Background
Phenotypic Drug Discovery (PD2)
PD2 Assay Module Descriptions
Endocrine/Cardiovascular – GLP-1 Secretion
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Endocrine/Cardiovascular – PCSK9 Synthesis Inhibition
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Autoimmune – IL-17 Secretion
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PD2 Assay Measures
GLP – 1 Secretion
Primary Assays
GLP-1 Secretion mSTC-1 SP / CRC ( % Stimulation) / (EC50)
GLP-1 Secretion hNCI CRC (EC50)
Cytolethality mSTC-1/hNCI LDH Secretion CRC (EC50)
GLP-1 Secretion Glu-Tag CRC (EC50)
Secondary assays
Growth Hormone Secretion Primary Rat Hepatocyte SP / CRC (% Stimulation / EC50)
Profiling Biochemical Activity - CSR Panel (Ki, % Efficacy) / PDE Profiling (IC50)
cAMP NCI (EC50)
Calcium Moblzn NCI (EC50)
PCSK9 Synthesis Inhibition
Primary assays
PCSK9 Secretion HepG2 SP / CRC (% Inhibition / IC50)
PCSK9 Secretion Cell Health HepG2 SP / CRC (% Inhibition / IC50)
Met Luciferase Reporter Assay CRC (IC50)
Secondary assays
PCSK9 ELISA HepG2 CRC (IC50)
ApoA-1 ELISA HepG2 CRC (IC50)
Profiling Biochemical Activity – Kinase Panel SP/CRC (%Efficacy / IC50)
Confirmatory Assays
GPCR Profiling (EC50)
IL-17 Secretion
Primary assays
IL-17 Secretion hPBMC SP (% Inhibition)
IL-17 Secretion hPBMC CRC (IC50)
Cytotox Cell Titer-Glo PBMC SP/CRC (% Inhibition / IC50)
IFNg Secretion hPBMC CRC (IC50)
IL-5 Secretion hPBMC CRC (IC50)
Secondary assays
hPGL3(LUC) Inhibition Promoter/Reporter Assays HEK293 CRC (IC50)
Profiling Biochemical and Cell-based Assays
SP= Single Point
CRC= Concentration Response Curve
PD2 Flow Schemes
Endocrine/Cardiovascular:
GLP-1 Secretion
Endocrine/Cardiovascular:
PCSK9 Synthesis Inhibition
Autoimmune:
IL-17 Secretion
GLP-1 Secretion
mSTC-1/hNCI
SP/CRC
PCSK9 Secretion/
Cell Health
HepG2
SP/CRC
IL-17 Secretion
hPBMC
SP/CRC
GLP-1 Secretion
mSTC-1/hNCI LDH
CRC
Met Luciferase Reporter
HepG2
Cytotox CTG
hPBMC
SP/CRC
CRC
IFNg / IL-5 Secretion
CRC
GLP-1 Secretion
Glu-Tag
CRC
Growth Hormone Secretion
Primary Rat Hepatocyte
SP/CRC
PCSK9/ApoA-1 ELISA
HepG2
CRC
Profiling Biochemical Activity
CSR Panel/PDE
Profiling Biochemical
Assays
Kinase Panel
SP/CRC
Promoter/Reporter Assays
hPGL3(LUC) Inhibition
HEK293
CRC
Profiling Biochemical
And Cell-based Assays
SP/CRC
cAMP
NCI
CRC
Ca2+ Mobilization
NCI
CRC
GPCR Profiling
(GPR119, GPR120, GPR40,
GPR41, GPR43 / TGR5)
CRC
SP= Single Point
CRC= Concentration Response Curve

CTP Centre Listing

Mn BID SHEET 6[2014-15]

PCSK9 Inhibition : From Genetics to Patients