Abstract
Drug discovery remains a complex and iterative process accompanied with a high failure rate. Before compounds enter the clinic, failures can be due to (1) an inability to demonstrate that the target can modulate the disease in a preclinical model, (2) the lack of a therapeutic index to modulate the target safely or (3) the inability to find molecules with the right balance of properties such as potency, selectivity, ADME properties, safety endpoints, etc. Moreover, drug discovery is geting harder because of the pursuit of targets that are deemed ‘undruggable’. What makes a target ‘undruggable’ is usually the lack of a distinct binding pocket that is unique. Two fundamental approaches to drug discovery exist: structure-based design and property-based design. In this chapter we capture the molecular properties that influence and drive drug discovery. In addition, for each class of drugs we captured their distinct properties.
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Abbreviations
- 5-HMT:
-
5-hydroxymethyl tolterodine
- ABT:
-
1-aminobenzotriazole
- AI:
-
Artificial intelligence
- ALK:
-
Anaplastic lymphoma kinase
- AO:
-
Aldehyde oxidase
- API :
-
Active pharmaceutical ingredient
- ATP:
-
Adenosine triphosphate
- BCS :
-
Biopharmaceutics Classification System
- BDDCS :
-
Biopharmaceutics Drug Disposition Classification System
- BMO:
-
Biomimetic metalloporphyrin oxidation
- CI :
-
Covalent inhibitor (also known as covalent modifiers)
- CL:
-
Clearance
- CNS :
-
Central nervous system
- CYP :
-
Cytochrome P450
- ECCS :
-
Extended Clearance Classification System
- EM:
-
Electron microscopy
- FaSSIF:
-
Fasted state simulated intestinal fluid
- FeSSIF:
-
Fed state simulated intestinal fluid
- FMO:
-
Flavin-containing monooxygenase
- GPCR:
-
G protein-coupled receptor
- HAT:
-
Hydrogen atom abstraction
- HBA:
-
Hydrogen bond accepter
- HBD:
-
Hydrogen bond donor
- ID:
-
Infectious diseases
- IV:
-
Intravenous administration
- IVIVC:
-
in vitro – in vivo correlation
- KIE:
-
Kinetic isotope effect
- LipE:
-
Lipophilic efficiency
- LLE:
-
Lipophilic ligand efficiency
- logD:
-
Distribution coefficient
- logP:
-
Partition coefficient
- MD:
-
Metabolic diseases
- MPO :
-
Multi-parameter optimization
- MW:
-
Molecular weight
- NAR:
-
Number of aromatic rings
- NMR:
-
Nuclear magnetic resonance
- NRB:
-
Number of rotatable bonds
- NVP :
-
Nevirapine
- ONC:
-
Oncology
- PDB:
-
Protein data bank
- P-gp:
-
P-glycoprotein
- PK :
-
Pharmacokinetics
- PO :
-
Oral administration
- PPi:
-
Protein-protein interaction
- PSA:
-
Polar surface area
- Ro5:
-
Rule of 5; Lipinski’s rule
- SET:
-
Topological single electron transfer
- TPSA:
-
Topological polar surface area
- UGT:
-
Glucuronosyltransferase
- Vd:
-
Volume of distribution
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Khojasteh, S.C., Wong, H., Zhang, D., Hop, C.E. (2022). Drug Properties. In: Discovery DMPK Quick Guide. Springer, Cham. https://doi.org/10.1007/978-3-031-10691-0_2
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