Payload Information

General Information of This Payload

Payload ID	PAY0ECADG
Name	GRM cpd 25
Synonyms	GRM cpd 25 Click to Show/Hide
Target(s)	Glucocorticoid receptor (NR3C1)			Target Info
Structure
Structure	3D MOL		2D MOL
Formula	C33H34FNO6S
Isosmiles	CC12C=CC(=O)C=C1CCC1C3CC4OC(c5ccc(Sc6cccc(N)c6)cc5)OC4(C(=O)CO)C3CC(O)C12F
InChI	InChI=1S/C33H34FNO6S/c1-31-12-11-21(37)13-19(31)7-10-25-24-15-29-32(28(39)17-36,26(24)16-27(38)33(25,31)34)41-30(40-29)18-5-8-22(9-6-18)42-23-4-2-3-20(35)14-23/h2-6,8-9,11-14,24-27,29-30,36,38H,7,10,15-17,35H2,1H3
InChIKey	TUHASGVCCAPLQA-UHFFFAOYSA-N
Pharmaceutical Properties	Molecule Weight	591.701	Polar area	119.08
	Complexity	42	xlogp Value	4.7248
	Heavy Count	42	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	0.0004	uM	Undisclosed	Undisclosed	Undisclosed	[1]
Glucocorticoid Receptor binding IC50	0.013	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 127 [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	34.00%	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. Click to Show/Hide
In Vivo Model	Acute contact hypersensitivity (CHS) model
Experiment 2 Reporting the Activity Date of This ADC				[2]
Efficacy Data	P1NP inhibition	57.00%	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. Click to Show/Hide
In Vivo Model	Acute contact hypersensitivity (CHS) model
Experiment 3 Reporting the Activity Date of This ADC				[2]
Efficacy Data	Ear swelling inhibition	68.00%	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	0.00%	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	18.00%	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)	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 113 [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)	0.20 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)	3.10 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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Citation

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Correspondence

Prof. Feng ZHU (zhufeng@zju.edu.cn)

Prof. Xiaowu DONG (dongxw@zju.edu.cn)

Prof. Luo FANG (fangluo@zjcc.org.cn)