Podcast
Questions and Answers
Which intermolecular force is generally the strongest contributor to drug-target interactions for small molecule drugs?
Which intermolecular force is generally the strongest contributor to drug-target interactions for small molecule drugs?
- Van der Waals
- Electrostatic (correct)
- Hydrophobic
- Hydrogen bonding
A medicinal chemist is optimizing a small molecule drug for improved binding affinity. Which strategy would likely yield the MOST significant improvement?
A medicinal chemist is optimizing a small molecule drug for improved binding affinity. Which strategy would likely yield the MOST significant improvement?
- Enhancing electrostatic interactions with the target. (correct)
- Minimizing the hydrophobic surface area of the molecule.
- Increasing the number of rotatable bonds in the molecule.
- Decreasing the molecule's molecular weight.
A drug candidate has a molecular weight of 650 Da and relies primarily on hydrophobic interactions for binding. What is the MOST probable way improvement can be made?
A drug candidate has a molecular weight of 650 Da and relies primarily on hydrophobic interactions for binding. What is the MOST probable way improvement can be made?
- Replace a methyl group with a hydroxyl group to increase hydrophobic interactions.
- Decrease the number of hydrogen bond donors to improve membrane permeability.
- Introduce a charged group to increase electrostatic interactions. (correct)
- Increase the molecule's overall size to fill the binding pocket more completely.
A novel drug is designed to inhibit a protein-protein interaction. Which of the following intermolecular forces would be MOST critical to optimize for potent binding?
A novel drug is designed to inhibit a protein-protein interaction. Which of the following intermolecular forces would be MOST critical to optimize for potent binding?
What does the partition coefficient describe?
What does the partition coefficient describe?
A compound exhibits a partition coefficient (logP) of 3.5. What does this value suggest about the compound's properties?
A compound exhibits a partition coefficient (logP) of 3.5. What does this value suggest about the compound's properties?
A drug is designed with a very high partition coefficient. What is a possible challenge?
A drug is designed with a very high partition coefficient. What is a possible challenge?
A series of compounds are synthesized with varying substituents and the same base structure. How should the effect of these substituents on the partition coefficient be determined?
A series of compounds are synthesized with varying substituents and the same base structure. How should the effect of these substituents on the partition coefficient be determined?
For small molecule drugs, what is the typical upper limit of molecular weight?
For small molecule drugs, what is the typical upper limit of molecular weight?
A small molecule drug candidate needs to be optimized for oral bioavailability. How do you achieve this goal?
A small molecule drug candidate needs to be optimized for oral bioavailability. How do you achieve this goal?
Which of the interactions is MOST impacted with a mutation in the active site?
Which of the interactions is MOST impacted with a mutation in the active site?
How does the addition of a fluorine atom can affect a molecule?
How does the addition of a fluorine atom can affect a molecule?
Which characteristics influence the strength of hydrogen bonds in drug-target interactions?
Which characteristics influence the strength of hydrogen bonds in drug-target interactions?
A drug is to selectively bind to a specific protein isoform over other closely related isoforms. Design a drug that targets the isofrom's properties.
A drug is to selectively bind to a specific protein isoform over other closely related isoforms. Design a drug that targets the isofrom's properties.
What role do Van der Waals forces play in drug-target binding?
What role do Van der Waals forces play in drug-target binding?
A series of drugs is designed to target the active site of an enzyme. Which molecular characteristics would optimize selectivity?
A series of drugs is designed to target the active site of an enzyme. Which molecular characteristics would optimize selectivity?
If a drug has poor membrane permeability due to excessive hydrogen bond donors, which of the following strategies is likely to improve its cell penetration?
If a drug has poor membrane permeability due to excessive hydrogen bond donors, which of the following strategies is likely to improve its cell penetration?
How do you use LogP values to predict drug distribution?
How do you use LogP values to predict drug distribution?
What is the impact of high lipophilicity on drug metabolism?
What is the impact of high lipophilicity on drug metabolism?
How does electrostatic interactions impact drug selectivity?
How does electrostatic interactions impact drug selectivity?
What is the impact of including “halogen bonding” to bind to a target?
What is the impact of including “halogen bonding” to bind to a target?
What is the importance of hydrophobic interactions in drug design?
What is the importance of hydrophobic interactions in drug design?
Aromatic rings can be added to drugs to do the following EXCEPT:
Aromatic rings can be added to drugs to do the following EXCEPT:
Which of the following applies to hydrogen bond strength?
Which of the following applies to hydrogen bond strength?
Which of the following actions will increase the likelihood of the molecule crossing the blood brain barrier?
Which of the following actions will increase the likelihood of the molecule crossing the blood brain barrier?
What is the effect on partition coefficient if a drug contains a permanently ionized group at physiological pH?
What is the effect on partition coefficient if a drug contains a permanently ionized group at physiological pH?
What is the impact of high polar surface area in a drug?
What is the impact of high polar surface area in a drug?
When designing a salt bridge between a drug and its target, which of the following pairings would maximize the electrostatic interaction?
When designing a salt bridge between a drug and its target, which of the following pairings would maximize the electrostatic interaction?
What potential advantages can the introduction of a chiral center into a drug molecule provide?
What potential advantages can the introduction of a chiral center into a drug molecule provide?
You want to design a prodrug to improve drug properties. Which of these approaches is most suitable?
You want to design a prodrug to improve drug properties. Which of these approaches is most suitable?
What is a common strategy to improve the oral bioavailability of a poorly absorbed drug?
What is a common strategy to improve the oral bioavailability of a poorly absorbed drug?
How would one identify the key structural components responsible for bioactivity?
How would one identify the key structural components responsible for bioactivity?
Assuming similar binding affinity, how do you increase the in vivo potency?
Assuming similar binding affinity, how do you increase the in vivo potency?
Considering the various intermolecular forces present in drug-receptor interactions, which one is MOST affected by changes in pH?
Considering the various intermolecular forces present in drug-receptor interactions, which one is MOST affected by changes in pH?
When designing a drug, which strategy would likely result in a molecule with increased aqueous solubility?
When designing a drug, which strategy would likely result in a molecule with increased aqueous solubility?
How to balance drug properties?
How to balance drug properties?
What property of van der Waals forces makes them significant in drug design?
What property of van der Waals forces makes them significant in drug design?
What role does entropy play?
What role does entropy play?
Of Electrostatic, Hydrophobic, Hydrogen bonding, and Van der Waals, which of the following interactions are the SHORTEST?
Of Electrostatic, Hydrophobic, Hydrogen bonding, and Van der Waals, which of the following interactions are the SHORTEST?
A new drug molecule shows great promise in vitro, but has poor oral bioavailability because it gets pumped out. What to do?
A new drug molecule shows great promise in vitro, but has poor oral bioavailability because it gets pumped out. What to do?
When optimizing a lead compound, which intermolecular force generally contributes the LEAST to the overall binding energy in drug-target interactions?
When optimizing a lead compound, which intermolecular force generally contributes the LEAST to the overall binding energy in drug-target interactions?
A drug candidate shows good binding affinity but has a short duration of action due to rapid metabolism. Which modification is LEAST likely to extend its duration of action?
A drug candidate shows good binding affinity but has a short duration of action due to rapid metabolism. Which modification is LEAST likely to extend its duration of action?
A drug is designed to target a shallow, hydrophobic pocket on a protein surface. Which structural modification would MOST likely increase its binding affinity?
A drug is designed to target a shallow, hydrophobic pocket on a protein surface. Which structural modification would MOST likely increase its binding affinity?
A drug candidate is highly potent in vitro but shows poor efficacy in vivo due to extensive plasma protein binding. Which strategy is MOST likely to improve its in vivo efficacy?
A drug candidate is highly potent in vitro but shows poor efficacy in vivo due to extensive plasma protein binding. Which strategy is MOST likely to improve its in vivo efficacy?
Which of the following methods would be the MOST reliable for determining a compound's partition coefficient?
Which of the following methods would be the MOST reliable for determining a compound's partition coefficient?
A compound has a logP value of -1.5. What does this value suggest about the compound's solubility and permeability?
A compound has a logP value of -1.5. What does this value suggest about the compound's solubility and permeability?
A drug exhibits a very high partition coefficient, resulting in accumulation in fatty tissues. What is a likely consequence of this?
A drug exhibits a very high partition coefficient, resulting in accumulation in fatty tissues. What is a likely consequence of this?
During lead optimization, you synthesize a series of analogs and want to assess the impact of different substituents on the octanol-water partition coefficient. What is the MOST appropriate experimental technique?
During lead optimization, you synthesize a series of analogs and want to assess the impact of different substituents on the octanol-water partition coefficient. What is the MOST appropriate experimental technique?
A research team is conducting a structure-activity relationship (SAR) study on a series of compounds. They discover that increasing the size of a substituent on an aromatic ring consistently improves binding affinity. What is a plausible explanation for this observation?
A research team is conducting a structure-activity relationship (SAR) study on a series of compounds. They discover that increasing the size of a substituent on an aromatic ring consistently improves binding affinity. What is a plausible explanation for this observation?
A new drug candidate exhibits excellent target affinity but extremely poor oral bioavailability. Its structure contains several polar functional groups and a high molecular weight (over 700 Da). What is the MOST likely reason for the poor bioavailability?
A new drug candidate exhibits excellent target affinity but extremely poor oral bioavailability. Its structure contains several polar functional groups and a high molecular weight (over 700 Da). What is the MOST likely reason for the poor bioavailability?
You are trying to improve the selectivity of a drug for a specific protein target. Which of these strategies can improve selectivity?
You are trying to improve the selectivity of a drug for a specific protein target. Which of these strategies can improve selectivity?
Which of the following is NOT a common effect of introducing a fluorine atom into a drug molecule?
Which of the following is NOT a common effect of introducing a fluorine atom into a drug molecule?
What is the role of induced fit in drug-target binding?
What is the role of induced fit in drug-target binding?
A library of compounds is screened, and a hit compound is identified that inhibits the target enzyme. It has a good ligand efficiency but only moderate affinity. What strategy would be suitable to improve the compound?
A library of compounds is screened, and a hit compound is identified that inhibits the target enzyme. It has a good ligand efficiency but only moderate affinity. What strategy would be suitable to improve the compound?
A drug is highly metabolized by CYP3A4 in the liver, leading to low oral bioavailability. Which of the following structural modifications would be LEAST likely to reduce CYP3A4 metabolism?
A drug is highly metabolized by CYP3A4 in the liver, leading to low oral bioavailability. Which of the following structural modifications would be LEAST likely to reduce CYP3A4 metabolism?
A research group is developing a new drug that needs to cross the blood-brain barrier (BBB). Which of the following modifications would be MOST likely to improve its BBB permeability?
A research group is developing a new drug that needs to cross the blood-brain barrier (BBB). Which of the following modifications would be MOST likely to improve its BBB permeability?
A drug molecule contains a carboxylic acid group (pKa ~ 4.5). How will its ionization state change as it moves from the stomach (pH ~ 2) to the small intestine (pH ~ 6)?
A drug molecule contains a carboxylic acid group (pKa ~ 4.5). How will its ionization state change as it moves from the stomach (pH ~ 2) to the small intestine (pH ~ 6)?
Which of the following strategies is LEAST likely to improve the aqueous solubility of a highly lipophilic drug candidate?
Which of the following strategies is LEAST likely to improve the aqueous solubility of a highly lipophilic drug candidate?
A drug is found to bind to its target with high affinity but dissociates rapidly, leading to a short duration of action. How can we change this?
A drug is found to bind to its target with high affinity but dissociates rapidly, leading to a short duration of action. How can we change this?
What is the primary difference between a drug molecule that acts as a competitive inhibitor and one that acts as an allosteric modulator?
What is the primary difference between a drug molecule that acts as a competitive inhibitor and one that acts as an allosteric modulator?
A lead compound shows good activity against a target enzyme, but suffers from poor ligand efficiency (LE). Which of the following strategies would be most appropriate to improve the LE?
A lead compound shows good activity against a target enzyme, but suffers from poor ligand efficiency (LE). Which of the following strategies would be most appropriate to improve the LE?
You are designing a drug to target a protein with a highly flexible binding pocket. Which consideration would MOST influence your design?
You are designing a drug to target a protein with a highly flexible binding pocket. Which consideration would MOST influence your design?
A new drug lead is discovered, and it features a weakly basic amine (pKa ~ 6.5). At a physiological pH of 7.4, what is the approximate ratio of the ionized (protonated) form to the non-ionized form?
A new drug lead is discovered, and it features a weakly basic amine (pKa ~ 6.5). At a physiological pH of 7.4, what is the approximate ratio of the ionized (protonated) form to the non-ionized form?
A medicinal chemist is tasked with improving the oral bioavailability of a highly lipophilic drug. Which is MOST likely to be effective?
A medicinal chemist is tasked with improving the oral bioavailability of a highly lipophilic drug. Which is MOST likely to be effective?
You are designing a new drug intended to target a receptor located within the brain. Which strategy would LEAST assist?
You are designing a new drug intended to target a receptor located within the brain. Which strategy would LEAST assist?
Of the following, which strategy is LEAST likely to improve the binding affinity of a drug by exploiting entropy?
Of the following, which strategy is LEAST likely to improve the binding affinity of a drug by exploiting entropy?
When designing a drug to inhibit a protein-protein interaction (PPI), which factor is commonly the MOST challenging?
When designing a drug to inhibit a protein-protein interaction (PPI), which factor is commonly the MOST challenging?
What is the key difference between pharmacokinetics (PK) and pharmacodynamics (PD)?
What is the key difference between pharmacokinetics (PK) and pharmacodynamics (PD)?
A drug has a chiral center, but the marketed drug product is a racemate. What is the MOST likely reason?
A drug has a chiral center, but the marketed drug product is a racemate. What is the MOST likely reason?
A new drug is discovered to be a substrate for a specific efflux transporter in the gut, limiting its oral absorption. Which strategy is MOST likely to improve its oral bioavailability?
A new drug is discovered to be a substrate for a specific efflux transporter in the gut, limiting its oral absorption. Which strategy is MOST likely to improve its oral bioavailability?
A drug shows good in vitro activity but is rapidly glucuronidated in vivo, leading to inactivation and elimination. Which structural modification would be LEAST likely to prevent glucuronidation?
A drug shows good in vitro activity but is rapidly glucuronidated in vivo, leading to inactivation and elimination. Which structural modification would be LEAST likely to prevent glucuronidation?
You want to design a drug that selectively inhibits one isozyme of an enzyme family but not others. What is the MOST important consideration?
You want to design a drug that selectively inhibits one isozyme of an enzyme family but not others. What is the MOST important consideration?
Which of the following intermolecular forces is MOST sensitive to changes in the distance between the drug and its target?
Which of the following intermolecular forces is MOST sensitive to changes in the distance between the drug and its target?
A fragment-based drug discovery campaign identifies two fragments that bind to adjacent sites in the target protein with weak affinity. What is the next logical step?
A fragment-based drug discovery campaign identifies two fragments that bind to adjacent sites in the target protein with weak affinity. What is the next logical step?
A lead compound shows promising activity but also inhibits a closely related off-target protein, leading to side effects. What is the best strategy?
A lead compound shows promising activity but also inhibits a closely related off-target protein, leading to side effects. What is the best strategy?
Which of the following properties of a drug molecule is LEAST likely to affect its volume of distribution (Vd)?
Which of the following properties of a drug molecule is LEAST likely to affect its volume of distribution (Vd)?
Based on your knowledge of intermolecular forces, select from the forces listed the STRONGEST contributing factor?
Based on your knowledge of intermolecular forces, select from the forces listed the STRONGEST contributing factor?
Which intermolecular force generally contributes the most to drug-target interactions for small molecule drugs?
Which intermolecular force generally contributes the most to drug-target interactions for small molecule drugs?
How does the partition coefficient (logP) relate to a drug's ability to cross cell membranes?
How does the partition coefficient (logP) relate to a drug's ability to cross cell membranes?
A medicinal chemist aims to modify a lead compound to increase its partition coefficient without significantly altering its molecular weight. Which strategy would be most effective?
A medicinal chemist aims to modify a lead compound to increase its partition coefficient without significantly altering its molecular weight. Which strategy would be most effective?
A drug is designed to target a protein-protein interaction by mimicking a key binding motif. Which intermolecular force would be MOST critical to optimize for potent and selective binding?
A drug is designed to target a protein-protein interaction by mimicking a key binding motif. Which intermolecular force would be MOST critical to optimize for potent and selective binding?
How can the strategic placement of halogen atoms within a drug molecule affect its binding affinity and selectivity?
How can the strategic placement of halogen atoms within a drug molecule affect its binding affinity and selectivity?
In the early stages of drug discovery, a series of compounds with varying logP values are synthesized. What is the best approach to determine the optimal range for further development?
In the early stages of drug discovery, a series of compounds with varying logP values are synthesized. What is the best approach to determine the optimal range for further development?
A potential drug candidate has a high molecular weight and numerous hydrogen bond donors. What is a likely consequence of these properties regarding its oral bioavailability?
A potential drug candidate has a high molecular weight and numerous hydrogen bond donors. What is a likely consequence of these properties regarding its oral bioavailability?
A drug is developed to bind to a specific receptor subtype. What strategy is most likely to improve the drug's selectivity profile?
A drug is developed to bind to a specific receptor subtype. What strategy is most likely to improve the drug's selectivity profile?
How does the presence of aromatic rings in a drug molecule influence its overall properties and interactions?
How does the presence of aromatic rings in a drug molecule influence its overall properties and interactions?
A medicinal chemist aims to improve the aqueous solubility of a highly lipophilic drug candidate without significantly altering its binding affinity. Which approach is most likely to succeed?
A medicinal chemist aims to improve the aqueous solubility of a highly lipophilic drug candidate without significantly altering its binding affinity. Which approach is most likely to succeed?
What is the primary purpose of determining a compound's partition coefficient during drug development?
What is the primary purpose of determining a compound's partition coefficient during drug development?
A novel drug candidate exhibits a very low partition coefficient. What challenges might be expected for this compound?
A novel drug candidate exhibits a very low partition coefficient. What challenges might be expected for this compound?
During lead optimization, a series of analogs is synthesized and logP values are experimentally measured. What is the MOST appropriate method for measuring logP of a small molecule?
During lead optimization, a series of analogs is synthesized and logP values are experimentally measured. What is the MOST appropriate method for measuring logP of a small molecule?
A drug is found to have a logP value greater than 5. What is a likely challenge associated with this high lipophilicity?
A drug is found to have a logP value greater than 5. What is a likely challenge associated with this high lipophilicity?
To enhance drug potency, a medicinal chemist decides to optimize van der Waals interactions between a drug and its target. What approach would BEST achieve this?
To enhance drug potency, a medicinal chemist decides to optimize van der Waals interactions between a drug and its target. What approach would BEST achieve this?
A drug with a poor logP value (too low) is being investigated. What structural modification is most likely to improve its membrane permeability?
A drug with a poor logP value (too low) is being investigated. What structural modification is most likely to improve its membrane permeability?
What properties do Electrostatic interactions depend on?
What properties do Electrostatic interactions depend on?
How does the strength of hydrogen bonds relate to drug-target interactions when compared to Van der Waals forces?
How does the strength of hydrogen bonds relate to drug-target interactions when compared to Van der Waals forces?
Which change to a molecule is most likely to increase its partition coefficient?
Which change to a molecule is most likely to increase its partition coefficient?
A new drug is developed, what logP range would optimize the chance that a drug crosses a membrane to reach its target?
A new drug is developed, what logP range would optimize the chance that a drug crosses a membrane to reach its target?
Flashcards
Small Molecule Drugs MW
Small Molecule Drugs MW
Molecular Weight
What is Partition Coefficient?
What is Partition Coefficient?
Describes the extent to which an uncharged compound dissolves in an aqueous solvent versus organic solvent
Study Notes
- Small molecule drugs molecular weight (MW) interactions consist of:
- Electrostatic forces
- Hydrophobic forces
- Hydrogen bonding
- Van der Waals forces
- Partition Coefficient describes the extent to which an uncharged compound dissolves in an aqueous solvent versus an organic solvent.
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Description
Molecular interactions of small molecule drugs involve electrostatic, hydrophobic, hydrogen bonding, and Van der Waals forces. The partition coefficient indicates how the drug dissolves in aqueous versus organic solvents.
