Ready-To-Go Assays

Cutting-Edge & Cost-Efficient Services For Multiple Drug Targets

Biophysical & Biochemical Services to Characterize Target Interaction

Established Assays

Optimized assay conditions

Flexible

Single/multiple assays in parallel

Cost-effective

High quality data

Fast Turnaround Time

Less than 2 weeks

nanoDSF – MST – SPR – ADP-Glo – Nucleotide exchange

Protein Supply

Established protein constructs in-house

Tailored high quality assay grade  proteins

Protein QC: SDS-PAGE, aSEC, MS

Complete protein supply included

Assay Initiation & Measurements

Established assay conditions

Established labeling/coupling method

Published tool compounds

Up to 3 Tm/ Kds / IC50s included

Results & Report

A tabulated report included

Extended report available including  measured curves, assay conditions,  analysis and scientific summary in  pdf-format

Biophysical Assays covering a Broad Range of Drug Targets

TargetUniProt IDPPMSTnanoDSFSPRBiochemical Assay
CDK7P50613_
CRBN/DDB1Q96SW2/Q16531developing_
cRELQ96HD1__
DOCK5Q9H7D0nucleotide exchange
GLUT1P11166__
GRB2P62993__
KRASP01116nucleotide exchange
MALT1Q9UDY8_
MAP4K1Q92918developingADP Glo
NLRP3Q96P20developingADP Glo
NRASP01111nucleotide exchange
P2RX3P56373__
p38Q15759__
PolQO75417__
SHP2Q06124__
SMARCA2P51531developingADP Glo
SOS1Q07889_nucleotide exchange
STAT3P40763__
STAT4Q14765___
STAT6P42226_
STINGQ86WV6_
USP7Q93009_
WRNQ14191_

Case Study: biophysical assays to identify novel K-RAS inhibitors

K-RAS is a member of the RAS protein family – GTPases which are involved in signaling processes leading to cell growth and proliferation. Oncogenic variants contribute to 25% of cancers including colorectal and lung cancer. This makes the RAS family of proteins important targets for cancer treatment. After 30 years of research, the recently developed K-RAS inhibitor (Canon et al., 2019) opened the door for promising strategies to target this protein family.

To support and accelerate drug development campaigns to identify novel K-RAS inhibitors, WuXi AppTec offers a platform for small molecule hit-finding and lead optimization including biophysical assays and structure biology services based on established systems.

Protein Production

  • Broad variety of constructs for biophysical assays and crystallography established including,
    • wild type
    • G12C, G12D, G12V
    • G13D
    • “Cys-light” variants for covalent inhibitors
  • Nucleotide exchange protocols established to provide K-RAS variants loaded with GDP and alternative nucleotide analogues such as GTPyS or GMPPNG GDP
  • Characterization and optimization of covalent complex formation using HPLC-MS
  • Related targets protein interaction partners such as SOS1 and Raf available

Biophysical assays for different K-RAS variants established as “Ready-to-Go”

nanoDSF

Nucleotide exchange assay

Labeled MST

GFP-KRAS Fusion

MST in eukaryotic celllysates

Crystallography

  • Established co-crystallization system for covalent and non-covalent small molecule inhibitors
  • Non-covalent and covalent inhibitors; GDP and non-hydrolysable GTP analog bound states
  • Rapid data collection – K-RAS data sets up to 1.3 Å resolution collected in-house on a Bruker MetalJet
  • Established crystallization system for related targets e.g.: SOS1, K-RAS-SOS1 complex