This document summarizes key transporters involved in drug absorption and disposition: - Apical sodium dependent bile acid transporter (ASBT) transports bile acids and drug analogs to assist intestinal absorption, with a pharmacophore model revealing requirements of one hydrogen bond donor, one acceptor, one negative charge, and three hydrophobic centers. - Organic cation transporters (OCTs) facilitate uptake of cationic drugs in various tissues, with a human OCT1 model suggesting requirements of three hydrophobic features and one positive ionizable feature. - Organic anion transporting polypeptides (OATPs) influence drug plasma concentrations by transporting substrates in multiple tissues, with an OATP1B1 model identifying hydrophobic

1. Presentedby
MISS.JYOTIDIPAKMHOPREKAR
M Pharmacy(FirstYear,SemIi)
RollNo. 06
DEPARTMENTOF PHARMACEUTICS
SHREESANTKRUPACOLLEGEOF PHARMACYGHOGAON.

2. Human Apical Sodium Dependent Bile Acid Transporter
(ASBT)
The human apical sodium dependent bile acid transporter (ASBT)
is a high efficacy, high capacity transporter expressed on the apical
membrane of intestinal epithelial cells and cholangiocytes.
It assists absorption of bile acids and their analogs, thus providing
an additional intestinal target for improving drug absorption.
Baringhaus and colleagues developed a pharmacophore model
based on a training set of 17 chemically diverse inhibitors of ASBT.

3. The model revealed ASBT transport requirement as one hydrogen
bond donor, one hydrogen bond acceptor, one negative charge, and
three hydrophobic centers.
It is mainly expressed in intestine and kidney, affecting drug
absorption and excretion.

5. Organic Cation Transporter
(OCT)
OCT facilitate the uptake of many cationic drugs across many
different barrier membranes from kidney, liver and intestine
epithelia.
A broad range of drugs or their metabolites fall into the chemical
class of organic cation (carrying a net positive charge at
physiological pH) including Antiarrhythmics, β adrenoreceptor
blocking agents, antihistamines, antiviral agents and skelatal
muscle relaxing agents.

6. Three OCTs have been cloned from different species, OCT1, OCT2
and OCT3.
A human OCT1 pharmacophore model was developed by analyzing
the extent of inhibition of TEA uptake in HeLa cells of 22diverse
molecules.
The model suggest the transport requirements of human OCT1 as three
hydrophobic features and one positive ionizable feature.
Molecular determinants of substrate binding to human OCT2 and
rabbit OCT2 .
Both 2D and 3D QSAR analyses were performed to identify and
discriminate the binding requirements of the two orthologs.
This work illustrates the sensitivity of in silico modeling in
discriminating similar transporters.

11. Organic Anion Transporting Polypeptide
(OATPs)
Influence the plasma concentration of many drugs by actively
transporting them across a diverse range of tissue membranes such
as liver, intestine, lung and brain.
Because of their broad substrate specificity OATPs transport not
only organic anionic drugs as a originally thought but also organic
cationic drugs.
Currently 11 human OATPs have been identified, and the
substrate binding requirements of the best studied OATP1B1 were
successfully modeled with the metapharmacophore approach.
 Assessing a training set of 18 diverse molecules, the
metapharmacophore model identified three hydrophobic features
flanked by two hydrogen bond acceptor features to be the essential
requirement for OATP1B1 transport.