Antimetastatic and Tumor Growth Inhibition Activity of Polysaccharide from Helianthus Tuberosus L.

e16741 Background: Owing to its high mortality and lack of effective treatments, there is therefore an urgent unmet need to develop novel and more effective treatments for pancreatic cancer (PC). ABP-1119 is a novel and potent multi-TRK Inhibitor for several PC-related prime tyrosine kinases (TRKs), such as EGFR, HER2, ALK, and BTK. Pre-clinical studies with ABP-1119, especially study to evaluate its tumor growth inhibition activity on pancreatic tumor xenograft model, are planned. Methods: (1) Mobility-Shift Assay used to Analyze the multi-TRK (such as EGFR, HER2, ALK, and BTK) Inhibition activity of new anti-tumor compounds, (2) CTG Assay used to analyze the inhibition activity of Mia-Paca-2 Cell Line, (3) Anti-tumor inhibition study of ABP-1119 with the pancreatic cancer nude mice, (4) Safety studies of ABP-1119 for Ames, hERG, and maximum tolerated dose (MTD). Results: It was determined that its multi-TRK inhibition activity (IC50) of ABP-1119 was 0.9nM to EGFR, 4.8nM to HER2, 0.9nM to ALK, and 2.1nM to BTK, respectively. Its inhibition activity for Cell Line Mia-Paca-2 was 0.06 µM. In anti-tumor inhibition study with the Mia-Paca-2 tumor nude mice for 14 days, the anti-tumor inhibition rate of ABP-1119 (50 mg/kg, QD) was over 82% (vs Erlotinib as a positive control, 50mg/kg, QD, inhibition rate: 48%), and no any death and other serious side effects were observed during the nude mice tests. Moreover, for other safety issues, its Ames is negative and hERG is > 30 µM, and no test-article related death or adverse events occurred in MTD studies with ABP-1119 (100mg/kg, QD) for 14 days. ABP-1119 also had very good metabolic stability in Human (T1/2 = 2.5hr). Conclusions: Based on our completed preclinical study results, ABP-1119 is a novel and potent multi-TRK Inhibitor, showing excellent enzymatic activity, prominent in-vitro anti-cancer activity, and good tumor growth inhibition activity with tolerable toxicity in pancreatic tumor xenograft in nude mice model. It is warranted to continue further investigation in pancreatic cancer.

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Evaluation of tumor growth inhibition activity of a novel multi-TRK inhibitor ABP-1130 on glioblastoma xenograft model.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e14507 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e14507-e14507

Author(s):

Zheng-Yun James Zhan ◽

Wanlong Pan ◽

Hao Zhang

Keyword(s):

Tumor Growth ◽

Growth Inhibition ◽

Nude Mice ◽

Tyrosine Kinases ◽

Xenograft Model ◽

Tumor Growth Inhibition ◽

Inhibition Activity ◽

Inhibition Study ◽

Tumor Inhibition ◽

The Brain

e14507 Background: Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive cancer that begins within the brain. Glioblastoma is a difficult to treat tumor with therapeutics limited by their ability to cross the blood brain barrier. Receptor tyrosine kinases (TRK) inhibitor is reported one of therapies for glioblastoma. ABP-1130 is a novel and potent small molecular multi-TRK Inhibitor for several prime tyrosine kinases (TRKs), such as EGFR, HER2, C-Met, and BTK with potential to treat glioblastoma. Pre-clinical studies with ABP-1130, especially study to evaluate its tumor growth inhibition effect on glioblastoma xenograft model, are planned in progress. Methods: (1) Mobility-Shift Assay used to Analyze the multi-TRK (such as EGFR, HER2, C-Met, and BTK) Inhibition activity of new anti-tumor compounds, (2) CTG Assay used to analyze the inhibition activity of LN-229 Cell Line, (3) Anti-tumor inhibition study of ABP-1130 with the brain cancer nude mice, (4) Safety studies of ABP-1130 for Ames, hERG, and MTD. Results: It was determined that its multi-TRK inhibition activity (IC50) of ABP-1130 was 7nM to EGFR, 3.6nM to HER2, 3.2nM to C-Met, and 3.7nM to BTK, respectively. Its inhibition activity for Cell Line LN-229 was 0.02 µM. In anti-tumor inhibition study with the LN-229 tumor nude mice for 28 days, the anti-tumor inhibition activity of ABP-1130 (40 mg/kg, QD) was significantly observed, and the average volume of brain tumors in nude mice (six mice/each group) was reduced from 122 mm3 to < 10mm3 (vs Pazopanib as a positive control, 50mg/kg, tumor volume increased from 123 to 867mm3). Moreover, for other safety issues, its Ames is negative and hERG is > 30 µM, and no test-article related death or adverse events occurred in maximum tolerated dose (MTD) studies with ABP-1130 (100mg/kg, QD) for 14 days. ABP-1130 also had very good metabolic stability in Human (T1/2 = 193min). Conclusions: Based on our completed preclinical study results, ABP-1130 is a novel and potent multi-TRK Inhibitor, showing excellent enzymatic activity, prominent in-vitro anti-cancer activity, and significant tumor growth inhibition activity with tolerable toxicity in glioblastoma tumor xenograft in nude mice model. It is highly warranted to continue further investigation in glioblastoma.

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