BLU-285

• CAT Number: I004344
• CAS Number: 1703793-34-3
• Molecular Formula: C26H27FN10
• Molecular Weight: 498.57
• Purity: 98%
• Synonyms: BLU-285; BLU 285; BLU285.;(S)-1-(4-fluorophenyl)-1-(2-(4-(6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)piperazin-1-yl)pyrimidin-5-yl)ethan-1-amine
• Target: c-Kit
• Target Protein: P16234
• Solubility: Soluble in DMSO
• Appearance: Solid
• Storage: Dry, dark and at 2 - 8 °C for six months or -20°C for two years.
• IC50: IC50: 0.27 nM (KIT D816V), 0.24 nM (PDGFRA D842V)
• IUPAC Name: (1S)-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine
• InChI: InChI=1S/C26H27FN10/c1-26(28,20-3-5-22(27)6-4-20)21-13-29-25(30-14-21)36-9-7-35(8-10-36)24-23-11-18(16-37(23)33-17-31-24)19-12-32-34(2)15-19/h3-6,11-17H,7-10,28H2,1-2H3/t26-/m0/s1
• InChIKey: DWYRIWUZIJHQKQ-SANMLTNESA-N
• 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

BLU-285 (Cat No.: I004344) is a potent and selective inhibitor of KIT and PDGFRα kinases, which are involved in signaling pathways associated with cancer growth and progression. It acts by binding to the ATP-binding site of these kinases, inhibiting their activity and downstream signaling. BLU-285 has shown promising efficacy in the treatment of gastrointestinal stromal tumors (GISTs) that harbor specific mutations in KIT or PDGFRα, such as the KIT exon 17 mutations. It has demonstrated potent antitumor activity in preclinical and clinical studies, with durable responses observed in patients with advanced GISTs. BLU-285 represents a targeted therapeutic option for GISTs and holds potential for further exploration in other malignancies driven by KIT and PDGFRα mutations.

Reference

1:Cancer Discov. 2017 Feb;7(2):121-122. doi: 10.1158/2159-8290.CD-NB2016-165. Epub 2017 Jan 11. BLU-285, DCC-2618 Show Activity against GIST. PMID: 28077435 DOI: 10.1158/2159-8290.CD-NB2016-165
Abstract: Tyrosine kinase inhibitors may initially control gastrointestinal stromal tumors, but most patients eventually experience disease progression due to activation loop mutations, which are resistant to approved drugs. However, phase I trials suggest that the cancer is sensitive to two new agents: BLU-285 and DCC-2618. In addition, liquid biopsies, which were used to follow patients during the trials, may be valuable tools in tracking disease progression and assessing tumor heterogeneity.©2017 American Association for Cancer Research.

2. Cancer Discov. 2017 Nov 10. doi: 10.1158/2159-8290.CD-RW2017-211. [Epub ahead of
print]
BLU-285 Targets KIT/PDGFRA Conformation and Activating Loop Mutations.
[No authors listed]
The small-molecule inhibitor BLU-285 inhibits clinically relevant KIT and PDGFRA
mutations.
©2017 American Association for Cancer Research.
DOI: 10.1158/2159-8290.CD-RW2017-211
PMID: 29127088