Drug-likeness screening and filters MCQs With Answer

Drug-likeness screening and filters MCQs With Answer

Drug-likeness screening evaluates physicochemical and ADME-related properties to prioritize compounds during lead discovery. Key concepts include Lipinski’s Rule of Five, Veber and Ghose filters, Rule of Three for fragments, TPSA, logP, H-bond donors/acceptors, rotatable bonds, PAINS/REOS filters and in silico tools (SwissADME, pkCSM) for predicting bioavailability, permeability, metabolism and toxicity. Understanding these descriptors and filter limitations helps B. Pharm students apply rational lead optimization and avoid false positives. This short, focused set emphasizes practical interpretation of descriptors, oral bioavailability, BBB penetration and filter trade-offs. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which of the following is a Lipinski Rule of Five criterion?

• Molecular weight ≤ 500
• Polar surface area ≤ 140 Ų
• Rotatable bonds ≤ 3
• Fragment molecular weight ≤ 300

Correct Answer: Molecular weight ≤ 500

Q2. Which two descriptors are central to Veber’s rule for oral bioavailability?

• TPSA and number of rotatable bonds
• Molecular weight and clogP
• H-bond donors and aromatic rings
• Molar refractivity and atom count

Correct Answer: TPSA and number of rotatable bonds

Q3. What is the maximum molecular weight recommended by the Rule of Three for fragment libraries?

• ≤ 300
• ≤ 500
• ≤ 150
• ≤ 400

Correct Answer: ≤ 300

Q4. Which TPSA value is commonly associated with good oral absorption according to screening heuristics?

• ≤ 140 Ų
• ≥ 200 Ų
• ≤ 60 Ų
• ≥ 140 Ų

Correct Answer: ≤ 140 Ų

Q5. Which filter is designed to flag frequent hitters and assay-interfering compounds?

• PAINS
• Veber
• Ghose
• Lipinski

Correct Answer: PAINS

Q6. Which descriptor belongs to the Ghose filter criteria?

• Molar refractivity between 40 and 130
• TPSA ≤ 60 Ų
• Rotatable bonds ≤ 3
• H-bond donors ≤ 1

Correct Answer: Molar refractivity between 40 and 130

Q7. Which property directly measures compound lipophilicity?

• logP
• TPSA
• Rotatable bonds
• Molar refractivity

Correct Answer: logP

Q8. High topological polar surface area (TPSA) most directly predicts:

• Poor membrane permeability
• High lipophilicity
• Increased metabolic stability
• Better oral bioavailability

Correct Answer: Poor membrane permeability

Q9. A compound that is a P-glycoprotein substrate is likely to experience which effect?

• Efflux from cells, reducing absorption
• Improved blood–brain barrier penetration
• Increased passive diffusion
• Enhanced oral bioavailability

Correct Answer: Efflux from cells, reducing absorption

Q10. A molecule has MW 520, logP 4, HBD 2 and HBA 8. Which Lipinski rule does it violate?

• Molecular weight ≤ 500
• Aliphatic ring count ≤ 3
• H-bond acceptors ≤ 5
• Rotatable bonds ≤ 10

Correct Answer: Molecular weight ≤ 500

Q11. Which descriptor is commonly used to predict blood–brain barrier penetration when low?

• TPSA < 90 Ų
• Molecular weight > 600
• H-bond donors > 5
• Rotatable bonds > 15

Correct Answer: TPSA < 90 Ų

Q12. Which online tool is widely used for rapid drug-likeness and ADME prediction?

• SwissADME
• BLAST
• PyMOL
• MEGA

Correct Answer: SwissADME

Q13. A commonly used bioavailability score threshold indicating reasonable oral availability is:

• 0.55
• 0.10
• 0.99
• 0.01

Correct Answer: 0.55

Q14. According to Veber, the maximum recommended number of rotatable bonds for good oral absorption is:

• 10
• 3
• 20
• 0

Correct Answer: 10

Q15. Increasing which property generally decreases aqueous solubility?

• logP
• TPSA
• H-bond donors
• Number of ionizable groups

Correct Answer: logP

Q16. A limitation of rigid rule-based filters (e.g., Lipinski) is that they can:

• Discard bioactive natural products and complex scaffolds
• Predict CYP isoform selectivity with high accuracy
• Guarantee clinical success for compliant compounds
• Eliminate the need for ADME testing

Correct Answer: Discard bioactive natural products and complex scaffolds

Q17. Which descriptor, when increased (higher fraction), indicates greater three-dimensionality and often better clinical outcomes?

• Fraction sp3 (Fsp3)
• Aromatic ring count
• Number of planar heterocycles
• Number of rotamers

Correct Answer: Fraction sp3 (Fsp3)

Q18. Which molecular weight range is commonly used to define lead-like compounds?

• 250–350
• 500–700
• 50–150
• 400–600

Correct Answer: 250–350

Q19. Which experimental assay is commonly used to assess metabolic stability in early screening?

• Human liver microsomal stability assay
• CBC blood count
• ELISA for protein binding
• Western blot for CYP expression

Correct Answer: Human liver microsomal stability assay

Q20. PAINS filters are primarily intended to remove compounds that are:

• Promiscuous assay interferers or frequent hitters
• Too polar for oral absorption
• Below fragment size limits
• Ideal drug candidates

Correct Answer: Promiscuous assay interferers or frequent hitters

Q21. Which term is NOT part of ADME?

• Pharmacodynamics
• Absorption
• Distribution
• Excretion

Correct Answer: Pharmacodynamics

Q22. Which descriptor counts hydrogen bond donors in a molecule?

• H-bond donors
• H-bond acceptors
• TPSA
• Atom count

Correct Answer: H-bond donors

Q23. Which rule is specifically tailored for fragment-based drug discovery?

• Rule of Three
• Lipinski Rule of Five
• Veber rule
• Ghose filter

Correct Answer: Rule of Three

Q24. To reduce first-pass hepatic metabolism, a desirable property is:

• High metabolic stability (low clearance)
• Very high lipophilicity (logP > 7)
• High number of reactive electrophiles
• Large polar surface area (> 200 Ų)

Correct Answer: High metabolic stability (low clearance)

Q25. Which computed metric is most commonly reported to quantify lipophilicity?

• cLogP
• TPSA
• H-bond donor count
• Rotatable bond count

Correct Answer: cLogP

Q26. Which filter or rule is intended to flag chemically reactive or promiscuous substructures beyond PAINS?

• REOS (Rapid Elimination Of Swill)
• Veber rule
• Rule of Three
• Lipinski Rule of Five

Correct Answer: REOS (Rapid Elimination Of Swill)

Q27. Which descriptor counts the number of hydrogen bond acceptors?

• H-bond acceptors
• H-bond donors
• LogP
• Fraction sp3

Correct Answer: H-bond acceptors

Q28. Which in vitro assay is used to estimate intestinal permeability?

• Caco-2 cell permeability assay
• Western blot assay
• Flow cytometry for apoptosis
• ELISA for cytokines

Correct Answer: Caco-2 cell permeability assay

Q29. Which property typically increases the likelihood of passive cellular uptake?

• Low polar surface area
• High TPSA (> 200 Ų)
• Very high H-bond donor count
• High number of rotatable bonds (> 20)

Correct Answer: Low polar surface area

Q30. Which statement best describes drug-likeness rules and filters?

• They are useful guidelines but not absolute rules
• They guarantee clinical efficacy if followed strictly
• They replace the need for any experimental ADME testing
• They only apply to injectable drugs

Correct Answer: They are useful guidelines but not absolute rules

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