Peringatan Keamanan

The LD50 value of tirbanibulin has not been determined. While there is limited information on overdose from tirbanibulin, it may lead to an increase in the incidence and severity of local skin reactions.L27786

Tirbanibulin

DB06137

small molecule approved investigational

Deskripsi

Tirbanibulin (KX-O1 or KX2–391) is a dual inhibitor of Src Kinase and tubulin.A225726 On December 14, 2020, tirbanibulin was approved by the FDA for the topical treatment of actinic keratosis on the face or scalp. It is marketed under the brand name Klisyri.L27806 Actinic keratosis is a chronic condition characterized by lesions, which can potentially transform into invasive squamous cell carcinoma with a risk of 1% over 10 years.A225721,A225741 Tirbanibulin blocks the molecular pathways that promote the proliferation, survival, and metastasis of malignant cells. Tirbanibulin exhibits antitumour effects in vitro and in vivo A225791 and has been investigated for its antitumor efficacy in the management of various cancers, such as prostate cancer and breast cancer.A225726,A225731,A225736

Struktur Molekul 2D

Berat 431.536
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The half-life is about 4 hours.[A225736]
Volume Distribusi There is limited information on the volume of distribution of tirbanibulin. In mouse HT29 xenograft studies, the tissue to plasma ration of tirbanibulin was 1.52.[A225736]
Klirens (Clearance) There is limited information on the clearance rate of tirbanibulin.

Absorpsi

Tirbanibulin demonstrates good oral bioavailability.A225716 Following topical administration of doses ranging from 54 to 295 mg on the face or scalp, the steady-state concentration of tirbanibulin was achieved by 72 hours. At five days following initial administration, the mean Cmax was 0.34±0.30 ng/mL in subjects who received topical treatment on the face and 0.18±0.10 ng/mL in subjects who received topical treatment on the scalp. The mean AUC24 was 5.0±3.9 h x ng/mL in subjects who received topical treatment on the face and 3.2±1.9 h x ng/mL in subjects who received topical treatment on the scalp. The median Tmax was about seven hours.L27786

Metabolisme

In vitro, tirbanibulin is mainly metabolized by CYP3A4, and to a lesser extent, CYP2C8. In adult subjects with actinic keratosis, detected metabolites were KX2-5036 and KX2-5163, which were pharmacologically inactive metabolites with the highest plasma concentrations of 0.09 ng/mL and 0.12 ng/mL, respectively.L27786

Rute Eliminasi

There is limited information on the route of elimination of tirbanibulin.

Interaksi Obat

2 Data
Voriconazole The serum concentration of Tirbanibulin can be increased when it is combined with Voriconazole.
Etrasimod The risk or severity of immunosuppression can be increased when Tirbanibulin is combined with Etrasimod.

Target Protein

Tubulin beta chain TUBB
Proto-oncogene tyrosine-protein kinase Src SRC

Referensi & Sumber

Artikel (PubMed)
  • PMID: 33196758
    Kempers S, DuBois J, Forman S, Poon A, Cutler E, Wang H, Cutler D, Fang J, Kwan R: Tirbanibulin Ointment 1% as a Novel Treatment for Actinic Keratosis: Phase 1 and 2 Results. J Drugs Dermatol. 2020 Nov 1;19(11):1093-1100. doi: 10.36849/JDD.2020.5576.
  • PMID: 31628188
    Niu L, Yang J, Yan W, Yu Y, Zheng Y, Ye H, Chen Q, Chen L: Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of beta-tubulin explains KXO1's low clinical toxicity. J Biol Chem. 2019 Nov 29;294(48):18099-18108. doi: 10.1074/jbc.RA119.010732. Epub 2019 Oct 18.
  • PMID: 32067498
    Cramer P, Stockfleth E: Actinic keratosis: where do we stand and where is the future going to take us? Expert Opin Emerg Drugs. 2020 Mar;25(1):49-58. doi: 10.1080/14728214.2020.1730810. Epub 2020 Feb 20.
  • PMID: 22784709
    Anbalagan M, Ali A, Jones RK, Marsden CG, Sheng M, Carrier L, Bu Y, Hangauer D, Rowan BG: Peptidomimetic Src/pretubulin inhibitor KX-01 alone and in combination with paclitaxel suppresses growth, metastasis in human ER/PR/HER2-negative tumor xenografts. Mol Cancer Ther. 2012 Sep;11(9):1936-47. doi: 10.1158/1535-7163.MCT-12-0146. Epub 2012 Jul 10.
  • PMID: 21509526
    Anbalagan M, Carrier L, Glodowski S, Hangauer D, Shan B, Rowan BG: KX-01, a novel Src kinase inhibitor directed toward the peptide substrate site, synergizes with tamoxifen in estrogen receptor alpha positive breast cancer. Breast Cancer Res Treat. 2012 Apr;132(2):391-409. doi: 10.1007/s10549-011-1513-3. Epub 2011 Apr 21.
  • PMID: 23314737
    Antonarakis ES, Heath EI, Posadas EM, Yu EY, Harrison MR, Bruce JY, Cho SY, Wilding GE, Fetterly GJ, Hangauer DG, Kwan MF, Dyster LM, Carducci MA: A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer. Cancer Chemother Pharmacol. 2013 Apr;71(4):883-92. doi: 10.1007/s00280-013-2079-z. Epub 2013 Jan 13.
  • PMID: 24627245
    Dodds A, Chia A, Shumack S: Actinic keratosis: rationale and management. Dermatol Ther (Heidelb). 2014 Jun;4(1):11-31. doi: 10.1007/s13555-014-0049-y. Epub 2014 Mar 14.
  • PMID: 19060248
    Serrels B, Serrels A, Mason SM, Baldeschi C, Ashton GH, Canel M, Mackintosh LJ, Doyle B, Green TP, Frame MC, Sansom OJ, Brunton VG: A novel Src kinase inhibitor reduces tumour formation in a skin carcinogenesis model. Carcinogenesis. 2009 Feb;30(2):249-57. doi: 10.1093/carcin/bgn278. Epub 2008 Dec 5.
Menampilkan 8 dari 10 artikel.

Contoh Produk & Brand

Produk: 3 • International brands: 0
Produk
  • Klisyri
    Ointment • 10 mg/1g • Topical • US • Approved
  • Klisyri
    Ointment • 10 mg/g • Cutaneous • EU • Approved
  • Onakta
    Ointment • 1 % w/w • Topical • Canada • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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