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VEPDEGESTRANT | VEPDEGESTRANT : Degrader (PROTAC) of ESR1
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

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Targets Biochemical/Biophysical Potency Cellular Potency
ESR1 (Mutant:WT, Y537S, D538G,Y537C, Y537N, E380Q, L536P, V422del)
  • IC50:0.99 nM
  • IC50:~100 nM
  • DC50: 0.9 nM
  • GI50: 3.3 nM
  • GI50:4.5 nM
  • IC50:1.1 nM
Degrader (PROTAC)
100 nM

Selectivity

In Cell Selectivity Assessment
Potency Assay Off-Target:
Tandem mass tag–based proteomics was used to profile the MCF7 proteome following a 7-hour incubation ...
Selectivity Assessment Description:
39,139 unique peptides were quantified, representing 10,387 proteins. Analysis revealed the ESR1 enc ...
In Vitro Selectivity Assessment
Potency Assay Off-Target:
selectivity of vepdegestrant binding was assessed in the Eurofins SafetyScreen87 panel consisting of ...
Selectivity Assessment Description:
More than 50% binding inhibition by vepdegestrant was observed relative to the cognate ligand for ER ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
Cellular degradation of IKZF1, IKZF3, GSPT1, or CK1α, and SALL4 was assessed and was considered irre ...

Potency
Cellular
In Vitro

ESR1 (Mutant:WT, Y537S, D538G,Y537C, Y537N, E380Q, L536P, V422del)

Mode of Action: Degrader (PROTAC)

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1002/cmdc.202501111

In Vivo Validations

Mouse
Dose: 5 mg/kg
Route of delivery: Oral
Plasma half life: 3.6–4.1 h
Cmax: 0.39 ± 0.13 µg/mL
Tmax: 1.00 ± 0.00 h
Area Under the Curve:: 2.91 ± 0.71 µg·h/mL
Bioavailability: 17.91% ± 4.35%

DOI Reference: 10.1002/cmdc.202501111

Rat
Dose: 5 mg/Kg
Route of delivery: Oral
Plasma half life: 3.6–4.1 h
Cmax: 0.11 ± 0.04 µg/mL
Tmax: 3.20 ± 2.95 h
Area Under the Curve:: 1.15 ± 0.45 µg·h/mL
Bioavailability: 24.12% ± 9.39%

DOI Reference: 10.1002/cmdc.202501111

Negative Control Compounds

A5927
Notes: CRBN-Inactive
SMILES: CN1C(=O)CCC(C1=O)N2CC3=C(C=CC(=C3)N4CCN(CC4)CC5CCN(CC5)C6=CC=C(C=C6)[C@H]7[C@H](CCC8=CC(=CC=C87)O)C9=CC=CC=C9)C2=O
A9060
Notes: ER-Inactive
PubChem ID: C1=CC=C(C=C1)[C@@H]2CCC3=CC(=CC=C3[C@@H]2C4=CC=C(C(=C4)F)N5CCC(CC5)CN6CCN(CC6)C7=CC=C8C(=C7)CN([C@H]9CCC(=O)NC9=O)C8=O)O

Chemical Information

Molecular Formula C45H49N5O4
SMILEs O=C1CC[C@H](N2Cc3cc(N4CCN(CC5CCN(c6ccc([C@@H]7c8ccc(O)cc8CC[C@@H]7c7ccccc7)cc6)CC5)CC4)ccc3C2=O)C(=O)N1
InChI InChI=1S/C45H49N5O4/c51-37-12-15-39-33(27-37)8-13-38(31-4-2-1-3-5-31)43(39)32-6-9-35(10-7-32)48-20-18-30(19-21-48)28-47-22-24-49(25-23-47)36-11-14-40-34(26-36)29-50(45(40)54)41-16-17-42(52)46-44(41)53/h1-7,9-12,14-15,26-27,30,38,41,43,51H,8,13,16-25,28-29H2,(H,46,52,53)/t38-,41+,43+/m1/s1
Molecular weight 723.38 Da
AlogP 6.053700000000006
HBond acceptors 9
HBond donors 2
Atoms 103
PAINS * Yes

* This is an automated alert only, and may not necessarily indicate an issue with this probe. ( Learn more about PAINS )

Expert Reviews

by SERP
(on 13 Jul 2026)
Cellular Use Rating
In Model Organisms
The recommended concentrations are suitable for high Dmax in a relatively short time window (few hours to ca. 1 day). Lower concentration and longer treatment may lead to similar degradation potency, depending...
by SERP
(on 4 Aug 2026)
Cellular Use Rating
In Model Organisms
Excellent probe for in vivo and in vitro studies based on potent ER degradation. Studies should be conducted with the two inactive controls provided. Note that the Eurofin safety screen indicates that...
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