Of the thousands of compounds active against a target, how many typically pass preclinical testing?

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BlackTom AI · Accepted Answer

Question restatement: The prompt asks, among thousands of compounds active against a target, how many typically pass preclinical testing?

Option a. 10–50: This range is higher than commonly cited preclinical pass rates, which are a small fraction of the initial pool. It overstates the progression from discovery to preclinical success.

Option b. 1–5: This range aligns with typical screening-to-preclinical success stories in drug discovery, where only a handful of compounds out of thousands advance due to factors like efficacy, selectivity, toxicity, and pharmacokinetics. It reflects the very selective bottleneck at preclinical advancement.

Option c. 5–10: While closer to reality than some ranges, this still represents a larger fraction than is commonly observed; the attrition rate is very steep, and 5–10 out of thousands would be unusually optimistic given typical discovery pipeline challenges.

Option d. 50-100: This option vastly overestimates the number that survive preclinical testing from a large initial pool; advancing 50–100 compounds would imply a much higher success rate through preclinical screening than is generally observed, given safety, efficacy, and ADME/Tox hurdles.

Why the correct option is correct (b): In early drug discovery, many compounds are identified, but only a tiny subset demonstrates the required potency, selectivity, safety, and drug-like properties to proceed to preclinical studies. The typical attrition rate at this stage is high, often yielding only about a dozen or fewer candidates per thousands initially identified, with 1–5 being a common, cautious estimate of those that advance.

Why the other options are incorrect (a, c, d):
- a incorrect because it overestimates the number that pass to preclinical testing, not accounting for stringent safety and efficacy filters.
- c incorrect since it still overestimates progression likelihood relative to the steep drop-off seen in preclinical qualification.
- d incorrect because it grossly overstates the viable pool remaining after initial screening, contradicting common industry experience of tight selection for preclinical progression.

In summary, option b reflects the widely acknowledged reality that only a small handful of compounds out of thousands advance past preclinical testing due to rigorous requirements across efficacy, safety, and pharmacokinetic criteria.

Of the thousands of compounds active against a target, how many typically pass preclinical testing?

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