D. E. Shaw Research conducts drug discovery programs both independently and in collaboration with other biopharmaceutical companies and research laboratories. All of our computational work is performed in‑house using a combination of our special‑purpose Anton supercomputers and high‑speed commodity hardware. We do not maintain in‑house “wet lab” facilities, but routinely design experiments for execution under our direction by various specialized contract research organizations (CROs).
Our drug discovery activities fall into three categories, each of which is enabled in part by the use of Anton‑based MD simulations, machine learning methods, and other advanced computational technologies:
Elucidating the molecular mechanisms of pathological biological processes
Identifying previously undiscovered biomolecular phenomena that may be
relevant to the pathogenesis of potentially treatable human diseases
Determining how the binding of a given molecule at a given binding site
modulates the function of a protein implicated in a given disease
Exploring at an atomic level of detail the effects of inherited or acquired
mutations that are known to be associated with certain pathologies
Identifying new molecular strategies for pharmaceutical intervention
Discovering potentially druggable three‑dimensional protein configurations that have been inaccessible to experimental structure determination
Finding new, previously untargeted binding sites, including cryptic or
ephemeral binding pockets and novel sites for allosteric modulation
Identifying ligand features that tend to stabilize or destabilize particular
protein structures, or to promote or preclude particular interactions
Using a combination of computational and experimental techniques to generate or screen small‑molecule compounds
Designing highly selective compounds that bind strongly to the target protein while avoiding toxicity‑inducing interactions with related proteins
Predicting and optimizing biopharmaceutical properties such as solubility and
membrane permeability
Our research, technologies, and pharmaceutical expertise have each played an important role in bringing seven drugs into clinical trials. We designed three of these drugs independently; the other four were discovered under a multi‑target collaboration and licensing agreement with Relay Therapeutics (NASDAQ: RLAY), a separate company of which D. E. Shaw Research was a co‑founder. These clinical-stage drugs include:
Drugs we developed independently
DES‑9384, which inhibits TRPA1, a protein involved in such conditions as diabetic peripheral neuropathic pain, chronic lower back pain, and chronic cough
DES‑7987, which inhibits KCa3.1, a protein implicated in asthma, ischemic stroke, and lung fibrosis, among other diseases
Drugs we collaborated on with Relay Therapeutics
RLY‑4008, which targets the receptor tyrosine kinase FGFR2, and which was licensed by Relay to Elevar Therapeutics in 2024 as a potential therapy for cholangiocarcinoma and other solid tumors
RLY‑2608, which is designed to be the first allosteric, pan‑mutant (H1047X, E542X and E545X) and isoform‑selective PI3Kα inhibitor, and which is being studied as a potential treatment for breast cancer, solid tumors, and vascular malformations
D. E. Shaw Research welcomes the opportunity to collaborate with other pharmaceutical and biotech companies on the discovery and development of novel therapeutics.