Scientist, Medicinal Chemistry

tl;dr General Proximity is a seed-stage startup developing the next generation of induced proximity medicines (IPMs). Our OmniTAC drug discovery engine furnishes molecules that co-opt existing cellular machinery to overcome therapeutic challenges, which have remained unapproachable to other modalities for decades.

We are seeking a first-rate medicinal chemist to help us pioneer this uncharted frontier of drug discovery.

Our Story A long-standing challenge in drug discovery is the development of molecules capable of modulating difficult or "undruggable" targets. Disease-causing proteins can be dysfunctional in many different ways, but our armamentarium for fixing them is quite limited. The most common mechanism of action for FDA-approved drugs is inhibition [1] , but there are many other possible perturbation types whose potential remains unrealized.

General Proximity is a seed-stage drug discovery company developing a novel platform technology to solve this problem. We make bifunctional drugs that induce the modification of drug targets by existing cellular machinery (rather than through direct modulation by the drug, the classical approach).

Historically, the development of technologies that allow one to push new buttons in biology has been an incredibly fertile field for the discovery of new medicines[ 2 , 3 , 4 ], and our technology holds the same promise.

The Position We are seeking a medicinal chemist to be a member of our Chemistry/Drug Discovery Team. In this position, you will work with both our Chemistry and Platform Teams in the development of our core drug discovery technology and the generation of a completely novel class of therapeutics.

Your responsibilities will include designing and optimizing first-in-class bifunctional molecules, assessing SAR to inform iterative medicinal chemistry optimization, supervising synthetic efforts with CRO partners, performing and analyzing in cellulo assays, collaborating with our Drug Discovery and IP teams on patent applications, and contributing mechanistic insight on lead drug molecules.

About You High Agency. Initiative, independence, and self-accountability are some of our most valued traits.

Enthusiastic. We love people who are excited about what they are doing and are generally attempting to build a high-energy team.

Intensity and Grit. Early-stage startups are hard. Drug discovery is doubly so. We are looking for candidates who have a demonstrated ability to stick with complex problems for the long haul, with a team that has your back along the way.

Prosocial. We are here to create life-saving medicines for the patients who need it most. You should be, too.

Qualifications & Nice-To-Haves

PhD in Medicinal Chemistry, Chemical Biology, Pharmacology, or related field. Industry experience is desirable, but the ability to work hard and learn fast is more important to us. Deep understanding of small-molecule drug discovery and its relationship to human disease. Able to work fluently at the interface of chemistry and biology. Top-notch written and oral communication skills.

Strong experience in:

Design, synthesis, and optimization of induced proximity medicines (e.g. PROTACs or other IPMs) Hit-to-lead and lead optimization campaigns Multi-step organic synthesis, with a proven ability to design and execute complex synthetic routes toward drug-like small molecules Medicinal chemistry optimization: SAR, PK/PD, and strong working knowledge of DMPK principles Chemical biology techniques including mammalian cell culture, cell-based assays (e.g., cytotoxicity, transfections, stable cell line generation, co-IP), and PPI assays (e.g., BRET, APEX/BioID, AlphaScreen); computational chemistry experience also welcomed

Nice to have:

HTS and phenotypic assay development Proteomics experience: PTM analysis, chemo-proteomic target deconvolution, etc. Computational or molecular dynamics drug discovery experience DEL experience Experience managing synthetic chemistry CRO teams Prior experience on teams that have successfully advanced research to the clinic

Benefits

Strong equity incentives. We are looking for candidates who will bring a strong sense of ownership to drive their project areas forward, and we believe that you deserve to be compensated accordingly. Top tier medical, dental, and vision coverage + One Medical membership. 401(k) retirement plans. Education and health/fitness incentive programs. Meditation retreats—do a ten-day Vipassana retreat without counting towards vacation days. Reading budget! We will buy you books. 📚 Located in the MBC BioLabs at 135 Mississippi Street, an entrepreneurial hub full of the best scientists and operators the Bay Area has to offer. Our lab is a very short walk from the 22nd St Caltrain Station and a number of wonderful restaurants and cafés.

About Us Work Hard/Play Hard. We believe time is our most valuable commodity, so we strive to create a culture that reflects this. We won’t drag you through unnecessary meetings or email you at 7 PM on a Saturday. When we're at work, we're there to get things done, and when we're off, we're really off. 🌴

Strong Communication. We like well-written documents over PowerPoints, OKRs over vague mission statements, and weekly one-on-ones over yearly reviews.

Writing First. We have a "writing-first" culture. We believe that clarity of writing reflects clarity of thinking and that the benefits of well-written documentation in a scientific environment are innumerable: democratization of ideation and decision-making, increased reproducibility, quicker scaling and onboarding, and better company-wide alignment, to name a few.

Growth. As an early-stage startup, we value scientists with an independent, can-do attitude. The more hats you can wear, the better. Our job as employers is to put you in positive feedback loops so you can grow in the direction of your choosing.

Title and compensation commensurate with experience. Applications from candidates of diverse backgrounds, women, and members of underrepresented minority groups are particularly welcomed. We look forward to hearing from you. :)

More info at jobs.generalproximity.bio