MHS-MOLECULAR AND CELLULAR DRUG TARGETS -Nayyar.pdf Fundamentals of Medical Pharm (GMHS 711-01)MHS-MOLECULAR AND CELLULAR DRUG TARGETS

-large macromolecules

-much smaller molecules

specific binding sites

hydrophobic pockets

intermolecular forces

.What are the general characteristics of drug targets?

drug targets are

drugs are typically

drugs bind to

binding sites are often

binding involves

drug

target

3. What is the difference between binding groups and binding regions?

Answer:

• Binding groups → Functional groups on the ____ that interact with the target.

• Binding regions → Specific areas on the t______ that interact with the drug.

Receptors Ion Channels Enzymes Transporters

What are the four major classes of drug targets?

Answer:

macromolecule

5. What is a receptor?

Answer:
A receptor is a ___________(usually a protein) that binds a drug and initiates a biological response.

A. Cell Surface Receptors

Nuclear Receptors

6. What are the two major receptor locations?

A.______

• Located in plasma membrane

• Receive extracellular signals

• Transmit signals intracellularly

B. ________

• Located in cytosol or nucleus

• Bind lipid-soluble ligands

• Directly regulate gene transcription

• Steroid hormones

• Vitamin D

• Fatty acids

What types of molecules bind nuclear receptors?

• ________

• Vitamin A

• ________

• Xenobiotics

• _______

• Bile acids

endogenous ligand

What are orphan nuclear receptors?

Answer:
Receptors with no known _________ _______ (e.g., FXR, LXR, PPAR).
If a natural ligand is discovered, they become adopted orphan receptors.

activates

What is a receptor agonist?

Answer:
A drug that binds and ______ a receptor, producing a biological response.

Example:

• Morphine (opioid receptor agonist)

endogenous ligand

What is a receptor antagonist?

Answer:
A drug that binds but does not activate the receptor. It blocks ____ ______ binding.

Example:

• Losartan (angiotensin receptor blocker)

• DNA binding

• Gene transcription

How do nuclear receptor antagonists work?

Answer:
They prevent:

• Receptor activation

• _______

• _______

Example:

• Tamoxifen (estrogen receptor antagonist)

Ionotropic (Ligand-Gated Ion Channels)

Metabotropic (G-Protein Coupled Receptors)

Nuclear Receptors

Enzyme-Linked Receptors

What are the four types of receptors?

1. ___________

• Open/close ion channels directly

• Fast response

2._________

• Activate G-proteins

• Trigger second messenger cascades

• Slower but amplified response

3. __________

• Regulate gene transcription

4. _____________

• Have intrinsic enzyme activity (often tyrosine kinase)

• Trigger phosphorylation cascades

Metabotropic (GPCRs)

Which receptors use second messenger cascades?

Answer:

electrochemical gradient

What are ion channels?

Answer:
Membrane proteins that allow ions to move down their ______ ______.

• Channel blockers

• Modulators

How do drugs affect ion channels?

• __________ → physically block pore

• __________ → alter opening probability

• Channel openers → increase ion flow

Examples:

• Amlodipine (calcium channel blocker)

• Alprazolam (GABA-A chloride channel opener)

intracellular ion concentration.

What mediates effects of ion channel drugs?

Changes in

1. Competitive inhibition

1. Prodrug activation

How do drugs act on enzymes?

1. ___________

2. False substrate

3. ___________

therapeutic effect.

What happens when enzymes are inhibited?

Loss of product formation → ___________

• COX (enzyme)

Examples of enzyme inhibitors:

• Aspirin → inhibits __________

• Atorvastatin → inhibits HMG-CoA reductase

membrane-impermeable

What are transporters?

Proteins that move ___________ substances across membranes.

block solute movement

• inhibit serotonin reuptake

How do transporter inhibitors work?

They ____________→ alter intracellular concentrations.

• SSRIs →_______

• Loop diuretics → inhibit Na-K-2Cl symporter

• disrupts tubulin

Can drugs target structural proteins?

Yes.

Example:

• Vincristine → ________________

• Colchicine → inhibits microtubule polymerization

(DNA alkylation)

Can drugs target DNA?

Yes.

Example:

• Cyclophosphamide _____________

Short DNA fragments

What are antisense drugs?

____________ that bind mRNA and prevent translation.

Example:

• Fomivirsen

• Vitamins

• Minerals

• Amino acids

Can drugs act as nutrients?

Yes.

Examples (3):

vaccines

Can drugs act as antigens?

Yes.

Example:

Cyclooxygenase Inhibitors

___________ for pain relief,
particularly due to arthritis (aspirin; ibuprofen [Motrin ® ])

drug

Binding groups that are involved in binding interactions in
drug-target interactions are located on the…
A. drug
B. target
C. both drug and target

A

Binding sites in drug target interactions

A. area of a macromolecular target that is occupied by
a drug when it binds
B. region on the drug to which a drug target binds
C. functional groups used by a drug in binding to a drug
target
D. the bonds involved in binding a drug to its target

allosteric changes

Transporters

Some drugs bind to transporters and cause ___________
that prevent proper functioning of the transporters

D

Relief from pain by Aspirin results from prostaglandin
synthesis inhibition by cyclooxygenase (COX). Which of
the following is the aspirin (drug) target?

A. receptors
B. transporters
C. ion channels
D. enzymes

A

Famotidine, blocks the action of histamine in the parietal
cells in the stomach, ultimately blocking acid secretion in
the stomach. Which is the target of the drug Famotidine?

A. receptors
B. transporters
C. ion channels
D. enzymes
E. all of the above

A

Which one is a FALSE statement in an enzyme-linked
receptor interaction?

A. Receptor-enzyme interacts with an intracellular protein
called a "G-protein“
B. Three types of receptor-enzymes found in animals are 1)
receptor guanylate cyclases 2) receptor tyrosine kinases, and
3) receptor serine/threonine kinases.
C. The signal transduction pathways of receptor-enzymes
involve phosphorylation cascades.
D. A receptor-enzyme has an extracellular ligand-binding
domain, a transmembrane domain, and an intracellular
catalytic (enzyme) domain.

C

Which receptors are involved when neurotransmitter or
ligand binding to receptor leads to second messenger
cascade to affect its target cell.

A. Adrenergic
B. Cholinergic
C. Metabotropic
D. Ionotropic
E. Inhibitory

E

Receptors for transmembrane signaling

A. inotropic receptors
B. metabotropic receptors
C. enzyme-linked receptors
D. nuclear receptors
E. All of the above