Lead Identification

Chapter
Part of the Topics in Medicinal Chemistry book series (TMC, volume 5)

Abstract

High quality leads provide the foundation for the discovery of successful clinical development candidates, and therefore the identification of leads is an essential part of drug discovery. Many factors contribute to the quality of a lead, including biological, physicochemical, ADME, and PK parameters. The identification of high quality leads, which are needed for successful lead optimization, requires the optimization of all of these parameters. Parallel optimization of all parameters is the most efficient way to achieve the goal of lead identification.

Keywords

Hit Lead Pharmacokinetics Physicochemical 

Abbreviations

β-Amyloid

AcpS

Acyl carrier protein synthase

AD

Alzheimer's disease

ADME

Absorption distribution metabolism excretion

AGP

Alpha glycoprotein

APP

Amyloid precursor protein

BBB

Blood brain barrier

BBB PAMPA

Blood brain barrier parallel artificial membrane permeability assay

BSA

Bovine serum albumin

CCR1

Chemokine (C-C motif) receptor 1

CDK2

Cyclin-dependent kinase 2

CGRP

Calcitonin gene related peptide

CHK-1

Checkpoint kinase 1

CLint

Intrinsic clearance

COST

Changing one separate factor at a time

cPLA2α

Cytosolic phospholipase A2α

CYP450

Cytochrome P450

DMSO

Dimethyl sulfoxide

DPP-4

Dipeptidyl peptidase IV

FACS

Fluorescence activated cell sorter

FLIPR

Fluorimetric imaging plate reader

GLP-1

Glucagon-like peptide-1

GPCR

G-protein coupled receptor

HCV

Hepatitis C virus

hERG

Human ether-a-go-go-related gene

HLM

Human liver microsomes

HMQC

Heteronuclear multiple quantum correlation

HSA

Human serum albumin

HTS

High throughput screen

IKKβ

IκB kinase-β

IP

Intellectual property

ITK

Interleukin-2-inducible T cell kinase

iv

Intravenous

LC/MS

Liquid chromatography/mass spectrometry

LE

Ligand efficiency

MCH1

Melanin-concentrating hormone 1

MIC

Minimum inhibitory concentration

MVA

Multivariate data analysis

MW

Molecular weight

NHR

Nuclear hormone receptor

NLM

Nonlinear mapping

PAMPA

Parallel artificial membrane permeability assay

PCA

Principal component analysis

PDE5

Phosphodiesterase 5

PGP

P-Glycoprotein

PK

Pharmacokinetic

PKCθ

Protein kinase C θ

PLS

Projection to latent structures by means of a partial least squares analysis

po

Oral

PSA

Polar surface area

RARβ2

Retinoic acid β2

RLM

Rat liver microsomes

SAR

Structure activity relationship

SPR

Structure property relationship

SPR

Surface plasmon resonance

STD

Saturation transfer difference

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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Medicinal ChemistryWyeth ResearchPearl RiverUSA

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