DefinitionThis section has been translated automatically.
Tirbanibulin is a topical microtubule inhibitor with a selective antiproliferative mechanism of action.
Pharmacodynamics (Effect)This section has been translated automatically.
Tirbanibulin is a "non-ATP-competitive inhibitor of the proto-oncogenic non-receptor tyrosine kinase(SRC)" and at the same time a strong tubulin inhibitor (see microtubules below).
Tirbanibulin inhibits the SRC signaling pathway. The tyrosine kinase SRC, formerly known as C-SRC (SRC = acronym for "cellular and sarcoma") is a tyrosine protein kinase that is associated with the cell membrane. SRC is a protooncogene and is considered the best-studied protooncogene of all.
In cell-based experiments, tirbanibulin has been shown to induce tubulin depolymerization and cell cycle arrest in the G2/M phase at low nanomolar concentrations. It acts similarly to colchicine (Niu L et al. 2019). It reversibly binds to the colchicine binding site on β-tubulin and thus triggers a cellular effect (G2/M cell cycle arrest). The reversible binding of tirbanibulin explains its clinically low toxicity (Niu L et al. 2019).
You might also be interested in
Field of application/useThis section has been translated automatically.
Tirbanibulin, applied in ointment form, is indicated for the field therapy of non-hyperkeratotic, non-hypertrophic actinic keratoses (Olsen grade I) on the face or scalp in adults. Tirbanibulin is supplied in ointment form and is intended for external use only. The preparation is well tolerated and highly effective.
Dosage and method of useThis section has been translated automatically.
Tirbanibulin ointment should be applied in a thin layer to the treatment area of up to 25 cm2 over a treatment cycle of five consecutive days once a day on the treatment area on the face or scalp. The therapeutic effect can be assessed around eight weeks after the start of treatment.
The treatment area should be cleaned with water and a mild soap before application and then dried. The ointment should then be squeezed out of the disposable sachet onto a fingertip and applied evenly in a thin layer to the entire treatment area up to a maximum of 25 cm2. It is recommended to apply the ointment at approximately the same time every day. The treated area should not be washed or touched for a period of approx. 8 hours.
Caution: Wash hands with soap and water before and immediately after applying the ointment!
Undesirable effectsThis section has been translated automatically.
- The most commonly reported adverse reactions were local skin reactions. At the application site, these included: Erythema (91%)
- scaling (82%)
- crusting (46%)
- swelling (39%)
- Erosion/ulceration (12%)
- Pain (10%)
- Itching (9%)
- Vesicle/pustule formation (8%)
PreparationsThis section has been translated automatically.
Klisyri ® 10 mg /g ointment
Note(s)This section has been translated automatically.
Tirbanibulin was approved for medical use in the USA in December 2020. It is the first representative of a new class of active ingredients (first in class) in this area of application. Approval for the European Union followed in July 2020.
LiteratureThis section has been translated automatically.
- S3 guideline Actinic keratosis and squamous cell carcinoma of the skin. AWMF guideline 032/022OL; March 2020.
- Blauvelt A et al. (2021) Phase 3 trials of tirbanibulin ointment for actinic keratosis. N Engl J Med 384: 512-20.
- Klisyri (Almirall) package insert: https://image.wub service.de/resources/static/des/210901/12/85/128549.pdf
Niu L et al. (2019) Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of β-tubulin explains KXO1's low clinical toxicity. J Biol Chem 294:18099-18108.
