Principal Scientist, Biochemistry & Biophysics

C4 Therapeutics•Watertown, MA

About The Position

C4 Therapeutics (C4T) is a clinical-stage biopharmaceutical company focused on developing new medicines through targeted protein degradation science. The company utilizes its TORPEDO® platform to create small-molecule medicines for difficult-to-treat diseases, particularly in oncology. C4T's degrader medicines aim to use the body's natural protein recycling system to degrade disease-causing proteins, potentially overcoming drug resistance and improving patient outcomes. The Lead Discovery group is seeking a scientist to lead the biochemistry and biophysics team, combining technical expertise with operational experience to manage complex workstreams within multidisciplinary discovery teams. This role is crucial for advancing early discovery programs by designing and integrating biochemical and biophysical strategies for hit validation, SAR development, mechanism-of-action understanding, and progression of targeted protein degradation programs. The position offers opportunities for both individual contribution in the lab and management responsibilities. The scientist will work at the intersection of Lead Discovery, Biology, Medicinal Chemistry, Computational Chemistry, and Structural Biology, managing projects and CROs to address program and platform needs.

Requirements

PhD in biochemistry, biophysics, chemical biology, enzymology, or a closely related discipline.
At least eight years of post-graduate experience, including significant experience in a biotechnology or pharmaceutical drug discovery setting.
Demonstrated expertise in quantitative characterization of protein–protein and protein–small molecule interactions, including assay design, data analysis, troubleshooting, interpretation, and strategic application of biochemical and biophysical methods for small-molecule discovery.
Proven ability to lead complex scientific operations across multidisciplinary teams, including prioritizing workstreams, coordinating stakeholders, managing dependencies, and delivering high-quality outputs under aggressive timelines.
Experience contributing to early-stage drug discovery programs and using biochemical or biophysical data to guide SAR, compound prioritization, and program decision-making.
Excellent communication, accountability, and organizational skills.
Ability to explain complex technical information, data limitations, and recommended next steps to both scientific and non-specialist audiences in a fast-paced, collaborative environment.

Nice To Haves

Experience in targeted protein degradation, including characterization of heterobifunctional degraders, molecular glues, E3 ligase biology, ternary complex formation, cooperativity, and degradation-relevant mechanisms.
Familiarity with structural biology, computational chemistry, DEL screening, proteomics, or cell pharmacology workflows and how these inputs integrate with Lead Discovery decisions.
Experience with management activities for full-time employees, including coordinating workloads, coaching and mentorship, and performance management activities.

Responsibilities

Provide scientific and operational leadership for biochemical and biophysical assay strategies supporting hit validation, hit-to-lead, lead optimization, and mechanistic characterization of molecular glue degraders and heterobivalent degraders.
Design, develop, optimize, and oversee assays to characterize protein–protein interactions, protein–small molecule interactions, and ternary complexes, including binding kinetics and functional activity.
Apply expertise in biochemical and biophysical methods such as SPR, BLI, TR-FRET, AlphaLISA, and fluorescence polarization to generate high-quality data.
Lead complex operational workstreams across multidisciplinary teams, ensuring alignment on goals, priorities, timelines, experimental plans, data quality expectations, and decision points.
Integrate data across assay formats and functional disciplines to provide clear interpretation, identify risks and limitations, recommend next experiments, and influence compound prioritization and program strategy.
Serve as a senior scientific thought partner to project teams and functional leaders, translating biochemical and biophysical insights into actionable drug discovery decisions.
Manage CRO relationships and external collaborations, including assay transfer, protocol development, troubleshooting, data review, timelines, budgets, and performance expectations.
Drive rigorous experimental design, assay validation, data reproducibility, and transparent communication of results, limitations, and recommendations.
Mentor and influence scientists through technical guidance, cross-functional collaboration, and leadership by example.
Contribute to the evolution of C4T’s Lead Discovery capabilities, including identifying and implementing new technologies, workflows, and platform improvements.