Tirbanibulin

Tirbanibulin, sold under the brand name Klisyri, is a medication for the treatment of actinic keratosis (AKs) on the face or scalp.[1][2][3]

Tirbanibulin
Clinical data
Trade namesKlisyri
Other namesKX2-391
License data
Routes of
administration		Topical
Drug classMicrotubule inhibitor
ATC code
Legal status
Legal status
Identifiers
IUPAC name
  • N-benzyl-2-[5-[4-(2-morpholin-4-ylethoxy)phenyl]pyridin-2-yl]acetamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.305.161
Chemical and physical data
FormulaC26H29N3O3
Molar mass431.536 g·mol−1
3D model (JSmol)
SMILES
  • O=C(Cc1ccc(-c2ccc(OCCN3CCOCC3)cc2)cn1)NCc1ccccc1
InChI
  • InChI=1S/C26H29N3O3/c30-26(28-19-21-4-2-1-3-5-21)18-24-9-6-23(20-27-24)22-7-10-25(11-8-22)32-17-14-29-12-15-31-16-13-29/h1-11,20H,12-19H2,(H,28,30)
  • Key:HUNGUWOZPQBXGX-UHFFFAOYSA-N

The most common side effects include local skin reactions, application site pruritus, and application site pain.[1][2]

Tirbanibulin was approved for medical use in the United States in December 2020,[2][4][5] and in the European Union in July 2021.[3] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[6]

It functions as a mitotic inhibitor by inhibiting tubulin polymerization and Src kinase signaling[7] can be potentially effective in deferring the development of AKs to squamous cell carcinoma in situ.[8]

Medical uses

Tirbanibulin is indicated for the topical treatment of actinic keratosis of the face or scalp.[1][2][3]

Mechanism of Action

Tirbanibulin, chemically known as N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl) pyridine-2-yl) acetamide, is a microtubule and non–ATP-competitive inhibitor.[8] The drug in various ways mimics the mechanisms of chemotherapy[9] by suspending the protooncogenic Src tyrosine kinase signaling pathway. Notably, it promotes G2/M arrest during cell cycle, upregulates p53, and triggers apoptosis via caspase-3 stimulation and poly (ADP-ribose) polymerase cleavage.[8]

Side effects

In several studies tirbanibulin has been observed to induce skin reactions at the site of application, ranging from mild to severe erythema, flaking, ulceration, and pain.[9]

As of now, there has been no extensive research conducted on the risks of tirbanibulin usage by specific human populations (i.e., pregnant populations). There also has been no significant differences observed in safety or effectiveness of the drug between geriatric or pediatric populations.[10]

History

The U.S. Food and Drug Administration (FDA) approved tirbanibulin based on evidence from two clinical trials (Trial 1/ NCT03285477 and Trial 2/NCT03285490) of 702 adults with actinic keratosis on the face or scalp.[2] The trials were conducted at 62 sites in the United States.[2] Participants received once daily treatment with either tirbanibulin or inactive control ointment for 5 consecutive days to the single predetermined area where they had actinic keratosis.[2] Neither the participants nor the health care providers knew which treatment was being given until after the trial was completed.[2] The benefit of tirbanibulin in comparison to control was assessed after 57 days by comparing the percentage of participants who did not have any actinic keratosis on the treatment area (100% clearance).[2]

Society and culture

On 20 May 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for tirbanibulin, intended for the treatment of actinic keratosis.[11] The applicant for this medicinal product is Almirall, S.A. Tirbanibulin was approved for medical use in the European Union in July 2021.[3]

References
  1. "Klisyri- tirbanibulin ointment". DailyMed. Retrieved 8 January 2021.
  2. "Drug Trials Snapshot: Klisyri". U.S. Food and Drug Administration (FDA). 14 December 2020. Retrieved 8 January 2021. This article incorporates text from this source, which is in the public domain.
  3. "Klisyri EPAR". European Medicines Agency (EMA). Retrieved 22 July 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  4. "Drug Approval Package: Klisyri". U.S. Food and Drug Administration (FDA). 28 December 2020. Retrieved 8 January 2021.
  5. "Athenex Announces FDA Approval of Klisyri (Tirbanibulin) for the Treatment of Actinic Keratosis on the Face or Scalp" (Press release). Athenex Inc. 15 December 2020. Retrieved 15 December 2020 – via GlobeNewswire.
  6. "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Retrieved 17 January 2021.
  7. Niu L, Yang J, Yan W, Yu Y, Zheng Y, Ye H, et al. (November 2019). "Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of β-tubulin explains KXO1's low clinical toxicity". The Journal of Biological Chemistry. 294 (48): 18099–18108. doi:10.1074/jbc.RA119.010732. PMC 6885616. PMID 31628188.
  8. Dao, Diem-Phuong D.; Sahni, Vikram Nath; Sahni, Dev Ram; Balogh, Esther A.; Grada, Ayman; Feldman, Steven R. (April 2022). "1% Tirbanibulin Ointment for the Treatment of Actinic Keratoses". Annals of Pharmacotherapy. 56 (4): 494–500. doi:10.1177/10600280211031329. ISSN 1060-0280. PMC 8899810. PMID 34301153.
  9. Geer, Kamini (1 November 2021). "Tirbanibulin (Klisyri) for the Treatment of Actinic Keratosis". American Family Physician. 104 (5): 519–521. PMID 34783508.
  10. "Tirbanibulin". American Journal of Health-System Pharmacy. 78 (8): 656–657. 31 March 2021. doi:10.1093/ajhp/zxab094. ISSN 1079-2082. PMID 33787828.
  11. "Klisyri: Pending EC decision". European Medicines Agency. 21 May 2021. Retrieved 23 May 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  • "Tirbanibulin". Drug Information Portal. U.S. National Library of Medicine.
  • Clinical trial number NCT03285477 for "A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on AK on Face or Scalp (AK003)" at ClinicalTrials.gov
  • Clinical trial number NCT03285490 for "A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on AK on Face or Scalp (AK004)" at ClinicalTrials.gov
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