D16-M1P2

D16-M1P2 : Degrader (PROTAC) of PKMYT1

Structure

SERP Rating

In Cells

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In Model Organisms

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Information

PKMYT1

Degrader (PROTAC)

10 nM, up to 100 nM hock effect observed around 1000 nM
Reviewer recommended concentration: 30-50 nM

In Vitro Validations

Uniprot ID: Q99640

Target Class: Kinase

Target SubClass: Ser/Thr kinase

Potency: IC50

Potency Value: 7.6 nM

Potency Assay: PKMYT1 ADP-Glo assay

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

Target aliases:

Membrane-associated tyrosine- and threonine-specif ...

DOI Reference: 10.1038/s41467-025-65796-8

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): KinomeScan of 403 non-mutant kinases performed at 1 uM.

Probe Selectivity in Vitro:

Only 4 of the 403 kinases tested, including PKMYT1, exceeded 65% inhibition at 1000 nM (130× its enzymatic IC50). Further validation of the 3 off-targets, BRAF, RAF1, and SRC, revealed that D16-M1P2 exhibited over 50-fold selectivity for PKMYT1.

Potency assay, off target (cells): D16-M1P2 was profiled in HCC1569 cells following 8-hour treatment with 10 and 100 nM. Analysis quantified 132,593 unique peptides representing 8,177 proteins. PKMYT1 was significantly decreased at both 10 nM and 100 nM treatments.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Figure 3b-c suggests that 10-100 nM seems to be a good window for potent PKMYT1 degradation. However, significant degradation of pCDK1 becomes visible at ca. 100nM PROTAC concentration, so the optimum is probably somewhere in between. This seems further supported by data in Figure 3d, though assessment of time dependent degradation at intermediate concentrations would have been useful. 1 nM is a bit low and lead to a modest Dmax, while 100nM reveals the same off-target mentioned above. A few tens of nM might strike the right balance between high Dmax and selectivity.

(last updated: 12 Feb 2026 )