De-risking irreversible drug discovery

Irreversible inhibition is time dependent and intrinsically related to both the affinity (KI) and reactivity (kinact) of the covalent inhibitor. These data are more relevant to the optimization of irreversible inhibitors than IC50 values, enabling drug hunters to properly identify irreversible compounds, rank structure-activity relationships (SAR), interpret selectivity and define in vivo target occupancy.

Applications

  • Easier decision-making: An ideal hit-to-lead and lead optimization tool to facilitate parallel improvement of both compound binding and covalent bond formation.
  • Selectivity profiling for irreversible drugs: Evaluating inactivation efficiency (kinact/KI) accurately defines the time-dependent effects of covalent binding and enables the safety profile of irreversible drugs to be more rigorously assessed.
  • Build better models: PK/PD models that integrate kinetics better predict target engagement, drug dose and treatment schedule.

    Technology

    COVALfinder®

    COVALfinder® is a kinetic screening platform that provides in-depth understanding of the binding mechanism of reversible, reversible covalent 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) TNK2, ACK-1, ACK1, p21cdc42Hs Good to go
    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.