Drug Discovery Case Studies I Integrated Drug Discovery

Case Studies of Pharmaron’s Integrated Drug Discovery and Development Teams

Discover how Pharmaron teams work side‑by‑side with clients to turn ideas into therapies. These drug discovery case studies highlight how our scientific expertise and creativity have helped discover and advance promising drug candidates.

Drug Discovery Case Studies: From Challenge to Decision-Making Confidence

Explore how specific scientific questions were addressed across programs. Each case study highlights the approaches used, the data generated, and how these insights supported progression decisions. Expand to see how similar challenges have been tackled in practice.

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Selective PARP1 Inhibitor Discovered in 12 Months with Strong Translational and Developability Profile

Scope: Design and deliver a selective PARP1 inhibitor with strong target engagement and in vivo efficacy, while proactively addressing developability risks.

Phases supported: Hit-to-lead > Lead optimization > Developability assessment
Target: DNA repair enzyme | Pathway: DNA damage response | Indication: Cancer
Modality: Small molecule

As part of this drug discovery case study we determined the developability of the newly discovered drug NB-0290

The novel PARP1 inhibitor NB-0290 was discovered in collaboration with the China-based biotech New Bay Pharma. In just 12 months, the lead compound was identified and optimized through cross‑disciplinary integration spanning medicinal chemistry, biophysics, in vitro and in vivo biology, DMPK, and human PK modeling. The candidate demonstrated selective PARP1 binding, slow off‑rate kinetics, cellular potency, tumor regression in xenografts, and a predicted low human daily dose. Developability assessment positioned NB-0290 for preclinical development.

Read the full drug discovery case study here

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First‑in‑Class GCN2 Activator Advances from Discovery to Phase 1

Scope: Discover and develop a first-in-class small molecule activator of GCN2 kinase to induce a stress-response state in tumor cells that limits their ability to grow.

Phases supported: Hit-to-lead to Lead optimization to Preclinical candidate nomination to IND
Target: Kinase | Pathway: Integrated stress response | Indication: Cancer
Modality: Small molecule

3D ball-and-stick molecular model of the drug HC-7366, with color-coded carbon, nitrogen, oxygen, sulfur, fluorine and chlorine atoms

Pharmaron collaborated with a US-based biotech in this project. We provided medicinal chemistry, CADD, in vitro biology, in vivo efficacy, and DMPK expertise to successfully discover and evaluate the drug HC-7366 as well as performed a comprehensive evaluation of its mechanism of action. The compound is currently in clinical Phases 1a and 1b (as of January 2026).

Read the case study of discovering HC-7366 here

Access the description of the compound’s mechanism of action here

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Discovery of Selective Macrocyclic PKCθ Inhibitors

Scope: Discover and optimize selective and orally available PKCθ inhibitors to modulate T‑cell driven diseases to target psoriasis and atopic dermatitis.

Phases supported: Hit-to-lead to Lead optimization
Target: Kinase | Pathway: Immune cell signaling | Indication: Inflammatory skin diseases
Modality: Small molecule

Orange stick model of a macrocyclic PKCθ inhibitor bound in a protein active site, with yellow dashed hydrogen bonds to surrounding residues

Challenge: In the past, selective PKCθ inhibition has remained elusive due to a trade-off between isoform selectivity (especially over PKCα), potency, and acceptable safety profiles, limiting clinical translation.

Approach: In collaboration with a Europe-based biotech, Pharmaron applied an integrated drug discovery strategy combining medicinal chemistry, CADD, crystallography, in vitro biology, and ADME to explore macrocyclic scaffolds to address the selectivity challenge.

The identified inhibitors showed:

Enhanced isoform selectivity for reduced PKCα-related safety risks
High target potency through conformationally optimized binding
Balanced ADME and PK properties
Expansion into differentiated chemical space, overcoming limitations of prior scaffolds

Iterative design and structural insights led to multiple optimized series with strong selectivity, functional activity in immune assays, and profiles suitable for advanced evaluation.

Learn more about Pharmaron’s macrocycles case study:

Learn more about Pharmaron’s macrocycles case study in our webinar here

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Targeting DNA Damage Response: Discovery of a Potent Dual ATM/DNA‑PK Inhibitor

Scope: Design and develop a dual inhibitor targeting ATM and DNA‑PK to block complementary DNA double‑strand break repair pathways, with the goal of intensifying DNA‑damage responses and enhance sensitivity to radiation and combination therapies.

Phases supported: Hit ID to IND Filing
Target: Kinases | Pathway: DNA damage response | Indication: Cancer
Modality: Small molecule

Translucent space-filling surface over a stick model of XRD-0394, a potent dual ATM/DNA-PK inhibitor, with color-coded heteroatoms

This project was sponsored by a US-based biotech and an academic institution. Pharmaron provided medicinal chemistry, CADD, in vitro biology and DMPK expertise to successfully discover and evaluate XRD-0394, an orally administered dual ATM/DNA‑PK inhibitor that disables both major DNA repair pathways, enhancing radiation‑induced tumor cell killing and potentiating PARP and topoisomerase I inhibitors. The compound has successfully completed clinical Phase 1a (as of January 2026).

Read the full case study here

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Overcoming Poor Palatability: In Vivo Efficacy Model Enables Optimization of Bitter‑Blocking Compounds

Scope: Optimize novel P2X2/P2X3 antagonists capable of blocking bitter taste signaling in vivo.

Phases supported: Hit-to-lead
Target: Ion channel | Pathway: Sensory signaling | Indication: Taste modulation
Modality: Small molecule

This schema shows our case study setup for tasting bitterness in water by mice

Scientists at the Monell Chemical Senses Center identified P2X2/P2X3 taste‑nerve signaling as a universal mechanism underlying the bitterness of many medicines. Pharmaron optimized a translational in vivo mouse lick model based at Monell, enabling PK‑PD‑driven screening, potency‑guided predictions, and optimization of bitter‑blocking candidates. This integrated effort delivered novel small molecules with strong in vivo suppression of bitter‑taste responses, supporting the development of more palatable oral medicines.

Read the full lead optimization case study here

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Targeting both domains of DNA Polymerase Theta

Scope: Identification and optimization of novel compounds targeting either the helicase domain or the polymerase domain of DNA polymerase theta.

Phases supported: Hit-to-lead to PCC
Target: DNA polymerase theta | Pathway: DNA damage response | Indication: Oncology
Modality: Small molecule and macrocyclic small molecule

IDD case study on dna damage response pathway against dna polymerase theta

Approach: In collaboration with NewBay Pharma, a China-based biotech, we pursued a dual strategy, targeting both the polymerase and helicase domains in parallel to compare them directly and maximize the chances of identifying a candidate. An integrated approach combining medicinal chemistry, structural design, in vitro and in vivo biology, and DMPK was used to explore macrocyclic scaffolds and enable allosteric inhibition, conformational control, and access to differentiated chemical space.

Project outcome:

Our strategy delivered potent, novel inhibitors for both helicase and polymerase domains, with the helicase inhibitor showing stronger DNA damage induction and superior cellular potency
Robust in vivo efficacy, with tumor regression in BRCA-deficient xenograft models in combination with PARP inhibition
Favorable ADME/PK profile, supporting sustained exposure and in vivo activity
Clean safety profile with no adverse findings in rat tox and dog DRF studies
PCC nomination for the helicase inhibitor

Download our poster to view the case study

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Two Pharmaron scientists walking through a laboratory corridor while discussing integrated drug discovery services.

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