Dr. Yudi Wicaksono, S.Si., Apt., M.Si.

Steps in Prodrug Design

 Identification of drug delivery problem

 Identification of desired physicochemical properties

 Selection of transport moiety which will give prodrug

desired transport properties be readily cleaved in the
desired biological compartment
 Classification of Prodrugs
 Based on therapeutic categories
 Based on the site of conversion
 Based on the structure
Classification based on therapeutic categories
 Anticancer prodrugs
 Antiviral prodrugs
 Antibacterial prodrugs
 Nonsteroidal anti-inflammatory
prodrugs
 Cardiovascular prodrugs
Classification based on the site of conversion
*ADEP/GDEP/VDEP = antibody-, gene- or virus-directed enzyme prodrugs
Classification based on the structure

A.Carrier linked prodrug (Bipartite,

Tripartite, and Mutual Prodrugs)

B. Bioprecursors
A. Carrier linked prodrug
 Carrier linked prodrug consists of the attachment of a
carrier group to the active drug to alter its physicochemical
properties.

The subsequent enzymatic or non-enzymatic mechanism

releases the active drug moiety.
Carrier linked prodrug :
A1. Bipartite prodrug
A.2 Tripartite prodrug
 The carrier group is attached via linker to
drug.
A.3 Mutual prodrugs
 A mutual prodrug consists of two pharmacologically
active agents coupled together so that each acts as a
promoiety for the other agent and vice versa.
 A mutual prodrug is a bipartite or tripartite prodrug in
which the carrier is a synergistic drug with the drug to
which it is linked.
 Ex. : Benorylate is a mutual prodrug aspirin and
paracetamol.
Mutual prodrug:
B. Bioprecursors
 Bioprecursor prodrugs produce their effects after in
vivo chemical modification of their inactive form.
 Bioprecursor prodrugs rely on oxidative or reductive
activation reactions unlike the hydrolytic activation of
carrier-linked prodrugs.
 They metabolized into a new compound that may
itself be active or further metabolized to an active
metabolite.
Bioprecursors