VEPDEGESTRANT | VEPDEGESTRANT : Degrader (PROTAC) of ESR1
RATINGS:
Cellular Use: (0 reviews)

In Model Organisms: (0 reviews)
Vendors

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 )

References

Cross References

Expert Reviews


No SERP comments found for VEPDEGESTRANT

Probe VEPDEGESTRANT is in the process of SERP review.

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