1258861-20-9

Basic information

• Product Name: LY2940680
• Synonyms: Taladegib (LY2940680);4-Fluoro-N-methyl-N-[1-[4-(1-methyl-1H-pyrazol-5-yl)-1-phthalazinyl]-4-piperidinyl]-2-(trifluoromethyl)benzamide LY 2940680;LY2940680 (Taladegib);Taladegib;Taladegib hydrochloride;4-Fluoro-N-methyl-N-(1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-yl)-2-(trifluo;LY2940680;4-Fluoro-N-methyl-N-[1-[4-(1-methyl-1H-pyrazol-5-yl)-1-phthalazinyl]-4-piperidinyl]-2-(trifluoromethyl)benzamide
• CAS NO: 1258861-20-9
• Molecular Formula: C₂₆H₂₄F₄N₆O
• Molecular Weight: 512.51
• Product Categories: Inhibitors
• Mol File: 1258861-20-9.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 703.5±60.0 °C(Predicted)
• Appearance: /
• Density: 1.39
• Solubility: insoluble in H2O; ≥5.2 mg/mL in EtOH with ultrasonic; ≥51.3 mg/mL in DMSO with gentle warming and ultrasonic
• PKA: 7.94±0.30(Predicted)
• CAS DataBase Reference: LY2940680(CAS DataBase Reference)
• NIST Chemistry Reference: LY2940680(1258861-20-9)
• EPA Substance Registry System: LY2940680(1258861-20-9)

Safety Data

• Hazardous Substances Data: 1258861-20-9(Hazardous Substances Data)

Usage

Description

LY2940680 is an antitumor agent that specifically targets and binds to the human Smoothened (Smo) receptor, a GPCR-like receptor involved in the Hedgehog (Hh) signaling pathway. This pathway plays a crucial role in regulating gene expression through the Gli transcription factors. By inhibiting Sonic Hh-induced Gli1 expression, LY2940680 demonstrates potential anticancer activity and is currently under clinical investigation.

Uses

Used in Anticancer Applications:
LY2940680 is used as an antitumor agent for inhibiting the Hedgehog (Hh) signaling pathway, which is often dysregulated in various cancers. By targeting the Smoothened (Smo) receptor, LY2940680 can potentially suppress tumor growth and progression, making it a promising candidate for cancer treatment.
Used in Clinical Research:
LY2940680 is used as a research tool for studying the role of the Hedgehog (Hh) signaling pathway in cancer and other diseases. Its ability to inhibit the Smo receptor and Sonic Hh-induced Gli1 expression makes it a valuable compound for understanding the molecular mechanisms underlying Hh signaling and its implications in disease development.
Used in Drug Development:
LY2940680 serves as a starting point for the development of new drugs targeting the Hedgehog (Hh) signaling pathway. Its potent inhibition of the Smo receptor and potential anticancer activity provide a foundation for designing and optimizing novel therapeutics to treat cancers driven by aberrant Hh signaling.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, LY2940680 is used as a lead compound for the development of new cancer therapies. Its unique mechanism of action and potential to inhibit the Hedgehog (Hh) signaling pathway make it an attractive candidate for further research and development, with the goal of bringing new, effective treatments to patients in need.

Biological Activity

ly2940680 is a selective inhibitor of smo receptor and thus inhibits hh signaling pathway [1].smoothened(smo) receptor is a member of class f g protein-coupled receptors, which plays an important role in the main transducer of the hedgehog (hh) signaling pathway that implicated in a wide range of developmental and adult processes [2].ly2940680 is a potent smo receptor inhibitor that binds mostly to extracelluar loops and has a different functioning site with the reported smo receptor inhibitor sant-1 which binds to 7tm [2]. when tested with cell lines containing a mutation in the gene encoding smoothened that researchers had previously observed in patient with cancer who developed resistance to vismodegib, ly2940680 inhibited cell proliferation [3].many studies have shown that hh signaling pathway plays a pivotal role in cscs and hh inhibition caused many aspects of transformation attributed to cscs. in patients with basal cell carcinoma and medulloblastoma, ly2940680 showed good efficacy as a monotherapy [1].

references

[1]. justilien, v. and a.p. fields, molecular pathways: novel approaches for improved therapeutic targeting of hedgehog signaling in cancer stem cells. clin cancer res, 2015. 21(3): p. 505-13.[2]. hoch, l., et al., mrt-92 inhibits hedgehog signaling by blocking overlapping binding sites in the transmembrane domain of the smoothened receptor. faseb j, 2015. 29(5): p. 1817-29.[3]. redmond, e.m., et al., investigational notch and hedgehog inhibitors--therapies for cardiovascular disease. expert opin investig drugs, 2011. 20(12): p. 1649-64.

Upstream product

• 1258861-50-5 N-methyl-1-[4-(2-methylpyrazol-3-yl)phthalazin-1-yl]piperidin-4-amine 
• 189807-21-4 2-trifluoromethyl-4-fluorobenzoyl chloride 
• 847818-74-0 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole 
• 3612-20-2 1-phenylmethyl-4-piperidone 
• 7006-50-0 1-benzyl-N-methylpiperidin-4-amine 

Relevant articles and documents

A novel and efficient route for synthesis of Taladegib

Taladegib (LY-2940680), a small molecule Hedgehog signalling pathway inhibitor, was obtained from N-benzyl-4-piperidone via Borch reductive amination, acylation with 4-fluoro-2-(trifluoromethyl)benzoyl chloride, debenzylation, substitution with 1,4-dichlorophthalazine and Suzuki cross-coupling reaction with 1-methyl-1H-pyrazole-5-boronic acid. The advantages of this synthesis route were the elimination of Boc protection and deprotection and the inexpensive starting materials. Furthermore, the debenzylation reaction was achieved with simplified operational procedure using ammonium formate as hydrogen source that provided high reaction yield. This synthetic procedure was suitable for large-scale production of the compound for biological evaluation and further study.

DISUBSTITUTED PHTHALAZINE HEDGEHOG PATHWAY ANTAGONISTS

The present invention provides novel 1,4-disubstituted phthalazine hedgehog pathway antagonists useful in the treatment of cancer.