This seminar discusses computer aided drug development with a focus on efflux transporters that impact drug absorption and distribution. It describes the roles of P-glycoprotein (P-gp), Breast Cancer Resistance Protein (BCRP), and nucleoside transporters. P-gp and BCRP are ATP-dependent efflux pumps that transport various substrates out of cells, reducing drug absorption and enhancing excretion. Inhibition of these pumps can improve drug delivery. Nucleoside transporters also transport natural and synthetic nucleoside drugs and impact their disposition. Understanding these transporters through computer modeling can help optimize drug properties.

1. SEMINAR ON
SUBJECT: COMPUTER AIDED DRUG DEVELOPMENT
SUBMITTED BY: SUBMITTED TO:
PUSHPA SAHANI Prof K MAHALINGAN
2nd SEM M. Pharm Department of Pharmaceutics

2. CONTENT
Introduction
Active Transport
P-gp
BCRP
Nucleoside Transport

5. P-GP
• P-glycoprotein (p-gp) is an ATP-dependent effl ux
transporter that transports a broad range of substrates
out the cell.
• It affects drug disposition by reducing absorption and
enhancing renal and hepatic excretion.
• For example, P-gp is known to limit the intestinal
absorption of the anticancer drug paclitaxel and
restricts the CNS penetration of human
immunodeficiency virus (HIV) protease inhibitors.
• It also responsible for multidrug resistance in cancer
chemotherapy.

7. Inhibition of P-gp
• The inhibition of efflux pump is mainly done
in order to improve the delivery of therpeutic
agents.
• In general P-gp can be inhibited by 2
mechanism
1. Blocking drug binding site either
competively or non competively.
2.interfering with ATP

8. BCRP
• Breast cancer resistance protein
• It is an another ATP dependent efflux transport
• It confers resistance to a variety of anticancer
agents anthracyclins
• In addition to high level of experession in
hematological and solid tumors BCRP is
expressed in intestine,liver and brain thus
implicating is very complicated role in drug
disposition behaviour

9. Nucleoside Transporter
• It transport both naturally occuring nucleoside
and synthetic analogs that are used as
anticancer drugs and viral drugs.
• There are various type of nucleoside
transporter including concentrative nucleoside
transporter (CNT1 CNT2 CNT3) &
equilibrative nucleoside transporter (ENT1
ENT2 ENT3).
• Each have different substrate specificity.

10. • It have broad affinity, low selectivity & are
ubiquitously located.
• CNT have high affinity, selective located in
epittelia of intestive kidney, liver & brain,
indicating their involvement in drug disposition,
distribution & excretion.
• The first 3D, QSAR model for nucleoside
transporter was generated back in 1190.
• All model show the common features required for
nucleoside transporter mediated transport:
2 hydrophobic features & one hydrogen bond
acceptor on the pentose ring.

11. References
Computer application in pharmaceutical
research and development, by sean Ekins
published by john wiley and sons inc.
http://crdd.osdd.net/admet.php
https://en.wikipedia.org/wiki
httpps://www.solvobiotech.com/transporters/bc
rp