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ONC201

Catalog No.
A8724
activates p53-independent apoptosis
Grouped product items
SizePriceStock Qty
5mg
$58.00
In stock
10mg
$86.00
In stock
50mg
$250.00
In stock
100mg
$532.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

ONC201 is a first-in-class small chemical that activates p53-independent apoptosis with IC50 value less than 2.5 μM in lymphoma and leukemia cells. [1] 

ONC201 induced apoptosis in stem and progenitor AML cells and abolish the engraftment of leukemic stem cells in mice while sparing normal bone marrow cells. ONC201 induced changes in gene expression similar to those induced by the unfolded protein response (UPR) and integrated stress responses (ISRs). ONC201-treated hematopoietic cells promoted apoptosis and did not depend on increased phosphorylation of eIF2a. ONC201 also forbid mammalian target of rapamycin complex 1 (mTORC1) signaling, likely through ATF4-mediated induction of the mTORC1 inhibitor DDIT4. Overexpression of BCL-2 protected against ONC201-induced apoptosis, and the combination of ONC201 and the BCL-2 antagonist ABT-199 synergistically increased apoptosis. [1] 

In solid tumors, ONC201 caused late-stage induction of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) death receptor 5 (DR5) and promoted the transcription of TRAIL gene. ONC201 has substantial antitumor activity in preclinical models in various advanced solid tumors with infrequent oral dosing and without toxicity in normal cells in culture and in vivo [2]. Preclinical studies demonstrated broad synergism of ONC201 with established anticancer therapies, including the depletion of colorectal cancer stem cells [3]. 

ONC201 induced p53-independent apoptosis and cell cycle arrest in acute myeloid leukemia (AML) and mantle cell lymphoma (MCL) samples from patients; these embraced samples from patients with genetic abnormalities associated with poor prognosis or cells that had produced resistance to the nongenotoxic drugs ibrutinib and bortezomib. [1] 

References: 

1.ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies.Sci Signal. 2016 Feb 16;9(415):ra17. 

2.Dual in activation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects. Sci. Transl. Med. 5, 171ra117 (2013). 

3.Genetic and pharmacological screens converge in identifying FLIP, BCL2 and IAP proteins as key regulators of sensitivity to the TRAIL-inducing anti-cancer agent ONC201/TIC10. Cancer Res. 75, 1668–1674 (2015).

Chemical Properties

Physical AppearanceA crystalline solid
StorageStore at -20°C
M.Wt386.49
Cas No.1616632-77-9
FormulaC24H26N4O
Solubilityinsoluble in H2O; ≥10 mg/mL in EtOH with ultrasonic; ≥16 mg/mL in DMSO
Chemical Name7-benzyl-4-(2-methylbenzyl)-1,2,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(4H)-one
SDFDownload SDF
Canonical SMILESCC1=CC=CC=C1CN(C2=NCCN32)C(C(C4)=C3CCN4CC5=CC=CC=C5)=O
Shipping ConditionShip with blue ice, or upon other requests.
General tipsFor obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. We do not recommend long-term storage for the solution, please use it up soon.

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