Taladegib (LY2940680)

Catalog No.S2157

Taladegib (LY2940680) Chemical Structure

Molecular Weight(MW): 512.5

Taladegib (LY2940680) binds to the Smoothened (Smo) receptor and potently inhibits Hedgehog (Hh) signaling. Phase 1/2.

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Biological Activity

Description Taladegib (LY2940680) binds to the Smoothened (Smo) receptor and potently inhibits Hedgehog (Hh) signaling. Phase 1/2.
Targets
Smoothened [1]
In vitro

LY2940680 inhibits cancer growth in cell lines containing a mutation in the gene encoding Smoothened that researchers had previously observed in patient with cancer who developed resistance to vismodegib. [1]

In vivo LY2940680 has excellent pharmacokinetic properties in rodent and non-rodent species. LY2940680 administrated orally treats Ptch+/- p53-/- transgenic mice which spontaneously develop medulloblastoma, produces remarkable efficacy and significantly improves their survival. LY2940680 reveals rapid kinetics of anti-tumor activity through magnetic resonance imaging of these mice, and LY2940680 induces Caspase-3 activity and reduces proliferation by immunohistochemistry analysis of medulloblastoma tumors. LY2940680 inhibits Hh regulated gene expression in the subcutaneous xenograft tumor stroma and produces significant anti-tumor activity. [2]

Protocol

Solubility (25°C)

In vitro DMSO 5 mg/mL warmed (9.75 mM)
Ethanol 2 mg/mL (3.9 mM)
Water <1 mg/mL
In vivo

* 1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 512.5
Formula

C26H24F4N6O

CAS No. 1258861-20-9
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01919398 Active, not recruiting Neoplasm Metastasis Eli Lilly and Company August 2013 Phase 1
NCT01697514 Withdrawn Medulloblastoma, Childhood|Rhabdomyosarcoma Eli Lilly and Company July 2013 Phase 1
NCT01746745 Completed Healthy Volunteers Eli Lilly and Company January 2013 Phase 1
NCT01722292 Terminated Small Cell Lung Carcinoma Eli Lilly and Company January 2013 Phase 1|Phase 2
NCT01681186 Completed Healthy Volunteers Eli Lilly and Company September 2012 Phase 1

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Hedgehog/Smoothened Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID