APG-2449 Chemical Properties

Boiling point:

787.4±70.0 °C(Predicted)

Density 

1.271±0.06 g/cm3(Predicted)

pka

7.96±0.40(Predicted)

form 

Solid

color 

Off-white to light yellow

APG-2449 Usage And Synthesis

Description

APG-2449 is an orally available kinase inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), focal adhesion kinase (FAK) and the receptor tyrosine kinase C-ros oncogene 1 (ROS1), with potential antineoplastic activity. Upon administration, ALK/FAK/ROS1 inhibitor APG-2449 selectively binds to and inhibits ALK, FAK and ROS1 kinases. The inhibition leads to disruption of ALK-, FAK- and ROS1-mediated signal transduction pathways and eventually inhibits tumor cell growth in ALK-, FAK- and ROS1-overexpressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development; its dysregulation and gene rearrangements are associated with a variety of tumors. The cytoplasmic tyrosine kinase FAK, a signal transducer for integrins, is upregulated and constitutively activated in various tumor types; it plays a key role in tumor cell migration, proliferation, survival, and tumor angiogenesis. ROS1, overexpressed in certain cancer cells, plays a key role in cell growth and survival of cancer cells.

Uses

APG-2449 is an orally active inhibitor of ALK/ROS1/FAK. APG-2449 exerts potent and durable antitumor activity in human non-small-cell lung cancer (NSCLC) and ovarian tumor models.

References

[1] DOUGLAS D FANG. Discovery of a novel ALK/ROS1/FAK inhibitor, APG-2449, in preclinical non-small cell lung cancer and ovarian cancer models.[J]. ACS Applied Electronic Materials, 2022: 752. DOI:10.1186/s12885-022-09799-4.
[2] YUXIANG MA. FAK inhibition with novel FAK/ALK inhibitor APG-2449 could overcome resistance in NSCLC patients who are resistant to second-generation ALK inhibitors.[J]. Journal of Clinical Oncology, 2023. DOI:10.1200/jco.2023.41.16_suppl.9015.
[3] HONGYUN ZHAO. First-in-human phase I results of APG-2449, a novel FAK and third-generation ALK/ ROS1 tyrosine kinase inhibitor (TKI), in patients (pts) with second-generation TKI-resistant ALK/ROS1+ non–small cell lung cancer (NSCLC) or mesothelioma.[J]. Journal of Clinical Oncology, 2022. DOI:10.1200/jco.2022.40.16_suppl.9071.

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