1616632-77-9

Basic information

• Product Name: ONC201,TIC10
• Synonyms: ONC201,TIC10;TIC-10 (ON201);2,4,6,7,8,9-Hexahydro-4-[(2-methylphenyl)methyl]-7-(phenylmethyl)imidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(1H)-one;TIC10(ONC-201);TIC 10 active isomer;7-Benzyl-4-(2-methylbenzyl)-1,2,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(4H)-on
• CAS NO: 1616632-77-9
• Molecular Formula: C₂₄H₂₆N₄O
• Molecular Weight: 386.48944
• EINECS: -0
• Product Categories: APL
• Mol File: 1616632-77-9.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 559.7±60.0 °C(Predicted)
• Appearance: /
• Density: 1.24±0.1 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility: Soluble in DMSO (up to 25 mg/ml with warming).
• PKA: 6.38±0.20(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months.
• CAS DataBase Reference: ONC201,TIC10(CAS DataBase Reference)
• NIST Chemistry Reference: ONC201,TIC10(1616632-77-9)
• EPA Substance Registry System: ONC201,TIC10(1616632-77-9)

Safety Data

• Hazardous Substances Data: 1616632-77-9(Hazardous Substances Data)

Usage

Description

TIC10 induces the expression of TNF-related apoptosis-inducing ligand (TRAIL) at 1-5 μM in a p53-independent manner. It is orally active, stable, and crosses the blood-brain barrier. The induction of TRAIL results from dual inhibition of Akt and ERK1/2 combined with nuclear translocation of the transcription factor FOXO3a. TIC10 suppresses the growth of orthotopic human glioblastoma multiforme tumors in mice.

References

1) Allen?et al.?(2013)?Dual Inactivation of Akt and ERK by TIC10 Signals Foxo3a Nuclear Translocation, TRAIL Gene Induction, and Potent Antitumor Effects, Sci. Transl. Med.?5?171ra17 2) Allen?et al.?(2015)?Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway,?Mol. Cancer.?14?99 3) Allen?et al.?(2016)?Discovery and Clinical Introduction of First-In-Class Imipridone ONC201, Oncotarget?7?74380 4) Ishizawa?et al.?(2019)?Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality, Cancer Cell?35?721

Upstream product

• 38941-29-6 N-(2-methylbenzyl)-4,5-dihydro-1H-imidazol-2-amine 
• 3939-01-3 methyl 1-benzyl-4-oxopiperidine-3-carboxylate hydrochloride 
• 89-93-0 ortho-methylbenzylamine 
• 100-39-0 benzyl bromide 
• 100-46-9 benzylamine 
• 793-19-1 bis(2-methoxycarbonylethyl)benzylamine 
• 57611-47-9 1-benzyl-4-oxo-piperidine-3-carboxylic acid methyl ester 

Relevant articles and documents

Ferrocene-containing Impiridone (ONC201) Hybrids: Synthesis, DFT modelling, in vitro evaluation, and structure–activity relationships

Inspired by the well-established clinical evidence about the interplay between apoptotic TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) mechanism and reactive oxygen species (ROS)-mediated oxidative stress, a set of novel ONC201 hybrids containing the impiridone core and one or two differently positioned ferrocenylalkyl groups were synthesised in our present work. These two types of residues have been implicated in the aforementioned mechanisms associated with cytotoxic activity. A straightforward, primary amine-based synthetic approach was used allowing the introduction of a variety of N-substituents into the two opposite regions of the heterocyclic skeleton. Reference model compounds with benzyl and halogenated benzyl groups were also synthesised and tested. The in vitro assays of the novel impiridones on five malignant cell lines disclosed characteristic structure-activity relationship (SAR) featuring significant substituent-dependent activity and cell-selectivity. A possible contribution of ROS-mechanism to the cytotoxicity of the novel metallocenes was suggested by density functional theory (DFT)studies on simplified models. Accordingly, unlike the mono-ferrocenylalkyl-substituted products, the compounds containing two ferrocenylalkyl substituents in the opposite regions of the impiridone core display a much more pronounced long-term cytotoxic effect against A-2058 cell line than do the organic impiridones including ONC201 and ONC212. Furthermore, the prepared bis-metallocene derivatives also present substantial activity against COLO-205- and EBC-1 cell lines.

Imidazo-pyrimidone Compounds, and Preparation Method and Application Thereof

Compounds of formula (I), imidazopyrimidine ketones, as well as preparations and applications thereof. Compounds and pharmaceutically acceptable salts thereof which stimulate the body to produce tumor necrosis factor-related apoptosis-inducing ligands, while avoiding the drawbacks of existing cancer treatments based on recombinant proteins and antibodies. Thus, they can provide novel options for the treatment of related tumors.

7-BENZYL-4-(2-METHYLBENZYL)-2,4,6,7,8,9-HEXAHYDROIMIDAZO [1,2-A]PYRIDO[3,4-E]PYRIMIDIN-5(1H)-ONE, ANALOGS AND SALTS THEREOF AND THEIR USE IN THERAPY

This disclosure relates to methods of treatment using compound (1) or analogs thereof, and pharmaceutically acceptable salts thereof. Also disclosed are compounds of formula (10): as defined in the specification, and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions comprising the same. Methods of treatment, such as for cancer, are provided that comprise administering the compounds and their salts to a subject in need of such treatment.