An orally bioavailable, non-peptidomimetic antagonist of both X chromosome-linked inhibitor of apoptosis protein (XIAP) and cellular IAP 1 (cIAP1), with potential antineoplastic and pro-apoptotic activities. Upon administration, XIAP/cIAP1 antagonist ASTX660 selectively binds to and inhibits the activity of XIAP and cIAP1. This restores and promotes the induction of apoptotic signaling pathways in cancer cells, and inactivates the nuclear factor-kappa B (NF-kB)-mediated survival pathway. XIAP and cIAP1 are overexpressed by many cancer cell types and suppress apoptosis by inhibiting the activity of certain caspases; they promote both cancer cell survival and chemotherapy resistance.
Tolinapant 细胞实验
Cell Line
Concentration
Treated Time
Description
References
A549 (Human)
0.014-10 µM
48-80 hours
To evaluate the immune-mediated killing effects of Tolinapant on A549 cells. Results showed that Tolinapant significantly increased apoptosis of A549 cells in the presence of activated PBMCs.
Blood Adv. 2021 Oct 26;5(20):4003-4016.
HH (Human)
0.001-10 µM
72 hours
To evaluate the cytotoxic effects of Tolinapant on the human TCL cell line HH. Results showed that Tolinapant had minimal impact on HH cell viability within 72 hours, but the effect was enhanced in the presence of TNF-α.
Blood Adv. 2021 Oct 26;5(20):4003-4016.
BW5147.G.1.4 (Mouse)
0.001-10 µM
72 hours
To evaluate the cytotoxic effects of Tolinapant on the mouse TCL cell line BW5147.G.1.4. Results showed that Tolinapant significantly reduced cell viability within 72 hours, especially in the presence of TNF-α.
Blood Adv. 2021 Oct 26;5(20):4003-4016.
MDA-MB-231 cells
4.4 nM (GI50)
Evaluate the inhibitory effect of Tolinapant on MDA-MB-231 cells
Pharmacol Res Perspect. 2024 Dec;12(6):e70030.
Tolinapant 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
BW5147 syngeneic model
Oral
25 mg/kg
Once daily for 15 days
To evaluate the antitumor effects of Tolinapant in the BW5147 syngeneic model. Results showed that Tolinapant treatment led to complete tumor regression, and no tumor recurrence was observed within 30 days after treatment cessation.
Blood Adv. 2021 Oct 26;5(20):4003-4016.
Mice
MDA-MB-231 xenograft models
Oral
30 mg/kg
Once daily
Evaluate the efficacy of Tolinapant in MDA-MB-231 xenograft models
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