Payload Information

General Information of This Payload
Payload ID
PAY0OQPXP
Name
GRM cpd 20
Synonyms
GRM cpd 20
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Target(s) Glucocorticoid receptor (NR3C1)
 Target Info 
Structure
Formula
C34H35F2NO6
Isosmiles
CC12C=CC(=O)C=C1C(F)CC1C3CC4OC(c5ccc(Cc6cccc(N)c6)cc5)OC4(C(=O)CO)C3CC(O)C12F
InChI
InChI=1S/C34H35F2NO6/c1-32-10-9-22(39)13-26(32)27(35)15-25-23-14-30-33(29(41)17-38,24(23)16-28(40)34(25,32)36)43-31(42-30)20-7-5-18(6-8-20)11-19-3-2-4-21(37)12-19/h2-10,12-13,23-25,27-28,30-31,38,40H,11,14-17,37H2,1H3
InChIKey
DONRJZQEXQMCRR-UHFFFAOYSA-N
Pharmaceutical Properties
Molecule Weight
591.651
Polar area
119.08
Complexity
43
xlogp Value
4.1124
Heavy Count
43
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±0.0002 uM Undisclosed Undisclosed Undisclosed [1]
Glucocorticoid Receptor binding IC50 0.009±0.007 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 126 [Investigative]
 ADC Info 
Obtained from the Model Organism Data
Click To Hide/Show 8 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Paw swelling AUC
92.00%
Positive TNF expression (TNF+++/++)
Method Description
To evaluate the impact of the anti-mTNF GRM ADCs on inflammation in a chronic inflammatory setting,we progressed several ADCs into a mouse collagen-induced arthritis (mCIA) model. A single 3 mg/kg dose of the ADC was given at the first clinical signs of disease,a time point of intervention where anti-TNF treatment has a moderate impact.
In Vivo Model Collagen-induced arthritis (mCIA) model
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Paw swelling AUC
100.00%
Positive TNF expression (TNF+++/++)
Method Description
To evaluate the impact of the anti-mTNF GRM ADCs on inflammation in a chronic inflammatory setting,we progressed several ADCs into a mouse collagen-induced arthritis (mCIA) model. A single 10 mg/kg dose of the ADC was given at the first clinical signs of disease,a time point of intervention where anti-TNF treatment has a moderate impact.
In Vivo Model Collagen-induced arthritis (mCIA) model
Experiment 3 Reporting the Activity Date of This ADC [2]
Efficacy Data P1NP inhibition
3.00%
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 4 Reporting the Activity Date of This ADC [2]
Efficacy Data P1NP inhibition
32.00%
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 5 Reporting the Activity Date of This ADC [2]
Efficacy Data Ear swelling inhibition
73.00%
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 6 Reporting the Activity Date of This ADC [2]
Efficacy Data Ear swelling inhibition
88.00%
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 7 Reporting the Activity Date of This ADC [2]
Efficacy Data Corticosterone inhibition
35.00%
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.

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In Vivo Model Acute contact hypersensitivity (CHS) model
Experiment 8 Reporting the Activity Date of This ADC [2]
Efficacy Data Corticosterone inhibition
71.00%
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.

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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)
0.03 ug/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)
50.00 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
Anti-TNF ADC 125 [Investigative]
 ADC Info 
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)
0.03 ug/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)
11.90 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
Anti-TNF ADC 109 [Investigative]
 ADC Info 
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)
0.12 ug/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) > 50.00 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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