D16-M1P2 | D16-M1P2 : Degrader (PROTAC) of PKMYT1
RATINGS:
Cellular Use: (1 reviews)

In Model Organisms: (1 reviews)
Chemical Information
Vendors

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
PKMYT1
  • IC50:7.6 nM
  • EC50:12 nM
  • DC50:0.7 nM
Degrader (PROTAC)
30-50 nM
10 nM, up to 100 nM hock effect observed around 1000 nM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
KinomeScan of 403 non-mutant kinases performed at 1 uM.
Selectivity Assessment Description:
Only 4 of the 403 kinases tested, including PKMYT1, exceeded 65% inhibition at 1000 nM (130× its enz ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
D16-M1P2 was profiled in HCC1569 cells following 8-hour treatment with 10 and 100 nM. Analysis quant ...

Potency
Cellular
In Vitro

PKMYT1

Mode of Action: Degrader (PROTAC)

Structure-Activity-Relationship data available? Yes

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

In Vivo Validations

Mouse
Dose: 1 mg/Kg IV, 40 mg/Kg PO
Route of delivery: Intravenous, Oral
Plasma half life: 3.6 h
Systemic clearance: 80.2 mL/min/Kg
Cmax: 1181 ng/mL
Area Under the Curve:: 7436 h*ng/mL
Bioavailability: 91.3%
Volume of Distribution at Steady-State: 6.6 L/Kg

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

Rat
Dose: 1 mg/Kg IV, 20 mg/Kg PO
Route of delivery: Intravenous, Oral
Plasma half life: 7.7 h
Systemic clearance: 17.6 mL/min/Kg
Cmax: 2269 ng/mL
Area Under the Curve:: 29851 h*ng/mL
Bioavailability: 166.5%
Volume of Distribution at Steady-State: 3.7 L/Kg

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

Dog
Dose: 1 mg/Kg IV, 5 mg/Kg PO
Route of delivery: Intravenous, Oral
Plasma half life: 6.3 h
Systemic clearance: 7.2 mL/min/Kg
Cmax: 583 ng/mL
Area Under the Curve:: 7461 h*ng/mL
Bioavailability: 67.9%
Volume of Distribution at Steady-State: 3.3 L/Kg

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

Monkey (Cynomolgus)
Dose: 1 mg/Kg IV, 10 mg/Kg PO
Route of delivery: Intravenous, Oral
Plasma half life: 10.9 h
Systemic clearance: 19.3 mL/min/Kg
Cmax: 144 ng/mL
Area Under the Curve:: 1721 h*ng/mL
Bioavailability: 20.5%
Volume of Distribution at Steady-State: 5.1 L/Kg

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

Negative Control Compounds

D16-NMe-M1P2
Notes: D16-NMe-M1P2 retained similar PKMYT1 enzymatic inhibition (IC50 of 8.5 nM) and intracellular target engagement (EC50 of 8.0 nM) to D16-M1P2 with DC50 >1000 nM.
SMILES: CC1=C(C(=C(C=C1)O)C)C2=C(C#N)C3=C(N=C2)NC(=C3)C4=CN=C(N=C4)N5CCC6(CC5)CC(CO6)N7CCN(CC7)C8=CC=C(C=C8F)N[C@H]9CCC(=O)N(C)C9=O

Chemical Information

Coming Soon...

References

Cross References

Expert Reviews


(on 12 Feb 2026 )
Cellular Use Rating
In Model Organisms
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...
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