-Gal4c155 driver line crossed with UAS-hAβ42 (Aβ-expressing/AD flies)[1]
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Dosage:100 μM (3-min memory); 100 μM (1-h memory)
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Administration:p.o.; daily; 7 days (3-min memory); p.o.; daily; 5 days (1-h memory)
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Result:Rescued Aβ-induced 3-min memory deficits, with performance index increased to levels comparable to control flies.
Rescued Aβ-induced 1-h memory deficits, with performance index increased to levels comparable to control flies.
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Animal Model:C57BL6/NCrl (female, 7 weeks old on arrival, depilation-induced Hedgehog pathway activation)[4]
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Dosage:1% (w/v)
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Administration:topical; single application
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Result:Decreased Gli1 mRNA expression by ~70-80% relative to vehicle-treated controls.
Decreased Ptch1 mRNA expression relative to vehicle-treated controls.
Achieved skin concentration of 10 ng/mg and plasma concentration of 607 ng/mL.
Ensayo clínico
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 1258861-20-9
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Appearance Solid
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Peso molecular 512.50
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Fòrmula C26H24F4N6O
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Color White to off-white
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SMILES
CN1N=CC=C1C2=C3C(C=CC=C3)=C(N=N2)N4CCC(CC4)N(C)C(C5=C(C=C(C=C5)F)C(F)(F)F)=O
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Synonyms
LY2940680
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (2)
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Journal Impact Factor
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Most Recent
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Cell Rep Med
Drug screening in 3D microtumors reveals DDR1/2-MAPK12-GLI1 as a vulnerability in cancer-associated fibroblasts. [Abstract]2025 Sep 19:102357. PMID: 40975064 -
J Genet Genomics
Reduced Smoothened level rescues Aβ-induced memory deficits and neuronal inflammation in animal models of Alzheimer's disease. [Abstract]2018 May 20;45(5):237-246. PMID: 29807798
Solvente y solubilidad
In Vitro:
DMSO : 50 mg/mL (97.56 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. 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. 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: ≥ 2.5 mg/mL (4.88 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.88 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 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.
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.
Pureza y Documentación
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Ficha de datos (281 KB)
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SDS (481 KB)
- English - EN (481 KB)
- Français - FR (481 KB)
- Deutsch - DE (481 KB)
- Norwegian - NO (481 KB)
- Español - ES (481 KB)
- Swedish - SV (481 KB)
- Italian - IT (481 KB)
- Korean - KR (481 KB)
- Portuguese - PT (481 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Ma W, et al. Reduced Smoothened level rescues Aβ-induced memory deficits and neuronal inflammation in animal models of Alzheimer's disease. Journal of genetics and genomics = Yi chuan xue bao. 2018 May 20;45(5):237-246. [Content Brief]
[2]. Fraveto A, et al. Sensitivity of Human Intrahepatic Cholangiocarcinoma Subtypes to Chemotherapeutics and Molecular Targeted Agents: A Study on Primary Cell Cultures. PloS one. 2015;10(11):e0142124. [Content Brief]
[3]. Hoch L, et al. MRT-92 inhibits Hedgehog signaling by blocking overlapping binding sites in the transmembrane domain of the Smoothened receptor. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2015 May;29(5):1817-29. [Content Brief]
[4]. Lauressergues E, et al. Pharmacological evaluation of a series of smoothened antagonists in signaling pathways and after topical application in a depilated mouse model. Pharmacology research & perspectives. 2016 Apr;4(2):e00214. [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, 2 years; -20°C, 1 year. 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 | 1.9512 mL | 9.7561 mL | 19.5122 mL | 48.7805 mL |
| 5 mM | 0.3902 mL | 1.9512 mL | 3.9024 mL | 9.7561 mL | |
| 10 mM | 0.1951 mL | 0.9756 mL | 1.9512 mL | 4.8780 mL | |
| 15 mM | 0.1301 mL | 0.6504 mL | 1.3008 mL | 3.2520 mL | |
| 20 mM | 0.0976 mL | 0.4878 mL | 0.9756 mL | 2.4390 mL | |
| 25 mM | 0.0780 mL | 0.3902 mL | 0.7805 mL | 1.9512 mL | |
| 30 mM | 0.0650 mL | 0.3252 mL | 0.6504 mL | 1.6260 mL | |
| 40 mM | 0.0488 mL | 0.2439 mL | 0.4878 mL | 1.2195 mL | |
| 50 mM | 0.0390 mL | 0.1951 mL | 0.3902 mL | 0.9756 mL | |
| 60 mM | 0.0325 mL | 0.1626 mL | 0.3252 mL | 0.8130 mL | |
| 80 mM | 0.0244 mL | 0.1220 mL | 0.2439 mL | 0.6098 mL |
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