Tirbanibuline

Tirbanibulin is a topical microtubule inhibitor with a selective antiproliferative mechanism of action.

Tirbanibulin is not only a "non-ATP-competitive inhibitor of proto-oncogenic non-receptor tyrosine kinase(SRC)" but also a potent tubulin inhibitor (see microtubules below).

Tirbanibulin inhibits the SRC signaling pathway. Tyrosine kinase SRC, formerly known as C-SRC, (SRC=is the acronym for "cellular and sarcoma") is a tyrosine-protein kinase that is present associated with the cell membrane. SRC is a protooncogene and is considered the best studied protooncogene ever.

In cell-based experiments, tirbanibulin has been shown to induce tubulin depolymerization and cell cycle arrest in G2/M phase at low nanomolar concentrations. It acts similarly to colchicine (Niu L et al. 2019). Here, it reversibly binds to the colchicine binding site on β-tubulin, triggering a cellular effect (G2/M cell cycle arrest). The reversible binding of tirbanibulin explains its clinically low toxicity (Niu L et al. 2019).

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 comes in ointment form and is for topical use only.

Tirbanibulin ointment should be applied in a thin layer to the treatment area of up to 25 cm2 once daily on the face or scalp for a treatment cycle of five consecutive days. Approximately eight weeks after the start of treatment, the therapeutic effect can be assessed.

The treatment area should be cleaned with water and a mild soap before application and should then be dried. The ointment should then be squeezed from the disposable sachet onto a fingertip and applied in a thin layer evenly over the entire treatment area, up to a maximum of 25 cm2. It is recommended to apply the ointment daily at approximately the same time each day. The treated area should not be washed or touched for a period of about 8 hours.

Caution: Wash hands with soap and water before and immediately after applying the ointment!

• 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%)

Klisyri ^® 10 mg /g ointment

Tirbanibulin was approved for medical use in the United States in December 2020. It is the first representative of a new class of active substances (first in class) in this area of application. Approval for the European Union followed in July 2020.

1. S3 guideline Actinic keratosis and squamous cell carcinoma of the skin. AWMF guideline 032/022OL; March 2020.
2. Blauvelt A et al (2021) Phase 3 trials of tirbanibulin ointment for actinic keratosis. N Engl J Med 2021; 384: 512-20.
3. Klisyri (Almirall) package insert: https://image.wub service.uk/resources/static/des/210901/12/85/128549.pdf.

4. 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.