Insilico Medicine's Abu Dhabi research team has discovered two lead compounds targeting blood cancers using generative artificial intelligence, demonstrating that drug discovery capabilities are expanding beyond traditional pharma hubs. The compounds, called ISM-PR25 and ISM-PR44, achieved exceptional potency against Bruton's tyrosine kinase (BTK), a protein that fuels chronic lymphocytic leukemia and mantle cell lymphoma. The research was published in the Journal of Medicinal Chemistry on August 14, 2026, and represents a significant step in building drug discovery infrastructure in the Middle East.

Why Does This Blood Cancer Discovery Matter?

Blood cancers like chronic lymphocytic leukemia and mantle cell lymphoma affect B cells, a type of immune cell critical to the body's defense system. BTK is an established therapeutic target because it supports the signaling that allows these cancer cells to grow and survive. While BTK inhibitors have improved treatment options, cancer cells can develop resistance mutations that render existing drugs ineffective.

Insilico's approach uses a different strategy called proteolysis-targeting chimeras, or PROTACs. Rather than simply blocking BTK, PROTACs recruit the cell's own protein degradation machinery to remove BTK entirely. This mechanism offers a potential advantage: it may overcome resistance mutations that plague traditional inhibitors. However, developing selective, orally bioavailable PROTACs has proven challenging for the industry.

How Did AI Accelerate This Discovery?

Insilico's team used its proprietary generative AI platform, called Chemistry42, to design two novel cereblon-binding warheads, labeled ISM-WH1 and ISM-WH2. Cereblon is a protein that helps recruit the machinery needed for protein degradation. After designing these warheads, researchers optimized the molecular linkers connecting them and evaluated more than 40 compounds, carefully balancing BTK degradation activity, selectivity, cellular toxicity, and pharmacokinetic properties.

The lead compounds achieved remarkable potency. ISM-PR25 and ISM-PR44 both achieved BTK degradation DC50 values of 0.04 and 0.05 nanomolar in malignant B cells, respectively. A DC50 is the concentration required to degrade 50 percent of the target protein. Both compounds showed activity against wild-type BTK and mutated forms, with no unintended degradation of off-target proteins like IKZF1, IKZF3, and GSPT1.

"In this study, we present highly potent BTK-targeting PROTACs with favorable pharmacokinetic and toxicity profiles, alongside novel selective CRBN-targeting warheads," stated Dr. Alexey B. Mantsyzov, corresponding author of the study. "Leveraging these novel warheads combined with extensive linker optimization enabled the discovery of promising lead candidates."

Dr. Alexey B. Mantsyzov, Corresponding Author, Insilico Medicine

In preclinical testing, oral bioavailability in mice reached 26 percent for ISM-PR25 and 29 percent for ISM-PR44. Both compounds reduced BTK levels in circulating mouse B cells following a single oral dose of 3 milligrams per kilogram, supporting further investigation as potential oral therapies.

What Does This Mean for the UAE's Drug Discovery Ambitions?

This BTK discovery builds on Insilico's earlier announcements in drug discovery from the UAE. In April 2026, the company announced ISM0387, an MTA-cooperative PRMT5 inhibitor, which was the first drug ever discovered in the UAE and nominated as a preclinical candidate. In July 2026, Insilico announced ISM9528, a potential first-in-class, non-opioid candidate for chronic pain and its 31st preclinical candidate since 2021.

"Our ambition in Abu Dhabi is to build a team that can originate new medicines and contribute to international drug discovery," said Alex Aliper, PhD, President of Insilico Medicine. "Following our UAE-based discovery of the PRMT5 preclinical candidate, this BTK degrader publication demonstrates the range of scientific problems our local team can tackle. It is another step in building lasting drug discovery capabilities here in the UAE."

Alex Aliper, PhD, President of Insilico Medicine

Insilico Medicine's UAE operations were established with support from the Abu Dhabi Investment Office, following a partnership announced in 2023. The company operates from the IRENA headquarters in Masdar City and has developed research relationships with MBZUAI, Khalifa University, and NYU Abu Dhabi. In 2026, Insilico further strengthened its local presence through a strategic partnership with the Emirates Drug Establishment to support pharmaceutical innovation in the UAE.

Steps to Understanding AI's Role in Modern Drug Discovery

• Generative AI Design: AI platforms like Chemistry42 generate novel molecular structures by learning patterns from existing compounds, then propose new candidates that meet specific criteria like potency and selectivity.
• Linker Optimization: After AI designs the core warheads, researchers systematically test different molecular linkers connecting them, evaluating dozens of variations to balance efficacy and safety properties.
• Preclinical Validation: Lead compounds undergo laboratory and animal testing to confirm potency, measure oral bioavailability, assess off-target effects, and establish safety profiles before human trials.

Insilico Medicine's broader performance underscores the commercial momentum behind AI-driven drug discovery. The company reported total revenue of approximately 106 million dollars in the first half of 2026, a 287 percent year-over-year increase, and achieved its first profitable half-year since listing, with an adjusted net profit exceeding 51 million dollars. This milestone was driven by out-licensing, co-development, and research and development collaborations with global partners including Eli Lilly, Servier, Takeda, SK Biopharmaceuticals, Qilu Pharmaceutical, Hygtia Therapeutics, CMS, and Tenacia.

As of late August 2026, Insilico nominated nine development candidates within nine months, setting a new company record for annual pipeline productivity and achieving eight clinical milestones across its proprietary and co-developed programs. Leading this progress is rentosertib, the world's first drug candidate discovered and developed using generative AI, which has advanced to a Phase III trial evaluating its potential for idiopathic pulmonary fibrosis.

The BTK degrader compounds remain research-stage lead candidates. Further preclinical and clinical studies would be needed to establish their potential as medicines. However, the discovery demonstrates that AI-powered drug discovery is no longer confined to Silicon Valley or traditional pharma centers; it is taking root in emerging innovation hubs like the UAE, where regional investment and academic partnerships are creating new pathways for bringing treatments to patients worldwide.