Payload Information

General Information of This Payload
Payload ID
PAY0QBKLZ
Name
GRM cpd 26
Synonyms
GRM cpd 26
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Target(s) Glucocorticoid receptor (NR3C1)
 Target Info 
Structure
Formula
C33H33F2NO6S
Isosmiles
CC12C=CC(=O)C=C1C(F)CC1C3CC4OC(c5ccc(Sc6cccc(N)c6)cc5)OC4(C(=O)CO)C3CC(O)C12F
InChI
InChI=1S/C33H33F2NO6S/c1-31-10-9-19(38)12-25(31)26(34)14-24-22-13-29-32(28(40)16-37,23(22)15-27(39)33(24,31)35)42-30(41-29)17-5-7-20(8-6-17)43-21-4-2-3-18(36)11-21/h2-12,22-24,26-27,29-30,37,39H,13-16,36H2,1H3
InChIKey
VHFLAVGGDNGJPS-UHFFFAOYSA-N
Pharmaceutical Properties
Molecule Weight
609.691
Polar area
119.08
Complexity
43
xlogp Value
4.6728
Heavy Count
43
Rot Bonds
5
Hbond acc
8
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 0.0001±0.0002 uM Undisclosed Undisclosed Undisclosed [1]
Glucocorticoid Receptor binding IC50 0.015±0.020 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 128 [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
17.00%
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
53.00%
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
59.00%
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
92.00%
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
23.00%
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 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)
0.03 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)
3.90 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 114 [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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