Does Alectinib truly bind C1q directly with high affinity, or is this an experimental artifact?

molecular-biology partially_addressed composite 55%
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Composite
55%
Novelty
40%
Mechanistic
—
Druggability
—
Priority
90%
Importance
60%
Tractability
95%
Market price
50%

Description

The fundamental premise remains unvalidated despite extensive mechanistic speculation. Independent validation using purified proteins and orthogonal binding assays is essential before pursuing mechanistic studies. This determines whether any C1q-related effects are direct or indirect.

Source: Debate session sess_SDA-2026-04-16-gap-pubmed-20260410-095709-4e97c09e (Analysis: SDA-2026-04-16-gap-pubmed-20260410-095709-4e97c09e)

Resolution criteria

Resolution requires: (1) surface plasmon resonance (SPR) or biolayer interferometry (BLI) measuring binding affinity (KD) of alectinib to purified human C1q at concentrations ≤10 μM; (2) at least two orthogonal assays (SPR, ITC, AlphaLISA) confirming direct interaction; (3) negative control with unrelated kinase inhibitor showing no C1q binding. Previously reported binding must be reproduced in an independent lab. High background in assay buffers disqualifies the claim.