Medicinal Chemistry Integration
The Reaction Oncology Platform

Medicinal Chemistry Integration

Modern drug discovery is a multi-disciplinary team effort for creating small molecules as well as more complex modalities such as dual-target small molecules, protein degraders, or cyclopeptides. A skilled chemistry team is the main driver for developing new chemical entities to create new IP and value for our customers. The Reaction Oncology Platform enables a team approach by bringing together highly skilled chemists and our experienced biologists.

Our Chemistry Partners


Our clients get access to premium chemistry via our partner Symeres. Being Europe‘s best-in-class chemistry provider, Symeres has a stunning track record of successfully creating new APIs used daily in clinics worldwide. Symeres excels in creativity and has over 30 years of chemistry experience to deliver novel small molecules tackling even the most challenging targets.

Symeres capabilities

We have collaborated with Symeres since 2012 on several small molecule oncology programs. Our teams work together seamlessly under one MSA. We take responsibility for all logistical aspects of the project (compound registration and shipping, screening logistics, tracking of stock quantities, etc.), allowing our client to fully focus on the science.


Medinoah is our Chinese chemistry partner with track records of AI modeling, discovery, and cGMP production in the small molecule and PROTAC space. The company was founded in 2008 and has already promoted more than 20 compounds into IND/clinical stages.

As one of the earliest medicinal chemistry providers entering the PROTAC field, Medinoah provides libraries for ligases and linkers to fast-track new PROTAC molecule development. Their access to artificial development resources enables the prediction of binding modes of compounds and targets, reducing the number of screening cycles needed to generate potent and optimized compounds.

A partnership project with Symeres: Development of a novel CDK8 inhibitor with engineered long residence times


  • CDK8 is an oncogene that is frequently upregulated in colorectal cancer
  • Ser/Thr kinase CDK8 depending on Cyclin C
  • Substrates: RNA Pol II, Histone 3, SMAD

Starting point

  • Design and synthesis of new scaffold fragments
  • Exploration of IP-free chemical class of inhibitor
  • Aim for high selectivity
  • Aim for long residence time


Symeres CDK8 compound pocketSymeres CDK8 compound structure

Retro-design: Scaffold growing from the deep pocket towards the ATP binding site

Lead candidate profile

  • After screening 80 scaffold fragments, we identified one hit fragment, which was advanced into the hit-to-lead phase.
  • 4 SAR cycles produced one highly selective lead, which progressed into the lead optimization phase.
  • The lead candidate was tested with DMPK, ADME, and safety assays, as well as cellular and in vivo efficacy studies. After further optimizing, the compound shows biochemical efficacy in the nanomolar range and cellular efficacy in the micromolar range with an excellent selectivity profile.
  • Proof of concept studies on the HCT-116 tumor model yielded a potency of 32 % diminished tumor growth compared to vehicle control. The drug candidate inhibits the phosphorylation of a downstream effector, STAT1, significantly in the tumor tissue.
  • Readouts for pharmacology and safety showed favorable solubility, permeability, and bioavailability parameters. Preliminary safety and toxicology readouts did not produce any signs of adverse effects.


  • The CDK8 drug discovery project successfully helped establish communication, logistics, and decision-making lines between Reaction Biology and our chemistry partner Symeres.

An AI-based approach to creating new PROTACs

Rethinking PROTAC

With Medinoah, our medicinal chemistry partner, and PMRBioinfo, an AI computational company, we created the Rethinking PROTAC drug discovery suite. Medinoah has been one of the earliest CROs pioneering in creating PROTAC and advancing two PROTAC molecules into IND stage. Their extensive pool of degraders, linkers, ligase ligands, and ligand-linker conjugates enables the fast synthesis of PROTAC molecules. Scalable synthesis of PROTACs from milligram to 100+ kilo has been successfully achieved under both GMP/non-GMP conditions.

The AI-powered PROTAC discovery platform will enable the prediction of the binding mode of the ternary complex to significantly reduce the number of compounds and screening cycles needed for the generation of potent and optimized PROTAC molecules.