Taladegib hydrochloride
Based on 2 publication(s) in Google Scholar
Taladegib (LY2940680) hydrochloride 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 hydrochloride 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 hydrochloride can be used in studies of Hedgehog pathway-related cancers.
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- CAS No.: 1258861-21-0
- Formule: C26H25ClF4N6O
- Masse moléculaire:548.96
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Publications Citing Use of MedChemExpress (MCE) Taladegib hydrochloride
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Activité biologique
Hydrochloride of Taladegib (LY2940680) (1-100 μM; 72 h) slightly inhibits the proliferation of primary cell cultures of mucinous-type IHCCA and mixed-type IHCCA, with IC50 values of 49.8 μM and 61.2 μM, respectively[2].
Taladegib hydrochloride potently inhibits SHH-induced GLI1 mRNA expression in human DAOY medulloblastoma cells, with a pIC50 of 8.26 and full efficacy[4].
Hydrochloride of Taladegib (20 μM; 72 h) does not induce apoptosis in primary cell cultures of mucinous IHCCA or mixed-type IHCCA[2].
Taladegib hydrochloride potently binds to wild-type human Smoothened, with a Ki value of 0.5 nM[3].
Taladegib hydrochloride exhibits significantly reduced binding affinity for the D473H mutant human Smoothened, with a Ki value of 55 nM[3].
Taladegib hydrochloride 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 (LY2940680) hydrochloride 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 hydrochloride 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 hydrochloride 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.
Hydrochloride of Taladegib (1% (w/v); topical administration; single dose) potently inhibits Hedgehog pathway activity in the skin of depilated mice, reduces Gli1 mRNA by approximately 70%-80%, and results in 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.
Chemical Information
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CAS No. 1258861-21-0
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Masse moléculaire 548.96
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Formule C26H25ClF4N6O
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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.Cl
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Synonyms
LY2940680 hydrochloride
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
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
Pureté et documentation
Références
[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]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Taladegib hydrochloride Related Classifications
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