Principal Scientist, Biochemistry & Biophysics

C4 Therapeutics, Inc.; Watertown (MA); On-site; USD 185,000 - 204,000; Full time

Job summary

C4 Therapeutics, Inc. in Massachusetts is seeking an experienced scientist to lead the Biochemistry and Biophysics group within Lead Discovery. The role blends hands-on lab work with matrixed management to drive hit validation, SAR, and mechanism-of-action understanding for targeted protein degradation programs.

The successful candidate will design and optimize biochemical and biophysical assays, manage CROs, and mentor scientists while translating data into actionable drug discovery decisions.

Qualifications

• PhD with 8+ years post-graduate biotech/pharma discovery experience.
• Expertise in quantitative characterization of protein–protein and protein–small molecule interactions.
• Ability to lead complex scientific operations across multidisciplinary teams under aggressive timelines.
• Experience contributing to early-stage drug discovery and guiding SAR, compound prioritization, and program decisions.
• Excellent communication, accountability, and organizational skills for diverse audiences.

Responsibilities

• Provide scientific and operational leadership for biochemical and biophysical assay strategies supporting hit validation, hit-to-lead, lead optimization, and mechanistic characterization of degraders.
• Design, develop, optimize, and oversee assays to characterize protein–protein and protein–small molecule interactions and ternary complexes.
• Apply expertise in SPR, BLI, TR-FRET, AlphaLISA, and fluorescence polarization to generate high-quality data.
• Lead complex operational workstreams across multidisciplinary teams with clear goals, timelines, and data quality expectations.
• Integrate data across assays to inform risk, next experiments, and compound prioritization.

Skills

Biochemistry

Biophysics

Assay design

Data analysis

Project leadership

Communication

Drug discovery

SAR guidance

Education

PhD in Biochemistry, Biophysics, Chemical Biology, or Enzymology

Tools

SPR

BLI

TR-FRET

AlphaLISA

Fluorescence polarization

Job description

About C4 Therapeutics

C4 Therapeutics (C4T) (Nasdaq: CCCC) is a clinical-stage biopharmaceutical company dedicated to delivering on the promise of targeted protein degradation science to create a new generation of medicines that transforms patients’ lives. C4T is progressing targeted oncology programs through clinical studies and leveraging its TORPEDO® platform to efficiently design and optimize small-molecule medicines to address difficult-to-treat diseases. C4T’s degrader medicines are designed to harness the body’s natural protein recycling system to rapidly degrade disease-causing proteins, offering the potential to overcome drug resistance, drug undruggable targets and improve patient outcomes. For more information, please visit www.c4therapeutics.com .

About C4 Therapeutics

C4 Therapeutics (C4T) (Nasdaq: CCCC) is a clinical-stage biopharmaceutical company dedicated to delivering on the promise of targeted protein degradation science to create a new generation of medicines that transforms patients’ lives. C4T is progressing targeted oncology programs through clinical studies and leveraging its TORPEDO® platform to efficiently design and optimize small-molecule medicines to address difficult-to-treat diseases. C4T’s degrader medicines are designed to harness the body’s natural protein recycling system to rapidly degrade disease-causing proteins, offering the potential to overcome drug resistance, drug undruggable targets and improve patient outcomes. For more information, please visit www.c4therapeutics.com .

Job Summary

The Lead Discovery group at C4T is looking for an enthusiastic, creative, and experienced scientist to lead the biochemistry and biophysics team. In this role, you will serve as a scientific leader who combines deep technical expertise in protein–protein interactions, protein–small molecule interactions, and general biochemical and biophysical assay approaches with the operational experience to manage complex workstreams across multidisciplinary discovery teams. You will play a central role in advancing early discovery programs by designing and integrating biochemical and biophysical strategies that enable hit validation from screening efforts, SAR development, mechanism-of-action understanding, and progression of targeted protein degradation programs. This is a role that gives you the opportunity to both work in the lab as an individual contributor as well as take on direct and matrixed management responsibilities. You will operate at the interface of Lead Discovery, Biology, Medicinal Chemistry, Computational Chemistry, Structural Biology, using experience and proficiency in project and CRO management, bringing clarity, accountability, and scientific rigor to tackle complex program and platform needs.

Your Role

• Provide scientific and operational leadership for biochemical and biophysical assay strategies that support efforts in 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 deep expertise in biochemical and biophysical methods such as SPR, BLI, TR-FRET, AlphaLISA, fluorescence polarization and related approaches 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 key 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, helping to translate biochemical and biophysical insights into actionable drug discovery decisions.
• Manage CRO relationships and external collaborations as needed, 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 across the organization through technical guidance, cross-functional collaboration, and leadership by example, without requiring formal people management responsibilities.
• Contribute to the evolution of C4T’s Lead Discovery capabilities, including the identification and implementation of new technologies, workflows, and platform improvements that strengthen targeted protein degradation discovery.

Your Background

Required

• A PhD in biochemistry, biophysics, chemical biology, enzymology, or a closely related discipline, with 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, with the 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.

Preferred

• 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.

Compensation

The base pay range for this position at commencement of employment is expected to be between $184,851.00 and $204,309.00 annually; however, base pay offered may vary depending on multiple individualized factors, including job-related knowledge, skills, and experience.

C4 Therapeutics is an Equal Opportunity Employer.