Drug Discovery Today  Volume 24, Number 3  March 2019 REVIEWS

Reviews  INFORMATICS
Artificial intelligence in drug
development: present status and
future prospects
Kit-Kay Mak1,2 and Mallikarjuna Rao Pichika2,3
1
School of Postgraduate Studies and Research, International Medical University, Kuala Lumpur, Malaysia
2
Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
3
Head, Centre for Bioactive Molecules and Drug Delivery, Institute for Research, Development and Innovation (IRDI), International Medical University, Kuala
Lumpur, Malaysia

Artificial intelligence (AI) uses personified knowledge and learns from the solutions it produces to
address not only specific but also complex problems. Remarkable improvements in computational
power coupled with advancements in AI technology could be utilised to revolutionise the drug
development process. At present, the pharmaceutical industry is facing challenges in sustaining their
drug development programmes because of increased R&D costs and reduced efficiency. In this review, we
discuss the major causes of attrition rates in new drug approvals, the possible ways that AI can improve
the efficiency of the drug development process and collaboration of pharmaceutical industry giants with
AI-powered drug discovery firms.

Introduction
Artificial intelligence (AI) is the simulation of the human intelli-
gence process by computers. The process includes acquiring infor-
mation, developing rules for using the information, drawing
approximate or definite conclusions and self-correction. The ad-
vancement of AI can be seen as a double-edged sword: many fear
that it will threaten their employment; by contrast, every advance
in AI is celebrated because of the belief that it will vastly contribute
to the betterment of society. AI is used in various sectors from
innovating educational methods to automating business process-
es. The sprouting idea of adopting AI in the drug development
process has shifted from hype to hope. In this review, the possible
applications of AI in the drug development pipeline in drug
development strategies and processes, the pharmaceutical R&D
efficiency and attrition, and partnerships between AI and phar-
maceutical companies are discussed.
AI, machine learning and deep learning
The incorporation of AI into the healthcare industry is concisely
shown in Fig. 1. AI is described as the use of techniques that enable
computers to mimic human behaviour (Fig. 1). AI also contains a
Corresponding author: Pichika, M.R. (mallikarjunarao@imu.edu.my)
subfield called machine learning (ML), which uses statistical meth-
ods with the ability to learn with or without being explicitly
programmed [1–3]. ML is categorised into supervised, unsuper-
vised and reinforcement learning. Supervised learning comprises
classification and regression methods where the predictive model
is developed based upon the data from input and output sources.
Output from supervised ML entails disease diagnosis under the
subgroup classification; and drug efficacy and ADMET prediction
under the subgroup regression [4]. Unsupervised learning com-
prises clustering and feature-finding methods by grouping and
interpreting data based solely on input data [5]. Through unsu-
pervised ML, outputs such as disease subtype discovery from
clustering and disease target discovery from feature-finding meth-
ods can be attained [6]. Reinforcement learning is largely driven by
decision making in a given environment and its execution to
maximise its performance. The outputs from this type of ML
include de novo drug design under decision making and experi-
mental designs under execution – where both can be achieved via
modelling and quantum chemistry [7]. A further subfield of ML
called deep learning (DL) uses artificial neural networks that adapt
and learn from the vast amount of experimental data [3,8]. The big
data and associated data mining and algorithm methods could
provide us with the capacity to discover new compounds that

1359-6446/ã 2018 Elsevier Ltd. All rights reserved.

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 REVIEWS Drug Discovery Today  Volume 24, Number 3  March 2019

Any technique which enables computers to mimic human brain.

It is simply a data analysis method that automates analytical model building using
Research
algorithms that iteratively learn from data. Computers can identify hidden insights
Wearables without being explicitly programmed.
Artificial inteligence

Drug discovery

Machine learning
Disease It is a deeper
Virtual Classification
Reviews  INFORMATICS

diagnosis
assistant Supervised subset of AI that
learning processes data

Deep learning
Drug
Healthcare

Patient data &

Regression efficacy/ADMET and creates
risk analysis

Machine learning
prediction patterns for
Hospital decision making
Disease subtype
management Clustering
Unsupervised
discovery purposes. It
Mental health learning comprises
Disease target
Feature finding networks which
discovery
Surgery are capable of
De novo drug learning from
Decision making
Lifestyle Reinforcement design
unstructured
learning
Digital health Experimental date.
Execution
monitoring & design
diagnostics

Drug Discovery Today

FIGURE 1
The applications of artificial intelligence (AI) and its subfields: machine learning and deep learning, in healthcare.

could potentially be new drugs, uncover or repurpose drugs that specific enzyme or with an entire organism. The first compound
could be more potent when used individually or in combination that shows activity against a given biological target is called a ‘hit’.
and improve the area of personalised medicine based on genetic Hits are often found during the screening of chemical libraries,
markers. The emergence of DL was observed with the increasing computer simulation or screening of naturally isolated materials,
amount of data and the continuous growth of computer power. such as plants, bacteria and fungi [13]. The identification of a lead
The striking difference that makes DL a subfield of AI is the molecule is the second step in drug development. A lead is a
flexibility in the architecture of neural networks such as convolu- chemical compound that shows promising potential that can lead
tional neural network (CNNs), recurrent neural networks (RNNs) to the development of a new drug as a treatment for a disease.
and fully connected feed-forward networks [7]. It is believed, with Identified hits are screened in cell-based assays predictive of the
proper establishment of methods in AI, we will witness the transi- disease state and in animal models of disease to characterise the
tion into an era of minimised failures in clinical trials and a faster, efficacy of the compound and its probable safety profile. Once a
cheaper and effective drug development processes [9–11]. lead compound has been found, its chemical structure is used as a
starting point for chemical modifications with the objective of
Drug development process discovering compounds with maximal therapeutic benefit and
The feedback-driven drug development process starts from exist- minimal potential for harm [13,14].
ing results obtained from various sources such as high-throughput During the process of lead generation, hit molecules are sys-
compound and fragment screening, computational modelling and tematically modified to improve their activity and selectivity
information available in the literature. This process alternates towards specific biological targets, while reducing toxicity and
between induction and deduction. This inductive–deductive cycle unwanted effects. The chemically related compounds derived
eventually leads to optimised hit and lead compounds. Automa- from a hit are called analogues and the process is referred to as
tion of specific parts of the cycle reduces randomness and errors hit expansion [15]. Medicinal chemists undertake hit expansion
and improves the efficiency of drug development. De novo design using well-established organic chemistry techniques. To increase
methods require knowledge of organic chemistry for in silico the synthetic throughput, chemists focus on a specific reaction or
compound synthesis and virtual screening models that function set of reactions to assemble building blocks together to make a
as surrogates for biochemical and biological tests of efficacy and series of analogues quickly. A ‘building block’ is a compound that
toxicity [12]. Ultimately, active learning algorithms allow the possesses a reactive functional group and atoms that interact with
identification of new or novel compounds with promising activi- the active site of a biological target. This active site is a specific
ties against a given disease target. region in the biological target to which the compound (or sub-
The first step in drug development is the identification of novel strate) binds through interaction forces. The binding of a substrate
chemical compounds with biological activity. This biological ac- to an active site can be visualised as ‘lock and key’ or ‘induced-fit’
tivity can arise from the interaction of the compound with a models [14,16].

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Drug Discovery Today  Volume 24, Number 3  March 2019
R&D efficiency and attrition rate in drug development
Well-established drug-likeness guidelines in drug development are
strictly applied, yet pharmaceutical companies face considerable
challenges in improving R&D efficiency. The R&D efficiency is
simply a term used to describe the number of new drugs approved
by the FDA per billion US$ spent on R&D alone. The cost of
discovering and developing a drug has since escalated from US$
800 million in the year 2001 to the current estimated figure of US$
3 billion. The cost for drug development includes the entirety of
failure; thus the estimated cost is an average estimate for a new
drug to be introduced into the clinic [17]. The declining rate in the
numbers of new drugs approved per billion US$ spent on R&D is
alarming. Thus, Scannell et al. systematically analysed the primary
causes for such worrying statistics, and narrowed them down to
four factors impacting the R&D inefficiency: (i) the ‘better than
Beatles’ problem; (ii) the ‘cautious regulator’ problem; (iii) the
‘throw money at it’ tendency; and (iv) ‘basic-research–brute-force’
bias [18].
The better than Beatles factor offers an analogy that describes
the improbable idea of developing a new drug for a particular
disease with pharmacological activity better than any of the
existing approved drugs. The hurdles explained here concern
the fate of every new drug that offers a better therapeutic effect.
With every new drug, the stakes are raised, and the R&D ineffi-
ciency takes place here as it becomes more and more difficult to
clear the ever-progressing hurdles. Cautious regulators describe
the increase in stringency and in the tightening of regulations
owing to drug misfortunes in the past. It is a progressive effort to
lower the risk tolerance in new drugs and to create a guide for
drugs with safer profiles, which is appropriate for the consumers
but considerably increases R&D expenditure. This is followed by
the throw money at it tendency, an inclination where R&D
facilities increase their recruitment in human and other resources
in the hopes of getting good returns on investment by being the
first to launch a new drug. This also contributes to their high R&D
expenditures. Lastly, basic-research–brute-force bias refers to
overestimating the ability of advances in basic research – espe-
cially target identification and validation and brute-force screen-
ing methods in preclinical research – to increase the success rate
in the clinical stages of drug development [18]. In addition, it is
known that the therapeutic benefits of drugs arise from the
interactions with multiple proteins rather than a single protein.
Thus, it is challenging to design a drug that acts on multiple
targets [19]. Another theory proposed to explain the decline in
R&D efficiency is the ‘low-hanging fruit’ problem. This describes
the fate of different tractable drug targets. The drugs for easily
tractable drug targets were already invented and that leaves us
with the more difficult drug targets. Despite the exciting chal-
lenge for discovery, attempts to develop new drugs will require a
higher cost in R&D [20].
The increase in R&D costs as well as high attrition rates in the
development process of a new drug pose challenges to the phar-
maceutical industry. The underlying causes and possible measures
to reduce attrition rates have previously been reviewed [21,22].
The rate of attrition was described using first-in-human trials to
register ten established pharma companies in the period 1991–
2000, where the regular success rate of products that make it
through development and approval from the regulators is nearly
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11% (i.e., one in nine compounds). Nearly 62% of new chemical
entities (NCEs) in Phase IIb and Phase III clinical trials do not reach
the clinic. The major underlying sources of attrition in late clinical
stages are attributed to clinical safety and efficacy followed by
formulation, pharmacokinetics and bioavailability, and toxicity.
The lack of efficacy that emerged in therapeutic areas with high
Phase IIb and Phase III failure rates includes drugs for central
nervous systems (CNS) and oncology applications, mainly owing
Reviews  INFORMATICS
to the lack of available fit-for-purpose animal models [23] in
preclinical development. Additionally, another contributing fac-
tor for attrition is the ‘narrow clinical research’ strategy adopted by
pharmaceutical companies. This term refers to the extensive use of
in vitro and in silico models instead of animal models in the early
stages of the drug development process. The opportunities for
serendipitous discovery are also limited with the existing system
because the current system considers a drug candidate that exerts
other pharmacological effects than the intended effect as a clinical
trial failure. Furthermore, multicentre clinical trials across the
globe are also preferred with the goal of obtaining diverse data
[24]. However, this leads to thinly spread patients (smaller pools of
samples) in which the doctors can miss out on the opportunity to
observe new pharmacological effects. By contrast, the clinical trial
size for a new follow-up drug in any therapeutic area is relatively
high. This is because the follow-up drug should be more potent
than the existing drugs for it to be eligible for registration with the
FDA. As per the guidelines, the clinical trial size must be inversely
proportional to the square of the difference in the dose. For
instance, if the dose is halved the clinical trial size must be
increased four times [25]. All these constraints contribute to an
increase in cost of later-stage clinical trials.
The return on R&D investment is reduced by the availability of
many treatment options for a given disease, resulting in the low
probability of making a new follow-up drug as a blockbuster drug.
Additionally, the long cycle time for approval owing to the strin-
gent approval rules stipulated by the FDA also acts as a contribut-
ing factor for a decline in return on R&D investments. However,
these factors are not universal as supported by the scientific
literature that demonstrates that different therapeutic areas have
different rates of success. For example, biologics have a higher rate
of success from first-in-human studies to the clinic, and licensing-
in compounds [21] has relatively higher success rates, at 24%.
The rate of attrition of compounds with novel mechanisms of
action is higher than that of those with precedent mechanisms of
action. Pharma companies can average out the different therapeu-
tic areas of varying success rates as a measure to balance the overall
success to reduce the attrition rates [26]. Thus, by understanding
their respective underlying factors, the attrition rates could be
reduced.
Applications of AI in drug development
The tasks of finding successful new drugs is daunting and predom-
inantly the most difficult part of drug development. This is caused
by the vast size of what is known as chemical space, which is
estimated to be in the order of 1060 molecules [27]. The technolo-
gies that incorporate AI have become versatile tools that can be
applied ubiquitously in various stages of drug development, such
as identification and validation of drug targets, designing of new
drugs, drug repurposing, improving the R&D efficiency, aggregat-
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 REVIEWS Drug Discovery Today  Volume 24, Number 3  March 2019

ing and analysing biomedicine information and refining the
decision-making process to recruit patients for clinical trials
[28–30]. These potential uses of AI provide the opportunity to
counter the inefficiencies and uncertainties that arise in the clas-
sical drug development methods while minimising bias and hu-
man intervention in the process [31].
The other uses of AI in drug development include the prediction
of feasible synthetic routes for drug-like molecules [32], pharma-
Reviews  INFORMATICS
that animal models exhibiting a disease-relevant phenotype with a
neural network classifier of >71% accuracy provided the most
predictive power [45]. The application of AI in the process of drug
development is proposed in Fig. 2. IBM Watson for Drug Discov-
ery, an AI platform, has identified five new RNA-binding proteins
(RBPs) linked to pathogenesis of a neurodegenerative disease
known as amyotrophic lateral sclerosis (ALS) [46].

cological properties [33], protein characteristics as well as efficacy
[34], drug combination and drug–target association [35] and drug
repurposing [36]. Also, the identification of new pathways and
targets using omics analysis becomes possible via the generation of
novel biomarkers and therapeutic targets, personalised medicine
based on omics markers and discovering the connections between
drugs and diseases [37,38].
DL has demonstrated outstanding success in proposing potent
drug candidates and accurately predicting their properties and the
possible toxicity risks [39]. Circumventing past problems in drug
development – such as analysis of large datasets, laborious screen-
ing of compounds while minimising standard error, requiring
large amounts of R&D cost and time of over US$2.5 billion and
a more than a decade [40] – are now possible using AI methods
[41]. With AI technology, new studies can be carried out in
assisting the identification of new drug targets, rational drug
designing and drug repurposing [42,43].
AI in understanding the pathway or finding molecular
targets
In drug development, AI has transformed the methods of pathway
or target identification to treat diseases. This was possible owing to
the incorporation of genomics information, biochemical attri-
butes and target tractability [44]. One study determined the plau-
sibility of predicting therapeutic targets using a computational
prediction application known as ‘Open Targets’ – a platform
consisting of gene–disease association data – and it was reported
AI in finding the hit or lead
The implementation of AI in the discovery of small drug-like
molecules concerns the utilisation of chemical space. Chemical
space provides the stage for identifying novel and high-quality
molecules because it is possible to computationally enumerate the
probable organic molecules [47]. Additionally, ML techniques and
predictive model software also contribute to the identification of
target-specific virtual molecules and association of the molecules
with their respective target while optimising the safety and effica-
cy attributes.
AI systems can reduce the attrition rates and the R&D expendi-
ture by decreasing the number of synthesised compounds that are
subsequently tested in either in vitro or in vivo systems [48]. A
variety of in silico techniques for profile selection such as virtual
ligand or structure-based design approaches can be used with the
available data on small-molecule modulator probes or their struc-
tural biology. DL becomes useful in instances where structural data
are insufficient. Thus, phenotypic data or disease, biology or
molecule network-based algorithms can be used. The validated
AI techniques can be used to increase the success rates in drug
development, whereas the AI techniques that are in development
must be validated before applying to the drug development pro-
cess. The most crucial part in the drug development process is the
synthesis of chosen molecules. Thus, AI is valuable owing to its
ability to prioritise molecules based on the ease of synthesis or
develop tools that are effective for the optimal synthetic route
[48,49].

Benchmark compounds set design

Predict target’s role in a disease
Al in drug Design of in silico compound libraries
development Identify novel targets
Predict druggability of targets
Predict signalling systems
Prediction of structure-activity Drug repurposing
relationship (SAR) Selection of patient population in Pharmacovigilance
Prediction of ADMET properties clinical trials to increase success rates

FDA approval,
Clinical candidate,
Validated Assay Lead molecule shown Drug, safe Drug,shows Drug,shows effect manufacture, Observation of
Outcomes shown effect in
target developed effect on target in humans effect in humans in large poplation post-marketing adverse effects
an animal model
survey

Phase ll Phase lll Phase lV

Drug development Target Biological Compound Hit/lead Lead Preclinical Phase I Approved drug
(proof of (multicentre (postmarketing
process validation assay screening identification optimisation development (1st in human) for clinical use
concept) trials) & surveillance)

Drug development Target-based drug discovery Opportunity for serendipitous identification of new therapeutic uses
strategies Phenotype-based discovery
Identification of new therapeutic uses

Drug development Approved drug

Phase l Phase ll Phase lll
process for clinical use

Drug development Drug repurposing

strategies
Al in drug
Interrogation of transcriptomic data
development

Drug Discovery Today

FIGURE 2
Utilisation of artificial intelligence (AI) in the drug development process. The outcomes and the strategies of the various components of the drug development
process are described. The applications of AI at each stage of drug development are also shown.

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Drug Discovery Today  Volume 24, Number 3  March 2019
AI in synthesis of drug-like compounds
Drug-like molecules are compounds that obey Lipinski’s rule of
five: (i) molecular weight <500 Da; (ii) H-bond donors <5; (iii) H-
bond acceptor <10; and (iv) calculated Log P (cLogP) <5. For the
synthesis of drug-like molecules, retrosynthesis is used extensively
by chemists. The first step in the retrosynthetic approach is to
analyse the target compounds recursively and to sequentially
convert them into smaller fragments or building blocks that can
be easily purchased or prepared. The second step is to identify the
reactions that will convert these fragments into target compounds.
The second step is the most challenging because it is difficult for
the human brain to interrogate the vast number of relevant
organic reactions available in the literature to pick the most
plausible reaction. AI would aid in predicting the best sought-after
reactions by filling the voids that cause high failure in expected
organic synthesis (commonly known as ‘out of scope’ com-
pounds). The voids in organic synthesis are mainly the result of
unpredictable steric and electronic effects and incomplete under-
standing of the reaction mechanism. Currently, several computer-
aided organic compound synthesis (CAOCS) systems are available
to assist chemists in selecting the synthesis route; however, it is not
a component of the computer-aided drug discovery (CADD) work-
flow.
Seglar et al. have developed a new AI platform named 3N-MCTS,
which combines three different deep neural networks with Monte
Carlo Tree Search (MCTS) for CAOCS. This platform can filter out
the most promising building blocks and select only well-known
reactions for the synthesis of target compounds. The platform, 3N-
MCTS, was proven to be much faster and better than that of
traditional computer-assisted retrosynthesis systems. The plat-
form was able to propose feasible synthesis routes without unrea-
sonable steps in a relatively short time. However, quantitative
prediction of enantiomeric or diastereomeric ratios and devising
natural product syntheses plans are an unmet need.
Predicting the mode-of-action of compounds using AI
The prospect of having an AI platform that can predict the on- and
off-target effects and in vivo safety profile of compounds before
they are synthesised excites those involved in the drug develop-
ment process – particularly medicinal chemists. The availability of
such platforms reduces the drug development time, R&D costs and
attrition rates. A few examples of such platforms are DeepTox
(predicts toxicity of new compounds) and PrOCTOR (predicts the
probability of toxicity in clinical trials) [51,52]. The predictive
accuracy of these platforms could be improved if a bigger and
refined dataset on toxicity and therapeutic profile of a varied set of
compounds is made available. However, this can only be achieved
if there is a willingness to share data among the industry.
Recently, an innovative AI tool, SPiDER, was developed [53] as
an alternative to chemoproteomics to advance natural products
for drug discovery. For proof-of-concept, SPiDER was used to
predict the molecular target of b-lapachone, a clinical-stage natu-
ral naphthoquinone with antitumour activity. The platform pre-
dicted b-lapachone as an allosteric and reversible modulator of 5-
lipoxygenase (5-LO). The prediction is validated using a 5-LO
functional assay. Another AI tool: read-across structure–activity
relationships (RASAR) [54], which links molecular structures and
toxic properties by mining a large database of chemicals, was
REVIEWS
reported to accurately predict the toxicity of unknown com-
pounds.
AI in selection of a population for clinical trials
An ideal AI tool to assist in clinical trials should recognise the
disease in patients, identify the gene targets and predict the effect
of the molecule designed as well as the on- and off-target effects. A
novel AI platform called AiCure was also developed as a mobile
Reviews  INFORMATICS
application to measure medication adherence in a Phase II trial of
subjects suffering from schizophrenia, where it was reported that
AiCure increased adherence 25% compared with the traditional
‘modified directly observed therapy’ [55]. Patient selection for a
clinical trial is a crucial process. Interrogating the relationship
between human-relevant biomarkers and in vitro phenotypes
affords a more predictable, quantifiable assessment of the uncer-
tainty of therapeutic responses in a specific patient. The develop-
ment of AI approaches to identify and predict human-relevant
biomarkers of disease allows the recruitment of a specific patient
population in Phase II and III clinical trials. The AI predictive
modelling in selection of a patient population would increase the
success rate in clinical trials [56,57].
AI in drug repurposing
With AI, the drug repurposing process becomes more attractive
and pragmatic. The concept of applying an existing therapeutic
to a new disease is advantageous because the new drug is
qualified go directly to Phase II trials for a different indication
without having to pass through Phase I clinical trials and
toxicology testing again [58,59]. In silico methods predicting
pharmacological properties of drug and drug repurposing using
transcriptomic data comprising various biological systems and
conditions through DL applications were reported. The meth-
ods described are based on high-level representations of data
utilising deep neural networks (DNNs), which is essentially a
highly adaptive multilayer system comprising connected and
interacting artificial neurons that perform various data trans-
formation [60]. In a study performed by Aliper et al., it was
demonstrated that DNNs could classify complex drug action
mechanisms on the pathway level, thus classifying drugs into
therapeutic categories according to their functional class, effi-
cacy, therapeutic use and toxicity [61]. Additionally, the
advances in precision medicine have resulted in the creation
of next-generation AI that offers the ability to design drug
molecules from the generative adversarial networks (GANs)
[62]. GANs are an astounding technology that uses DL to
produce photo-realistic pictures from text descriptions [63].
Thus, this platform can perform remarkable tasks beyond ana-
lysing data, such as imagining or creating new data modelled
on real data. Essentially, the GAN technique is an adversarial
game between two DNNs where, principally, one DNN evalu-
ates the output of the other iteratively and, in that adversarial
game, the two networks learn how to generate more perfect
molecules [62].
Another next-generation AI method used in in silico medicine is
reinforcement learning. The advantage of this AI technique is that
it is less dependent on learning from datasets, thus the networks
can recognise certain strategies in drug molecule design.
Zhavoronknov’s team designed algorithms that can reconstruct
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 REVIEWS
missing features from half-full datasets and interpret the differ-
ences in normal and diseased profiles within complex data [64].
One aspect of interest is the possibility of AI in designing drugs
with fewer side effects. The AI algorithm is also being trained to
differentiate between cardiotoxic and non-cardiotoxic drugs using
gene expression data from cells incubated with different drugs.
The team is currently competing their AI-designed molecules
against those designed by chemists. An attempt was made to
Reviews  INFORMATICS
capture innate knowledge that assists experienced medicinal che-
mists in identifying promising drug candidates by looking using
mobile electroencephalography to measure responses to the struc-
ture and numerical properties of a molecule. Apart from that, it
also searches for signs of bias in the types of drug molecules
preferred by chemists, which would not be apparent in AI-
designed molecule selection.
AI in polypharmacology
Currently, the ‘one-disease–multiple-targets’ paradigm domi-
nates over the ‘one-disease–one-target’ paradigm because of dee-
per understanding of pathological processes in diseases at the
molecular level. One-disease–multiple-targets is termed poly-
pharmacology [19]. Many databases, such as ZINC, PubChem,
Ligand Expo, KEGG, ChEMBL, DrugBank, STITCH, BindingDB,
Supertarget, PDB, among others, are available to integrate diverse
information of molecular pathways, crystal structures, binding
affinities, drug targets, disease relevance, chemical properties and
biological activities. AI could be used to probe these databases to
design polypharmacological agents. A success story of an AI
application in designing polypharmacological agents was recent-
ly published in the literature – the authors developed a compu-
tational platform, DeepDDI, for better understanding of drug–
drug interactions and associated mechanisms and prediction of
alternative drugs for intended clinical use without negative
health effects [65].
Partnerships between the pharma industry and AI
companies
With the rapid introduction of AI in healthcare, especially in the
years 2016 and 2017, numerous pharmaceutical companies have
made investments in and have joint ventures with AI companies
in the hopes of developing better healthcare tools. These include
the improvements in diagnostics or biomarkers and the identifi-
cation of drug targets and designing new drugs [66]. The transi-
tion from general medicine to modern AI healthcare focuses on
the basis of the data [67]. The analyses of these underlying data
coupled with ML or DL are subsequently formulated into algo-
rithms – thereby strongly contributing to progressive modern
healthcare that incorporates AI. Thus, numerous partnerships
between pharmaceutical industries and AI companies were re-
cently developed on a global scale. For instance, DeepMind
Technologies, a subsidiary of Google, collaborated with Royal
Free London NHS Foundation Trust to assist in the management
of acute kidney injury [68]. A global project that utilises data and
AI from NHS patients with rare diseases is UK’s 100 000 Genomes
Project; this project is in collaboration with Roche, Berg, Merck
and Biogen.
Atomwise is a pioneer in healthcare AI and is the first DL
technology for novel small molecule discovery. Known for its
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Drug Discovery Today  Volume 24, Number 3  March 2019
extraordinary speed, accuracy and diversity in structural chemis-
try using DL, Atomwise has assisted in the invention of new
potential medicines for 27 disease targets and is working with top
institutions such as Harvard University and Stanford University,
as well as pharmaceutical companies. Benevolent AI is one of the
AI tools currently used in drug development. It utilises the
strategy of text mining to analyse the available patents and other
genetics and biological information to extrapolate the relation-
ships between those entities to create highly informative graphs
consisting of dynamic maps with over one billion relationships.
The resulting graphs consisting of highly complex relationships
are believed to have the ability to provide information or identify
new links or knowledge gaps that can generate new hypotheses.
In contrast to human intervention where the element of bias is
present, AI adopts the disease-agonistic approach which permits
the unbiased views of scientific data that produce unbiased
hypotheses.
Exscientia is an AI company that specialises in phenotypic drug
discovery. Human analysis of extremely complicated datasets for
high-content phenotypic drug discovery is outperformed by AI by
a large margin [69]. The ease in rapidly evolving drug designs is
achievable through the testing of each newly designed compound
and then comparing it with its anticipated performance and other
molecules. Another notable AI start-up is Numerate. Numerate
focuses on ligand chemistry, ADMET and combinatorial ML with
classical approaches, giving emphasis on the transformation of
new medicine discovery by filling significant therapeutic gaps
through analysing large datasets pertaining to drug development
by applying algorithms.
A healthy spread of such partnerships covering various research
areas, such as the identification of novel small molecules [32], the
discovery of new treatment methods, monitoring the health data
via wearable technologies [70], among others, is concisely shown
in Fig. 3. These advances are forecasted to serve as contributing
factors to the betterment of healthcare services, improvement in
terms of efficiency in clinical trials, enhancement in stratified
medicine and more [71]. Presently, up to US$3 billion over the
course of 15 years will be spent to bring a new drug to market. This
trend is unsustainable and a change is inevitable because consu-
mers are not willing to pay more for medicines and for the cost of
the failures [72,73]. Thus, a change in the business model is
necessary, and AI offers such opportunity. These collaborations
demonstrate the importance of AI technology in allowing us to
explore a much bigger design space and discover rare molecules
that have properties, which is beyond the conventional finds if we
relied solely on traditional HTS.
Concluding remarks
Currently, there are no developed drugs that have utilised AI
approaches but, based on the advances described in this review,
it is likely that it will take a further 2–3 years for a drug to be
developed. Interestingly, experts strongly believe that AI will
permanently change the pharmaceutical industry and the way
drugs are discovered. However, for an individual to be efficient in
drug development using AI, the individual should know how to
train algorithms, requiring domain expertise. This creates the
suitable workspace whereby AI and medicinal chemists can work
closely together, because the former will be able to help in analys-
Drug Discovery Today  Volume 24, Number 3  March 2019 REVIEWS

Al Pharma Al

Confidential

Drug repurposing To announce the mechanisms

of Al-based patient monitoring
platform can improve adherence

To track real-time data via smartphones To predict how cancer types

and other wearable technologies will respond to treatment

Reviews  INFORMATICS
To target prsonalised medicine
using machine learning and
large-scale genome sequencing

To identify new treatments

for psychiatric diseases

To discover novel and

selective small molecules To discover new treatment
To create bispecific small molecules options and to improve
for immuno-oncolog therapies chronic disease management

To identify novel biological To accelerate drug discovery

targets and pathway in immuno-oncology

To license the rights to develop, To identify new drug targets,

manufacture and commercialise combination therapies and
clinical stage drug candidates patient selection strategies
in immuno-oncology
To find new drug candidates for glaucoma
To improve health outcomes
To accelerate clinical development for breast cancer patients
of new therapies for breast cancer
To design small molecule modulators
of ryanodine receptor 2
To find and validate potential
cancer drug targets To identify candidates for oncology,
gastroenterology and CNS disorder
To evaluate novel targets for for clinical trials
neurodegenerative disorders such
as parkinson’s disease To generate novel small molecule
drug leads from an unnamed
To assess potential biomarkers for
cardiovascular disease target
seasonal flu vaccine performance
To announce the mechanisms of
Al-based patient monitoring Confidential
platform can imrove adherence
To optimise clinical trial
planning with AI

Drug Discovery Today

FIGURE 3
Partnerships between artificial intelligence (AI) and pharmaceutical companies and areas of collaboration in drug development.

ing huge datasets and the latter can train machines, set algorithms Conflicts of interest
or optimise the analysed data for a speedier and accurate drug There are no funding sources to declare for the writing of this
development process. Despite the benefit of AI in speeding up drug manuscript. Both authors contributed to the drafting, analysis,
development, real experiments still need to be conducted. Addi- editing and submission of the manuscript.
tionally, AI can be used in assisting gene therapy or other therapies
that are currently not available to us as tools in healthcare. With Acknowledgements
AI, the possibility of combining regenerative medicine with phar- The authors thank the International Medical University for the
macology and gene therapy emerges. library facilities.

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