Review Abemaciclib: Senyawa Inhibitor Cyclin-Dependent Kinase 4, Generasi Ketiga Obat Kanker Payudara

https://doi.org/10.22146/jpmmpi.v2i1.68253

Viviane Annisa(1*)

(1) Fakultas Farmasi, Universitas Gadjah Mada
(*) Corresponding Author

Abstract


Abemaciclib merupakan inhibitor CDK generasi ketiga sebagai obat kanker payudara. Mekanisme aksi Abemaciclib dengan menghambat Cyclin-dependent kinase 4 (CDK4) dan 6 (CDK6) pada ikatan ATP dari CDK4 dan CDK6. Generasi pertama inhibitor CDK tidak selektif terhadap CKD4 dan CDK6 yang memiliki toksisitas yang sangat tinggi serta efikasi yang rendah, contohnya: Flavopiridol, Seliciclib, Dinaciclib, dan Milciclin, sedangkan generasi kedua didesain agar lebih selektif terhadap CDK2 dan CDK4, namun masih memiliki masalah toksisitas, contohnya: Dinaciclib. Generasi ketiga menunjukkan selektifitas yang lebih tinggi dibandingkan dengan generasi sebelumnya dan dapat meningkatkan efektivitas serta menurunkan efek sampingnya, contohnya: Abemaciclib, Ribociclib, dan Palbociclib. Jika dibandingkan dengan Palbociclib dan Ribociclib, Abemaciclib memiliki selektivitas yang lebih tinggi pada CDK4. Studi awal tentang Structur-Activity Relationship (SAR) dari derivat amina diheteroaromatik sebagai inhibitor CDK4/6 menunjukkan bahwa amino pyrimidine dan amino pyridine berperan menjaga aktivitas enzimatik dan seluler. Analog tetrahydronaphthyridine didesain untuk meningkatkan farmakokinetik dari Abemaciclib yang lebih baik. Atom deuterium (D) yang memiliki posisi berbeda dapat menambah stabilitas metabolik Abemaciclib. Terjadi peningkatan 11-45% terhadap stabilitas metabolik yang ditunjukkan dengan nilai waktu paruh (t1/2) yang lebih tinggi.

Kata kunci : Abemaciclib; Inhibitor CDK4; Inhibitor CDK6; SAR




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DOI: https://doi.org/10.22146/jpmmpi.v2i1.68253

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Jurnal ini diterbitkan oleh:

Bidang Jurnal Paradigma Himpunan Mahasiswa Pascasarjana (HMP UGM) Universitas Gadjah Mada

69PF+FWC, Pogung Kidul, Pogung Kidul, Sinduadi, Kec. Mlati, Kabupaten Sleman, Daerah Istimewa Yogyakarta, Indonesia

Dengan dukungan dari:

Direktorat Kemahasiswaan Universitas Gadjah Mada
Gedung Pusat UGM, Lantai 1 Sayap Utara, Bulaksumur, Yogyakarta, Indonesia