Indole-based FLT3 inhibitors and related scaffolds as potential therapeutic agents for acute myeloid leukemia

Area of Science:

• Oncology
• Medicinal Chemistry
• Pharmacology

Background:

• Fms-like tyrosine kinase 3 (FLT3) mutations are common in acute myeloid leukemia (AML), leading to poor prognosis.
• Despite approved FLT3 inhibitors like Midostaurin, Gilteritinib, and Quizartinib, overall survival remains limited.
• Indole-based scaffolds have emerged as promising candidates for kinase inhibition.

Purpose of the Study:

• To review indole-based FLT3 inhibitors and related scaffolds for AML treatment.
• To analyze their chemotypes, mechanisms of action, and interactions with FLT3.
• To provide future perspectives for novel FLT3-targeted AML therapies.

Main Methods:

• Literature review of indole-based FLT3 inhibitors.
• Analysis of drug structures, mechanisms of action, and target interactions.
• Discussion of FDA-approved drugs, clinical candidates, and bioactive compounds.

Main Results:

• Indole scaffolds exhibit potent multiple kinase inhibitory activity.
• Detailed discussion of various indole-based FLT3 inhibitors, including approved drugs and clinical candidates.
• Insights into structure-activity relationships and binding modes against wild-type and mutant FLT3.

Conclusions:

• Indole-based compounds represent a valuable class of FLT3 inhibitors for AML.
• Understanding their interactions can guide the development of more effective AML therapies.
• This review highlights promising avenues for future drug discovery in FLT3-targeted AML treatment.