Payload Information

General Information of This Payload
Payload ID
PAY0WXPEV
Name
GRM cpd 64
Synonyms
GRM cpd 64
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Target(s) Glucocorticoid receptor (NR3C1)
 Target Info 
Structure
Formula
C35H37F2NO6
Isosmiles
CC(c1ccc(C2OC3CC4C(CC(O)C5(F)C4CC(F)C4=CC(=O)C=CC45C)C3(C(=O)CO)O2)cc1)c1cccc(N)c1
InChI
InChI=1S/C35H37F2NO6/c1-18(21-4-3-5-22(38)12-21)19-6-8-20(9-7-19)32-43-31-14-24-25(34(31,44-32)30(42)17-39)16-29(41)35(37)26(24)15-28(36)27-13-23(40)10-11-33(27,35)2/h3-13,18,24-26,28-29,31-32,39,41H,14-17,38H2,1-2H3
InChIKey
TXDLLWDVUPWMTK-UHFFFAOYSA-N
Pharmaceutical Properties
Molecule Weight
605.678
Polar area
119.08
Complexity
44
xlogp Value
4.6734
Heavy Count
44
Rot Bonds
5
Hbond acc
7
Hbond Donor
3
The activity data of This Payload
Standard Type Value Units Cell line Disease Model Cell line ID Reference
Glucocorticoid response element reporter EC50 0.0003 uM Undisclosed Undisclosed Undisclosed [1]
Glucocorticoid Receptor binding IC50 0.009 uM Undisclosed Undisclosed Undisclosed [1]
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
Anti-TNF ADC 134 [Investigative]
 ADC Info 
Obtained from the Model Organism Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data P1NP inhibition
25.00%
Positive TNF expression (TNF+++/++)
Method Description
In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 3 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess P1NP level.

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In Vivo Model Acute contact hypersensitivity (CHS) model
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data P1NP inhibition
58.00%
Positive TNF expression (TNF+++/++)
Method Description
In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 10 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess P1NP level.

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In Vivo Model Acute contact hypersensitivity (CHS) model
Experiment 3 Reporting the Activity Date of This ADC [2]
Efficacy Data Ear swelling inhibition
72.00%
Positive TNF expression (TNF+++/++)
Method Description
In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 3 mg/kg once prior to FITC sensitization.
In Vivo Model Fluorescein isothiocyanate (FITC)-induced CHS model
Experiment 4 Reporting the Activity Date of This ADC [2]
Efficacy Data Ear swelling inhibition
94.00%
Positive TNF expression (TNF+++/++)
Method Description
In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 10 mg/kg once prior to FITC sensitization.
In Vivo Model Fluorescein isothiocyanate (FITC)-induced CHS model
Experiment 5 Reporting the Activity Date of This ADC [2]
Efficacy Data Corticosterone inhibition
36.00%
Positive TNF expression (TNF+++/++)
Method Description
In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 3 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess corticosterone level.

   Click to Show/Hide
In Vivo Model Acute contact hypersensitivity (CHS) model
Experiment 6 Reporting the Activity Date of This ADC [2]
Efficacy Data Corticosterone inhibition
74.00%
Positive TNF expression (TNF+++/++)
Method Description
In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 10 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess corticosterone level.

   Click to Show/Hide
In Vivo Model Acute contact hypersensitivity (CHS) model
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Effective Concentration (EC50)
0.80 ng/mL
Positive TNF expression (TNF+++/++)
Method Description
All the DAR purified ADCs were screened in both the TNF-expressing and wild-type K562 GRE reporter cell assay to confirm that their activity was consistent with ADCs having heterogeneous average DAR.
In Vitro Model Chronic myelogenous leukemia K-562 cells (TNF expression) CVCL_0004
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Effective Concentration (EC50)
10.70 ug/mL
Negative TNF expression (TNF-)
Method Description
All the DAR purified ADCs were screened in both the TNF-expressing and wild-type K562 GRE reporter cell assay to confirm that their activity was consistent with ADCs having heterogeneous average DAR.
In Vitro Model Chronic myelogenous leukemia K-562 cells CVCL_0004
References
Ref 1 Discovery of ABBV-3373, an Anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody Drug Conjugate. J Med Chem. 2022 Dec 8;65(23):15893-15934.
Ref 2 Discovery of ABBV-3373, an Anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody Drug Conjugate. J Med Chem. 2022 Dec 8;65(23):15893-15934.

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