Tyrosine Kinase Inhibitor

Imatinib

An oral BCR-ABL tyrosine kinase inhibitor used for Philadelphia chromosome-positive leukemias and KIT-positive GIST.

Also called imatinib mesylate (US name of the salt in medicines).

Drug card

Class: Tyrosine kinase inhibitor
How it works: Blocking an overactive tyrosine kinase that drives cancer cells to divide
Used for: Philadelphia-positive chronic myeloid leukemia
KIT-positive gastrointestinal stromal tumor (GIST)
Philadelphia-positive acute lymphoblastic leukemia
Known for: Fluid retention, with swelling around the eyes
Muscle cramps and bone or muscle pain
Its name: -tinib means a tyrosine kinase inhibitor

Study it as a flashcard, and it comes back before you forget it.

Mechanism of action

How does imatinib work?

Imatinib blocks BCR-ABL, the always-active tyrosine kinase made by the Philadelphia chromosome in chronic myeloid leukemia, so the leukemic cells stop multiplying and undergo apoptosis. It also blocks the KIT (CD117) and PDGF receptor kinases, which is why it works in KIT-positive gastrointestinal stromal tumors.

Uses

What is imatinib used for?

Philadelphia-positive chronic myeloid leukemia
KIT-positive gastrointestinal stromal tumor (GIST)
Philadelphia-positive acute lymphoblastic leukemia

Side effects

Side effects of imatinib

Fluid retention, with swelling around the eyesKnown for
Muscle cramps and bone or muscle painKnown for
Nausea and vomiting
Low blood counts (neutropenia, low platelets, anemia)Serious
Liver damageSerious
Heart failureSerious
Heart damage when eosinophil counts are highSerious
Serious bleeding (hemorrhage)Serious
Bleeding or perforation in the gutSerious
Blistering skin reactions (Stevens-Johnson syndrome)Serious
Decline in kidney functionSerious
Harm to the fetusSerious

Known for marks what an exam expects you to know it for.

Watch for

Cautions and what sets it apart

Strong CYP3A4 inhibitors and grapefruit raise its levels, inducers lower them, and it raises levels of other CYP3A4 drugs.
Heparins are preferred to warfarin when a patient on imatinib needs an anticoagulant.
Patients are weighed often to catch fluid retention; blood counts and liver tests are checked during treatment.
Pregnancy: it can harm the fetus, so effective contraception is needed.

Good to know: Nilotinib and dasatinib, later BCR-ABL inhibitors, can work in leukemias that have become resistant to imatinib.

Remember it

A way to remember it

Small pill, works inside the cell

Tyrosine kinase inhibitors are small molecules swallowed as tablets that slip into the cell and block the kinase there; monoclonal antibodies are large proteins, usually given by drip, that bind targets on the cell surface.

Written for biofideX

Its name

-tinib means tyrosine kinase inhibitor
Imatinib blocks the BCR-ABL kinase in chronic myeloid leukemia. Sub-stems name the target: -citinib for JAK (tofacitinib), -brutinib for BTK (ibrutinib), -ertinib for EGFR (osimertinib).
Every drug name stem

Its class

Tyrosine kinase inhibitors

Tyrosine kinases relay growth signals by putting phosphate groups on tyrosine in their target proteins, and in some cancers one of them is stuck in the on position (BCR-ABL in chronic myeloid leukemia, EGFR in some lung cancers). These small molecules get inside the cell and bind that kinase, most of them by competing with ATP for its catalytic site. The signal stops, so cells that depend on it stop dividing or die.

Easily mixed up with HER2-targeted antibodies and PD-1 checkpoint inhibitors.

Sources

Checked against

Written for biofideX in plain words, after checking these references:

For learning pharmacology, not for treatment decisions: no doses are given, and a prescriber, pharmacist or the product's own label is the word on any one patient. Spotted a mistake? Tell us and we'll correct it.

Practice it

Targeted therapy and the immune system

Imatinib is one of 13 drugs practiced together here: their classes, how they work, what they treat and what they're known for.

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