Understanding and exploiting druggable conformations
Proteins adopt a variety of conformations to exert their biological function. This conformational flexibility implies the variation of the size and availability of binding sites, which paves the way for designing drugs with distinct affinity and selectivity.
Drug-target interactions often entail conformational rearrangements in one or both of the binding partners. Several mechanisms explain this: compounds capable of inducing conformational changes in the target, compounds that bind exclusively to specific conformations or molecules that form covalent complexes.
Assessing the parameters that define the steps of the binding mechanism is pivotal for the successful optimization of promising compounds.
- Obtain structural information in the absence of crystal structures.
- Enhanced decision-making: Ideal hit-to-lead and lead optimization tool to exploit protein flexibility.
- Discriminate between irreversible and reversible compounds. Clearly identify simple reversible compounds, reversible compounds that bind to specific conformations or trigger conformational changes in the target, and irreversible compounds.
- Understand PK/PD disconnects: Kinetic profiling often bridges the gap between PK/PD prediction and observation.
- Build better models: PK/PD models that integrate kinetics better predict target engagement, drug dose and treatment schedule.
COVALfinder® is a kinetic screening platform that provides in-depth understanding of the binding mechanism of reversible and irreversible drugs to iterate medicinal chemistry, understand PK/PD disconnects and build better models to define therapeutic windows.
List of targets ready to use
Our expertise extends beyond kinases to GPCR and other target types.Search our database to discover whether your target is:
- May be possible: We have a strong track record of achievement where others fail! Contact us to find out more.
- Clear line of sight: Establishment requires finalization / validation, which typically takes 2-4 weeks to complete.
- Good to go: Data within 2 weeks of compound receipt.
* Full length and partial length forms are available.
|Target name||Alternative names||KINETICfinder||COVALfinder|
|AAK1||KIAA1048, DKFZp686K16132||Clear line of sight|
|ABL1||ABL, c-ABL1, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL, p150, v-abl||Good to go|
|ABL1 E255K||ABL, c-ABL1, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL, p150, v-abl||Clear line of sight|
|ABL1 G250E||ABL, c-ABL1, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL, p150, v-abl||Clear line of sight|
|ABL1 H396P||ABL, c-ABL1, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL, p150, v-abl||Clear line of sight|
|ABL1 M351T||ABL, c-ABL1, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL, p150, v-abl||Clear line of sight|
|ABL1 Q252H||ABL, c-ABL1, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL, p150, v-abl||Clear line of sight|
|ABL1 Y253F||ABL, c-ABL1, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL, p150, v-abl||Clear line of sight|
|ABL2 (ARG)||ARG, ABL isoform b, ABLL||Good to go|
|ACK (TNK2)||ACK, ACK-1, ACK1, p21cdc42Hs||Clear line of sight|
|ACVR2A||ACTRII, ACTR2, ACVR2||Clear line of sight|
|ACVR2B||ACTRIIB, ActR-IIB, HTX4||Clear line of sight|
|AKT1||AKT1, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA,||Good to go|
|ALK||ALK, CD246, NBLST3||Good to go||May be possible|
|ALK C1156Y||ALK, CD246, NBLST3||Clear line of sight|
|ALK F1174L||ALK, CD246, NBLST3||Clear line of sight|
|ALK L1196M||ALK, CD246, NBLST3||Clear line of sight|
|ALK R1275Q||ALK, CD246, NBLST3||Clear line of sight|
|ALK T1151_L1152insT||ALK, CD246, NBLST3||Clear line of sight|
|ALK1 (ACVRL1)||ALK1, ALK-1, ACVRLK1, HHT, HHT2, ORW2, SKR3, TSR-I||Good to go||May be possible|
How can we help?
Our experienced project manager will work with you to identify the best way forward for your project.