Senior Scientist I/II, In Vitro Pharmacology

Are you ready to turn novel, in vivo-validated targets into small molecule drug programs — building the assays, screening cascades and human-relevant models that decide which chemistry moves forward?

Gordian is the leader in applying in vivo screening for target discovery. Our screens are producing novel targets faster than traditional discovery can, but those targets only become medicines if we can drug them, and in vitro pharmacology is where that starts. As our Senior Scientist, In Vitro Pharmacology, you will build assays for targets no one has drugged before, own the screening cascades our medicinal chemists design against, and set the standard for in vitro data at Gordian.

Journey + Destination:

Gordian Biotechnology is a therapeutics company designed as a machine that systematically

reveals the right way to cure age-related diseases: a machine for creating time.

To do that, we built Mosaic Screening, which makes causal validation both grounded in human

pathophysiology and radically more scalable in living diseased tissue. It lets us measure the causal effects of hundreds of perturbations directly in vivo, which reveals therapeutic maxima across vast target spaces (more details on our website and in our preprint). The machine is already producing wins: across six disease areas, we have mapped nearly as many targets as the field reported in 20 years, advanced a novel osteoarthritis candidate into IND-enabling studies, and started an obesity drug-discovery collaboration with Pfizer.

But there are still many diseases left to cure, and expanding the machine to tackle them starts with its most important resource: its people and culture. We work as a team, using clear goals, open communication, and direct feedback to make autonomous decisions with the bigger picture in mind. We aim for extraordinary outcomes, continually improving how we work and acting on what will create the most progress, even in unknown territory. We have deliberately designed an environment to sustain that standard: few standing meetings, hands-on experimentation and pre-mortems, weekly team lunches, and unlimited vacation that people are encouraged to use. You can dive deeper into our culture here.

This way of working has been crucial to Gordian’s success. In this role, you will help turn the targets the machine produces into small molecule medicines.

The Role:

Your mission is to make three things work across our obesity, kidney (CKD/DKD) and heart failure (HFpEF) programs:

1. Assays for novel targets. Most of our targets have no tool compounds, no off-the-shelf assay and incomplete pathway biology. You will design, develop and validate the biochemical, biophysical and cell-based assays that let us find and optimize chemical matter against them.
2. The screening cascade. Through working with our medicinal chemists, you will design the cascade from hit identification through lead optimization — primary, orthogonal, counter-screen, selectivity, functional and mechanism of action — set progression criteria and keep data flowing on a 1-2 week cadence that drives design-make-test cycles.
3. Mechanism in human systems. Through working with our ex vivo team, you will support to identify and develop disease-relevant human models, define target engagement, mechanism of action and efficacy readouts, and benchmark against standard-of-care drugs where it matters.

You will direct external work as well as your own: scoping, selecting and managing CROs for screening, transferring assays with bridging studies, and making sure every external number meets the same standard as ours. You will bring a recommendation, not just data, to target and program reviews: is the target tractable, is the chemistry real and selective, and should a program advance, pause or stop? And you will build Gordian’s in vitro pharmacology capability, setting up the equipment, assays and SOPs that a growing small molecule portfolio needs.

Understanding assays deeply is the heart of this role. Running an assay kit is not enough. You will know how each signal is generated and how it fails, why an IC50 moves when conditions change, and how to tell real pharmacology from a compound artifact. When an assay drifts, a reference compound shifts, or in-house and CRO data disagree, you find the root cause by isolating variables, not by re-running until it works. Every number that leaves your bench or our CROs is one Chemistry can design against.

One thing to be clear about: this is a bench role that also directs external work. Roughly half of your time is hands-on assay development and execution in our lab, especially new-target assays and disease-relevant human cell models. The rest is cascade design, CRO management, data analysis and communication. We are not looking for someone who only runs assays others designed, or who designs a cascade from a desk and learns what happened from CRO data files. The bench time is how you earn the credibility to set the standard for in vitro data at Gordian.

In your first month, learn Gordian’s platform well enough to explain it unaided to an external partner; get up to speed on the target validation packages and status of our obesity, CKD/DKD and HFpEF programs and our active small molecule work; audit our existing in vitro assays and CRO data; and write an assay plan for your first novel target with our Chemistry and Biology leads.

By two months, you will have personally developed and validated the first novel-target assay in our lab, with a validation report and an SOP another scientist can follow. Your first CRO study will be launched, with you owning vendor selection, scope and data acceptance criteria, and you will have agreed with our ex vivo team and disease lead on the human system, readouts and proof-of-mechanism criteria for your first target.

By three months, the screening cascade for your first program, including progression criteria, will be agreed with Chemistry and Biology, your first SAR data set will be in Chemistry’s hands, and the plan for counter-screens and orthogonal assays will be set.

By six months, you will have two or more validated primary assays for novel targets, a full cascade running for at least one program with a steady 1-2 week turnaround, disease-relevant human systems on track, and assay issues caught before they reach an SAR decision. Over time, you will build the in vitro data packages that carry Gordian’s targets to lead optimization and development candidates.

And You:

You have a track record of success in high-agency work, consistently creating momentum rather than waiting for direction.

You want to do your best work alongside exceptional teammates and are energized by environments where people push each other to think more clearly, work at a higher standard, and grow into better versions of themselves.

You truly want to play a key role in an early-stage startup validating new targets for intractable diseases of aging: a fast-paced environment full of both uncertainty and new challenges, demanding relentless resourcefulness.

You understand in vitro pharmacology from first principles. You can explain affinity versus potency versus efficacy, why an EC50 or IC50 shifts with substrate or agonist concentration, receptor reserve or cell background, and how competitive, allosteric, tight-binding and time-dependent mechanisms show up in your data. You read curve shapes correctly and can bridge biochemical, cellular and tissue potency.

You know how assays work, and how they fail. You understand how common formats generate signal — TR-FRET/HTRF, AlphaLISA, luminescence, fluorescence polarization, SPR, radioligand binding, reporter and high-content imaging — validate to statistical standards (Z′, MSR), and recognize compound artifacts such as aggregation, interference and cytotoxicity. You have fixed a drifting assay or an in-house versus CRO mismatch and can walk through exactly how.

You have built small molecule programs. You have a Ph.D. in pharmacology, biochemistry, cell biology, physiology or a related field and 5+ years in industry small molecule drug discovery (an M.S. with 10+ years of directly relevant industry experience will also be considered). You have designed or owned a screening cascade from hit identification through lead optimization or candidate nomination, partnering with medicinal chemists on SAR, and your experience includes cardiometabolic, renal or cardiovascular drug discovery.

You build assays for targets no one has drugged before. You have developed assays from scratch for poorly characterized targets with no tool compounds or established readouts, across target classes such as GPCRs, enzymes, nuclear receptors and transporters.

You have scoped and managed CRO studies, transferred assays with bridging data, and caught and corrected external data-quality problems. You analyze data rigorously (e.g., GraphPad, Genedata, Spotfire; Python or R a plus) and document your work so others can find, reproduce and build on it.

You communicate so that decisions follow. You can explain what an assay measures, and what it does not, to chemists, biologists and executives, and you bring a clear recommendation rather than a data dump.

Additional valuable skills if you have them

• Experience across more than one of kidney, cardiac and metabolic biology.
• Target engagement and biophysical methods such as CETSA, NanoBRET or SPR.
• First-in-class target experience, with no prior chemistry or tool compounds.
• Lab automation, liquid handling or high-content imaging.
• Advanced human cell models: iPSC-derived cells, 3D cultures or organoids, engineered heart tissue, kidney organoids or microphysiological systems.
• Understanding of PK/PD and in vitro to in vivo translation in cardio-renal disease.
• Partner- or BD-facing experience presenting preclinical data.

The Details: 

This is an onsite role in South San Francisco because hands-on lab work is central to it. Gordian offers meaningful equity, a competitive salary, full health, dental, vision, and life insurance, a 401(k) with match, onsite lunch three days a week, an onsite gym, an unlimited vacation policy, and access to world-class mentors and advisors.