TAI-1

TAI-1, an orally active anticancer agent, is a highly potent first-in-class Hec1 inhibitor, with a GI50 of 13.48 nM in K562 cells[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

GI50: 13.48 nM (in K562 cells)[1].

TAI-1 disrupts Hec1-Nek2 protein interaction, leads to Nek2 degradation, induces significant chromosomal misalignment in metaphase, and induces apoptotic cell death[1]. TAI-1 induces cancer cell death through the induction of cleavage of apoptotic proteins Caspase 3 and PARP and degradation of anti-apoptotic proteins MCL-1 and suggests that TAI-1 leads to activation of the apoptotic pathways[1]. TAI-1 is effective in many cancer cells, such as Chronic myeloid leukemia, Cervical cancer, Breast, metastatic-pleural, invasive ductal carcinoma, Acute myeloid leukemia, Myelogenous leukemia, Colorectal carcinoma cells, with GI50 less than 100 nM[1].

TAI-1 (20 mg/kg intravenously IV/ or 150 mg/kg per oral PO/BID) inhibits tumor growth in multiple cancer xenograft models[1]. Animal Model: C.B-17 SCID mice (6-7 weeks, 21-24 g)[1]. Dosage: 20 mg/kg intravenously IV/ or 150 mg/kg per oral PO/BID. Administration: QDx28 cycles. Result: Led to significant tumor growth retardation in Huh-7 and modest tumor inhibition was noted tor the Colo205 and MDA-MB-231 models. Did not lead to any loss in body weight.

[1]. Lynn Y L Huang, et al. Characterization of the Biological Activity of a Potent Small Molecule Hec1 Inhibitor TAI-1. J Exp Clin Cancer Res. 2014 Jan 9;33(1):6.