| Identification | Back Directory | [Name]
2,4-Pyrimidinediamine, 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-[1,2,3,6-tetrahydro-1-(tetrahydro-2H-pyran-4-yl)-4-pyridinyl]phenyl]- | [CAS]
2196186-84-0 | [Synonyms]
APG-2449
2,4-Pyrimidinediamine, 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-[1,2,3,6-tetrahydro-1-(tetrahydro-2H-pyran-4-yl)-4-pyridinyl]phenyl]- | [Molecular Formula]
C33H42ClN5O4S | [MOL File]
2196186-84-0.mol | [Molecular Weight]
640.24 |
| Chemical Properties | Back Directory | [Boiling point ]
787.4±70.0 °C(Predicted) | [density ]
1.271±0.06 g/cm3(Predicted) | [form ]
Solid | [pka]
7.96±0.40(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [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. |
|
|