Aplikasi teknik biomolekuler untuk validasi target obat PCSK9

1. Validasi PCSK9 sebagai
Target Obat pada
Dislipidemia-Aplikasi
Teknik Biomolekuler
dalam Farmakologi
LS by Lani Suryani

2. Target Obat — Molekul/Struktur Biologis
1 Terlibat dalam Patogenesis Penyakit
2 Memiliki Aksi Spesifik
3 Dapat Dimanipulasi oleh Agen Terapeutik
4 Memiliki Efek yang Dapat Diukur

3. Metode Farmakologi Molekuler dalam Pencarian
Target Obat

4. Keterlibatan PCSK9 dalam
Patogenesis Dislipidemia
1 Peran PCSK9 dalam Metabolisme
Lemak
2
Regulasi PCSK9 oleh SCAP&SREBP2

5. loss-of-function mutations
in PCSK9 – Extremely Low
LDL-C Plasma Level
PCSK9 associated
with degradation of
Hepatocyte LDL-R
2005
2004
2003
Discovery of
PCSK9 itself
2003
Gain-of-function
mutations in the PCSK9 gene -
Autosomal
dominant hypercholesterolemia
1 2 3 4

7. qRT-PCR
Immunoblotting
Immunoblotting
Mengkonfirmasi efek perbedaan tingkat ekspresi
gen PCSK9 pada tingkat protein (yaitu LDL-reseptor)
Real Time RT-PCR
Mengukur tingkat ekspresi gen PCSK9 pada level
mRNA

8. 1. Park SW, Moon YA, Horton JD. Post-transcriptional Regulation of Low Density Lipoprotein Receptor Protein by
Proprotein Convertase Subtilisin/Kexin Type 9a in Mouse Liver. J of Biological Chemistry 2004; 279(48):50630-
8
2. Bustin SA, Mueller R. Real-time Reverse Transcription PCR (qRT-PCR) and Its Potential Use in Clinical
Diagnosis. The Biochemical Society 2005; 109 : 365-379
3. Zheng et al. Therapeutic Targets : Progress of Their Exploration and Investigation of Their Characteristics.
Pharmacol Rev 2006;58:259–279
4. Urban D, et al. Targeting the Proprotein Convertase Subtilisin/Kexin Type 9 for the Treatment of Dyslipidemia
and Atherosclerosis. J of the Am Coll of Cardiology 2013; 62(16) : 1401-8
5. Chaudhary R et al. PCSK9 inhibitors: A new era of lipid lowering therapy. World J Cardiol 2017; 9(2): 76-91
6. Dickenson, J, et al. Molecular Pharmacology-from DNA to Drug Discovery. 2013. Oxford : A John Wiley &
Sons, Ltd
REFERENCES

9. Terima Kasih