How Do FLT3 Inhibitors Work?

Reviewed on 8/10/2023

How do FLT3 inhibitors work?

FLT3 inhibitors are medications used in the treatment of acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, and other malignancies including thyroid, kidney, liver and gastrointestinal cancers, and systemic mastocytosis. FLT3 inhibitors are small molecule drugs that penetrate into the cell and target a specific cellular mechanism to control cancer cell proliferation.

FMS-like tyrosine kinase 3 (FLT3) is a protein molecule known as receptor tyrosine kinase, encoded by the FLT3 gene, found primarily in the membrane of early blood-cell forming (hematopoietic) progenitor cells. Activation of FLT3 receptor initiates a signaling cascade that promotes survival, proliferation and differentiation of immature cells into specific mature blood cells.

Mutations in FLT3 gene lead to uncontrolled growth and proliferation of abnormal blood cells, which originate most often in white cells, but other blood cells too, causing blood cancers. FLT3 inhibitors bind to FLT3 receptors and prevent their activation and the signaling cascade that leads to proliferation of cancerous blood cells.

FLT3 gene mutations are the most frequent cause of acute myeloid leukemia (AML) and are associated with poor outcome. FLT3 inhibitors are targeted therapy for AML that is FLT3 mutation-positive. Two FLT3 gene mutations are commonly found in AML, internal tandem duplication (ITD) and tyrosine kinase domain (TKD). Some FLT3 inhibitors inhibit both, while some inhibit only FLT3-ITD mutation.

First generation FLT3 inhibitors include midostaurin, sunitinib, sorafenib, ponatinib, lestaurtinib and tandutinib, of which only midostaurin is FDA-approved for AML. Second generation FLT3 inhibitors include gilterintinib and quizartinib, approved for AML, and crenolanib in clinical trials. Sorafenib and quizartinib inhibit only FLT3-ITD mutation, while midostaurin, giltertinib and quizartinib inhibit ITD and TKD mutations.

The first generation FLT3 inhibitors also inhibit many other tyrosine kinase proteins and hence they are more potent and used to treat many cancers other than blood cancers as well, but they also have more adverse effects. The second generation FLT3 inhibitors are highly specific to FLT3 and affect very few other kinases.

How are FLT3 inhibitors used?

FLT3 inhibitors are available as oral capsules or tablets and are approved by the FDA for use in the treatment of adults with:

First Generation:


  • Acute myeloid leukemia
  • Systemic mastocytosis


  • Gastrointestinal stromal tumor

Renal cell carcinoma

Pancreatic neuroendocrine tumors


  • Renal cell carcinoma
  • Hepatocellular carcinoma
  • Thyroid cancer


Chronic myeloid leukemia

Acute lymphoblastic leukemia

Second Generation:


  • Acute myeloid leukemia


  • Acute myeloid leukemia

What are the side effects of FLT3 inhibitors?

Some side effects of FLT3 inhibitors used to treat acute myeloid leukemia include the following:

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

What are names of some FLT3 inhibitors?

Generic and brand names of FLT3 inhibitors include:

First generation:

  • Iclusig
  • lestaurtinib (Investigational)
  • midostaurin
  • Nexavar
  • ponatinib
  • Rydapt
  • sorafenib
  • sunitinib
  • Sutent
  • tandutinib (Investigational)

Second generation:

  • crenolanib (Investigational)
  • gilteritinib
  • quizartinib
  • Xospata
  • Vanflyta

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