SIAIS001

SIAIS001 : Degrader (PROTAC) of ALK

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 ratings)

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Probe SIAIS001 is in the process of SERP review.

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Information

Degrader (PROTAC)

100 nM

In Vitro Validations

Uniprot ID: Q9UM73

Target Class: Kinase

Target SubClass: TK

Potency: IC50

Potency Value: 0.9 nM

Potency Assay: Inhibition of recombinant ALK

PDB ID for probe-target interaction (3D structure): --

Target aliases:

ALK tyrosine kinase receptor, ALK, ALK_HUMAN, Anap ...

DOI Reference: 10.1016/j.ejmech.2021.113335

In Cell Validations

In Vivo Data

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This ALK PROTAC is unique in being constructed from Alectinib with a phthalimide degrader functionality. The probe inhibits ALK activity in cells and convincingly induces ALK degradation, although with a maximal effect size ca. 70% (ie, signficant ALK remains). High microsomal stability is noted, and IP dosing of rats at 2 mpk or PO dosing of rats at 10 mpk achieves plasma levels expected to target ALK, but no PD markers or evidence of target engagement/degradation in vivo are available. Nonetheless, this is a credible probe that uses a distinct warhead to induce degradation of ALK (including to a lesser extent G1202R mutant ALK).

(last updated: 10 Apr 2022 )