BLU 285
[CAS# 1703793-34-3]

Identification

• Classification: API >> Antineoplastic agents
• Name: BLU 285
• Synonyms: (alphaS)-alpha-(4-Fluorophenyl)-alpha-methyl-2-[4-[6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]-1-piperazinyl]-5-pyrimidinemethanamine
• Molecular Formula: C₂₆H₂₇FN₁₀
• Molecular Weight: 498.56
• CAS Registry Number: 1703793-34-3
• SMILES: C[C@](C1=CC=C(C=C1)F)(C2=CN=C(N=C2)N3CCN(CC3)C4=NC=NN5C4=CC(=C5)C6=CN(N=C6)C)N

Properties

• Solubility: Insoluble (1.8E^-3 g/L) (25 °C), Calc.^*
• Density: 1.42±0.1 g/cm³ (20 °C 760 Torr), Calc.^*
• Index of Refraction: 1.734, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

BLU 285 is a potent and selective small molecule inhibitor that targets specific mutations in the KIT and PDGFRA genes, which are commonly found in certain cancers. It was developed as a targeted therapy for gastrointestinal stromal tumors (GISTs) and other malignancies that exhibit resistance to first-line treatments such as imatinib. The discovery of BLU 285 was based on the understanding that mutations in the KIT and PDGFRA genes lead to the activation of abnormal signaling pathways that drive cancer cell proliferation. By inhibiting these mutant proteins, BLU 285 offers the potential for a more effective treatment for patients whose tumors are resistant to other therapies.

The development of BLU 285 was driven by the need for more effective therapies for GISTs, particularly for patients with tumors that harbor secondary mutations in the KIT or PDGFRA genes, which cause resistance to imatinib. While imatinib has revolutionized the treatment of GISTs, it is often ineffective in patients with these mutations, leading to tumor progression. BLU 285 was designed to specifically target and inhibit the mutant forms of KIT and PDGFRA, including those that are resistant to imatinib, offering a new treatment option for these difficult-to-treat cancers.

Preclinical studies and early-phase clinical trials of BLU 285 have shown promising results, with the drug demonstrating significant activity against GISTs harboring resistant mutations. In clinical trials, BLU 285 has been shown to reduce tumor size and improve progression-free survival in patients with advanced GISTs. The drug works by selectively binding to and inhibiting the mutant forms of KIT and PDGFRA, blocking the downstream signaling pathways that drive tumor growth and survival. This targeted inhibition provides a more effective and less toxic approach to treating GISTs compared to traditional chemotherapy.

In addition to its application in GISTs, BLU 285 is also being investigated for its potential use in other cancers, including systemic mastocytosis, a rare hematologic malignancy characterized by abnormal mast cell proliferation. The ability of BLU 285 to target and inhibit mutant KIT and PDGFRA receptors makes it a promising candidate for the treatment of other cancers driven by these mutations. As research continues, BLU 285 may also be explored in combination with other therapies to enhance its efficacy and broaden its application to a wider range of malignancies.

One of the key advantages of BLU 285 is its selectivity for mutant KIT and PDGFRA, which reduces the risk of off-target effects and improves its safety profile. Clinical trials have shown that BLU 285 is generally well tolerated, with side effects that are manageable and less severe compared to traditional chemotherapies. This makes it an attractive option for patients with advanced cancers who have limited treatment options due to resistance to standard therapies.

BLU 285 represents a significant advancement in the treatment of cancers with KIT and PDGFRA mutations, offering a targeted approach that is more effective and less toxic than previous therapies. Its promising results in clinical trials suggest that it could become a valuable addition to the treatment arsenal for patients with GISTs and other malignancies driven by these mutations.

References

2012. Targeting the KIT activating switch control pocket: a novel mechanism to inhibit neoplastic mast cell proliferation and mast cell activation. Leukemia, 27(2).
DOI: 10.1038/leu.2012.218

2024. Current Drug Resistance Mechanisms and Treatment Options in Gastrointestinal Stromal Tumors: Summary and Update. Current Treatment Options in Oncology, 25(10).
DOI: 10.1007/s11864-024-01272-7

2018. Targeted Therapies in the Treatment of Sarcomas. Targeted Oncology, 13(5).
DOI: 10.1007/s11523-018-0583-0