Frequently Asked Questions (FAQ):

     Can IMPACT-F predict human oral bioavailability of entirely new molecules?

     Is IMPACT-F restricted to a specific therapeutic area, such as antivirals or cancer?

     What is required to predict oral bioavailability with IMPACT-F?

     At which stage of drug discovery and development should IMPACT-F be applied?

Question:

My company has discovered a new chemical entity (NCE) with a novel and unique mechanism of action. Up to now, no similar molecules have been investigated in human clinical trials. Can IMPACT-F predict human oral bioavailability of entirely new molecules?

Answer:  Yes. In cooperation with a pharmaceutical company, we have investigated this question. We have found that constantly good prediction results are obtained, regardless of whether highly similar compounds are present in PACT-F, the underlying knowledge base of IMPACT-F.

In fact, more than 82% of the investigated drug-candidates showed a maximal Tanimoto similarity below 0.67. This shows that highly similar drugs are not needed to reliably estimate the oral bioavailability of entirely novel drug structures. Please contact us if you are interested in the detailed report.

On the other hand, we found that small changes in molecular structure can dramatically influence the oral bioavailability of a drug candidate.

IMPACT-F uses and combines all available information in PACT-F from previous known bioavailability to create a reliable estimate of oral bioavailability in humans.

Question:

Is IMPACT-F restricted to a specific therapeutic area, such as antibiotics, cardiovascular drugs, or cancer therapeutics?

Answer:  No, there is no restriction on a specific therapeutic area. IMPACT-F can predict the oral bioavailability of small-molecule drug-candidates ranging across all therapeutic areas.

We have evaluated IMPACT-F with drugs and drug-candidates from all therapeutic areas, such as cardiovascular, cancer, gastrointestinal, pain, antivirals, antibacterials, inflammation, anticoagulants, antiepileptic drugs, Alzheimer’s and Parkinson’s disease, renal diseases, Multiple Sclerosis, respiratory diseases, antidiabetic agents, COPD, asthma, rheumatoid arthritis, obesity, metabolic disorders, central nervous system disorders. Reliable prediction results were achieved in all cases, so there is no restriction to a specific therapeutic area.

IMPACT-F has been used by pharmaceutical companies in different therapeutic areas (cancer, diabetes, inflammation, autoimmune diseases, antivirals) for selection and prioritisation of drug candidates, to optimise prodrugs and to evaluate oral bioavailability before advanced clinical trials in humans, see recent collaborations.

Question:

What is required to predict oral bioavailability with IMPACT-F (in vivo PK in rats, measured logP)?

Answer:  The structure of the drug-candidate and time to do the calculations, that’s all.

Eight years ago, our aim was to create an expert system which was not dependent on additional experimental input parameters. They take time to generate, different conditions in measurement cannot always be unified, and chemical synthesis is expensive and takes time as well.

The chemical structure of an investigational compound is available at a very early time in drug discovery projects, even before chemical synthesis and preclinical experiments can take place. If the decision to develop a compound further can be made at the earliest possibility, then more money and time can be saved and resources can be concentrated on the most prospective ones.

In drug discovery it is important to identify useful drug candidates at the earliest opportunity. A large amount of time and money is spent on candidates which will never come to market.

Low oral bioavailability in clinical trials is one of the main reasons why clinical trials fail.

Question:

At which stage of drug discovery and development should IMPACT-F be applied?

Answer: The earlier the better! Many drug-candidates fail in clinical trials due to low oral bioavailability in humans. As a result billions of Euros are wasted every year on drug-candidates which never reach the market. IMPACT-F identifies these failures and substantially reduces drug development costs and time involved.

IMPACT-F has now been used by several pharmaceutical companies, even though the technology was launched only a few months ago.

Up to now, the expert system was applied in different phases of drug discovery and development. On the one hand within the preclinical discovery phase to optimise and select drug candidates with high oral bioavailability. On the other hand IMPACT-F has estimated the oral bioavailability of drug-candidates which are scheduled for clinical trials in humans.

Read current press release: Pharma uses IMPACT-F to predict drug efficacy
 

Further explanations and abbreviations:

Lead optimization (LO):
Drug discovery often starts from initial hits with pharmacological activity. Structural modifications of compound structure yield to optimised leads. They can proceed to drug candidates, which are further investigated in clinical trials in humans.

Quantitative structure activity relationship (QSAR):
Chemical structures are set in relation to their biological activity.

Absorption & distribution & metabolism & excretion (ADME):
Oral bioavailability combines both absorption and metabolism

Quantitative structure property relationship (QSPR):
Oral bioavailability is a main property of leads and drug candidates.

 

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