Payload Information

General Information of This Payload
Payload ID
PAY0DPMMV
Name
3-aminophenyl-hemiasterlin
Synonyms
3-aminophenyl-hemiasterlin
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Structure
Formula
C27H44N4O4
Isosmiles
CC(C)([C@H](NC([C@@H](NC)C(C)(C1=CC=CC(N)=C1)C)=O)C(N([C@@H](C(C)C)/C=C(C(O)=O)\C)C)=O)C
PubChem CID
122467623
InChI
InChI=1S/C27H44N4O4/c1-16(2)20(14-17(3)25(34)35)31(10)24(33)22(26(4,5)6)30-23(32)21(29-9)27(7,8)18-12-11-13-19(28)15-18/h11-16,20-22,29H,28H2,1-10H3,(H,30,32)(H,34,35)/t20-,21-,22-/m1/s1
InChIKey
ILRXQTICSGMLFH-YPAWHYETSA-N
Pharmaceutical Properties
Molecule Weight
488.673
Polar area
124.76
Complexity
911.601856
xlogp Value
3.1792
Heavy Count
35
Rot Bonds
10
Hbond acc
5
Hbond Donor
4
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
Anti-MUC1/EGFR ADC [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 7 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl)
0%
High MUC1 expression (MUC1 +++);Low EGFR expression (EGFR+)
Method Description
Female athymic nude mice with established WISH tumors (3&#45 150 mm3) were treated with a single intravenous (IV) injection 0.1 mg/kg ADC.The effects of treatment on WISH tumor growth and the individual tumor sizes on the day the vehicle control treated tumors reached the study endpoint (> 1,200 mm3) are illustrated.
In Vivo Model WISH xenograft model
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl)
12%
High MUC1 expression (MUC1 +++);Low EGFR expression (EGFR+)
Method Description
Female athymic nude mice with established WISH tumors (3&#45 150 mm3) were treated with a single intravenous (IV) injection 0.3 mg/kg ADC.The effects of treatment on WISH tumor growth and the individual tumor sizes on the day the vehicle control treated tumors reached the study endpoint (> 1,200 mm3) are illustrated.
In Vivo Model WISH xenograft model
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl)
47%
High MUC1 expression (MUC1 +++);Low EGFR expression (EGFR+)
Method Description
Female athymic nude mice with established WISH tumors (3&#45 150 mm3) were treated with a single intravenous (IV) injection 0.75 mg/kg ADC.The effects of treatment on WISH tumor growth and the individual tumor sizes on the day the vehicle control treated tumors reached the study endpoint (> 1,200 mm3) are illustrated.
In Vivo Model WISH xenograft model
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl)
81%
High MUC1 expression (MUC1 +++);Low EGFR expression (EGFR+)
Method Description
Female athymic nude mice with established WISH tumors (3&#45 150 mm3) were treated with a single intravenous (IV) injection 1.5 mg/kg ADC.The effects of treatment on WISH tumor growth and the individual tumor sizes on the day the vehicle control treated tumors reached the study endpoint (> 1,200 mm3) are illustrated. Determined tumor volume after the experiment, measured at day 21.

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In Vivo Model WISH xenograft model
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl) > 100% Moderate MUC1 expression (MUC1++);Low EGFR expression (EGFR+)
Method Description
Female CB17 SCID mice with established OVCAR-3 tumors (3&#45 100 mm3) were treated with a single IV injection of 2.5 mg/kg ADC. Analysis of tumor size on day 28.
In Vivo Model OVCAR-3 xenograft model
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl) > 100% Moderate MUC1 expression (MUC1++);Low EGFR expression (EGFR+)
Method Description
Female CB17 SCID mice with established OVCAR-3 tumors (3&#45 100 mm3) were treated with a single IV injection of 5 mg/kg ADC. Analysis of tumor size on day 28.
In Vivo Model OVCAR-3 xenograft model
Experiment 7 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl) > 100% Moderate MUC1 expression (MUC1++);Low EGFR expression (EGFR+)
Method Description
Female CB17 SCID mice with established OVCAR-3 tumors (3&#45 100 mm3) were treated with a single IV injection of 10mg/kg ADC. Analysis of tumor size on day 28.
In Vivo Model OVCAR-3 xenograft model
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl)
24%
Method Description
Female nude mice with established LUX089 tumors (3&#45 150 mm3) were treated with a single IV injection at day 0 at 10mg/kg ADC. In three ofthe five animals treated in the 10 mg/kg dose group, no tumor was measurable up to day 60, when the experiment was finished.
In Vivo Model NSCLC Patient-derived xenograft (PDX) model LUX089
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl)
69%
Method Description
Female nude mice with established LUX089 tumors (3&#45 150 mm3) were treated with a single IV injection at day 0 at 10mg/kg ADC. In three ofthe five animals treated in the 10 mg/kg dose group, no tumor was measurable up to day 60, when the experiment was finished.
In Vivo Model NSCLC Patient-derived xenograft (PDX) model LUX089
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth lnhibition value (TGl) > 100%
Method Description
Female nude mice with established LUX089 tumors (3&#45 150 mm3) were treated with a single IV injection at day 0 at 10mg/kg ADC. In three ofthe five animals treated in the 10 mg/kg dose group, no tumor was measurable up to day 60, when the experiment was finished.
In Vivo Model NSCLC Patient-derived xenograft (PDX) model LUX089
Revealed Based on the Cell Line Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.09 nM
Low MUC1 expression (MUC1+);High EGFR expression (EGFR+++)
Method Description
A total of 625 cells (MDA-MB-468) in a volume of 25 uL were seeded in a 384-well flat bottom white polystyrene plate the day before the actual assay started. ADC and free drugs were formulated at 2x starting concentration in cell culture medium and filtered through 0.22um cellulose acetate filtered 2 ml centrifuge tubes. Filter sterilized samples were serial diluted (1:3) under sterile conditions and 25 uL of each dilution was added onto cells in triplicates. Plates were cultured at 37 °C in a C02 incubator for 120 hours. For cell viability measurement, 30 uL of Cell Titer-Glo@ reagent (PromegaT M Corp, Madison, WI) was added into each well, and plates processed as per product instructions. Relative luminescence was measured.

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In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.23 nM
Low MUC1 expression (MUC1+);High EGFR expression (EGFR+++)
Method Description
A total of 625 cells (NCI-H292) were plated in 90 ul cell culture medium per well of a 96-well black/clear flat bottom TC-treated imaging microplate and cultured overnight. A ten-fold starting concentration of ADCs, a respective serial dilution (1:4) were prepared in cell culture medium briefly before use. Wells were supplied with 10 ul ADC or compound solution. Treatment was performed in technical triplicates. The plates were subsequently incubated for 144h. For subsequent cell viability measurement, 100 ul Cell Titer-Glo reagent was pipetted in each well, and plates were further processed according the manufacturer's instructions.

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In Vitro Model Lung adenocarcinoma HCC827 cells CVCL_2063
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.41 nM
Moderate MUC1 expression (MUC1++);Low EGFR expression (EGFR+)
Method Description
A total of 625 cells (OVCAR-3) in a volume of 25 uL were seeded in a 384-well flat bottom white polystyrene plate the day before the actual assay started. ADC and free drugs were formulated at 2x starting concentration in cell culture medium and filtered through 0.22um cellulose acetate filtered 2 ml centrifuge tubes. Filter sterilized samples were serial diluted (1:3) under sterile conditions and 25 uL of each dilution was added onto cells in triplicates. Plates were cultured at 37 °C in a C02 incubator for 120 hours. For cell viability measurement, 30 uL of Cell Titer-Glo@ reagent (PromegaT M Corp, Madison, WI) was added into each well, and plates processed as per product instructions. Relative luminescence was measured.

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In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.83 nM
Low MUC1 expression (MUC1+);Low EGFR expression (EGFR+)
Method Description
A total of 625 cells (NCI-H292) were plated in 90 ul cell culture medium per well of a 96-well black/clear flat bottom TC-treated imaging microplate and cultured overnight. A ten-fold starting concentration of ADCs, a respective serial dilution (1:4) were prepared in cell culture medium briefly before use. Wells were supplied with 10 ul ADC or compound solution. Treatment was performed in technical triplicates. The plates were subsequently incubated for 144h. For subsequent cell viability measurement, 100 ul Cell Titer-Glo reagent was pipetted in each well, and plates were further processed according the manufacturer's instructions.

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In Vitro Model Lung adenocarcinoma NCI-H1975 cells CVCL_1511
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
1.1 nM
Low MUC1 expression (MUC1+);Moderate EGFR expression (EGFR++)
Method Description
A total of 625 cells (NCI-H292) were plated in 90 ul cell culture medium per well of a 96-well black/clear flat bottom TC-treated imaging microplate and cultured overnight. A ten-fold starting concentration of ADCs, a respective serial dilution (1:4) were prepared in cell culture medium briefly before use. Wells were supplied with 10 ul ADC or compound solution. Treatment was performed in technical triplicates. The plates were subsequently incubated for 144h. For subsequent cell viability measurement, 100 ul Cell Titer-Glo reagent was pipetted in each well, and plates were further processed according the manufacturer's instructions.

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In Vitro Model Lung mucoepidermoid carcinoma NCI-H292 cells CVCL_0455
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
1.4 nM
High MUC1 expression (MUC1 +++);Low EGFR expression (EGFR+)
Method Description
A total of 625 cells (WISH) in a volume of 25 uL were seeded in a 384-well flat bottom white polystyrene plate the day before the actual assay started. ADC and free drugs were formulated at 2x starting concentration in cell culture medium and filtered through 0.22um cellulose acetate filtered 2 ml centrifuge tubes. Filter sterilized samples were serial diluted (1:3) under sterile conditions and 25 uL of each dilution was added onto cells in triplicates. Plates were cultured at 37 °C in a C02 incubator for 120 hours. For cell viability measurement, 30 uL of Cell Titer-Glo@ reagent (PromegaT M Corp, Madison, WI) was added into each well, and plates processed as per product instructions. Relative luminescence was measured.

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In Vitro Model Endocervical adenocarcinoma WISH cells CVCL_1909
Anti-EGFR ADC [Investigative]
 ADC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.04 nM
Low MUC1 expression (MUC1+);Low EGFR expression (EGFR+)
Method Description
A total of 625 cells (NCI-H292) were plated in 90 ul cell culture medium per well of a 96-well black/clear flat bottom TC-treated imaging microplate and cultured overnight. A ten-fold starting concentration of ADCs, a respective serial dilution (1:4) were prepared in cell culture medium briefly before use. Wells were supplied with 10 ul ADC or compound solution. Treatment was performed in technical triplicates. The plates were subsequently incubated for 144h. For subsequent cell viability measurement, 100 ul Cell Titer-Glo reagent was pipetted in each well, and plates were further processed according the manufacturer's instructions.

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In Vitro Model Lung adenocarcinoma NCI-H1975 cells CVCL_1511
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.06 nM
Low MUC1 expression (MUC1+);High EGFR expression (EGFR+++)
Method Description
A total of 625 cells (NCI-H292) were plated in 90 ul cell culture medium per well of a 96-well black/clear flat bottom TC-treated imaging microplate and cultured overnight. A ten-fold starting concentration of ADCs, a respective serial dilution (1:4) were prepared in cell culture medium briefly before use. Wells were supplied with 10 ul ADC or compound solution. Treatment was performed in technical triplicates. The plates were subsequently incubated for 144h. For subsequent cell viability measurement, 100 ul Cell Titer-Glo reagent was pipetted in each well, and plates were further processed according the manufacturer's instructions.

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In Vitro Model Lung adenocarcinoma HCC827 cells CVCL_2063
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.13 nM
Moderate MUC1 expression (MUC1++);Low EGFR expression (EGFR+)
Method Description
A total of 625 cells (OVCAR-3) in a volume of 25 uL were seeded in a 384-well flat bottom white polystyrene plate the day before the actual assay started. ADC and free drugs were formulated at 2x starting concentration in cell culture medium and filtered through 0.22um cellulose acetate filtered 2 ml centrifuge tubes. Filter sterilized samples were serial diluted (1:3) under sterile conditions and 25 uL of each dilution was added onto cells in triplicates. Plates were cultured at 37 °C in a C02 incubator for 120 hours. For cell viability measurement, 30 uL of Cell Titer-Glo@ reagent (PromegaT M Corp, Madison, WI) was added into each well, and plates processed as per product instructions. Relative luminescence was measured.

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In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.15 nM
Low MUC1 expression (MUC1+);High EGFR expression (EGFR+++)
Method Description
A total of 625 cells (MDA-MB-468) in a volume of 25 uL were seeded in a 384-well flat bottom white polystyrene plate the day before the actual assay started. ADC and free drugs were formulated at 2x starting concentration in cell culture medium and filtered through 0.22um cellulose acetate filtered 2 ml centrifuge tubes. Filter sterilized samples were serial diluted (1:3) under sterile conditions and 25 uL of each dilution was added onto cells in triplicates. Plates were cultured at 37 °C in a C02 incubator for 120 hours. For cell viability measurement, 30 uL of Cell Titer-Glo@ reagent (PromegaT M Corp, Madison, WI) was added into each well, and plates processed as per product instructions. Relative luminescence was measured.

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In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.17 nM
Low MUC1 expression (MUC1+);Moderate EGFR expression (EGFR++)
Method Description
A total of 625 cells (NCI-H292) were plated in 90 ul cell culture medium per well of a 96-well black/clear flat bottom TC-treated imaging microplate and cultured overnight. A ten-fold starting concentration of ADCs, a respective serial dilution (1:4) were prepared in cell culture medium briefly before use. Wells were supplied with 10 ul ADC or compound solution. Treatment was performed in technical triplicates. The plates were subsequently incubated for 144h. For subsequent cell viability measurement, 100 ul Cell Titer-Glo reagent was pipetted in each well, and plates were further processed according the manufacturer's instructions.

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In Vitro Model Lung mucoepidermoid carcinoma NCI-H292 cells CVCL_0455
Anti-MUC1 ADC [Investigative]
 ADC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
0.65 nM
High MUC1 expression (MUC1 +++);Low EGFR expression (EGFR+)
Method Description
A total of 625 cells (WISH) in a volume of 25 uL were seeded in a 384-well flat bottom white polystyrene plate the day before the actual assay started. ADC and free drugs were formulated at 2x starting concentration in cell culture medium and filtered through 0.22um cellulose acetate filtered 2 ml centrifuge tubes. Filter sterilized samples were serial diluted (1:3) under sterile conditions and 25 uL of each dilution was added onto cells in triplicates. Plates were cultured at 37 °C in a C02 incubator for 120 hours. For cell viability measurement, 30 uL of Cell Titer-Glo@ reagent (PromegaT M Corp, Madison, WI) was added into each well, and plates processed as per product instructions. Relative luminescence was measured.

   Click to Show/Hide
In Vitro Model Endocervical adenocarcinoma WISH cells CVCL_1909
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
2.7 nM
Low MUC1 expression (MUC1+);High EGFR expression (EGFR+++)
Method Description
A total of 625 cells (MDA-MB-468) in a volume of 25 uL were seeded in a 384-well flat bottom white polystyrene plate the day before the actual assay started. ADC and free drugs were formulated at 2x starting concentration in cell culture medium and filtered through 0.22um cellulose acetate filtered 2 ml centrifuge tubes. Filter sterilized samples were serial diluted (1:3) under sterile conditions and 25 uL of each dilution was added onto cells in triplicates. Plates were cultured at 37 °C in a C02 incubator for 120 hours. For cell viability measurement, 30 uL of Cell Titer-Glo@ reagent (PromegaT M Corp, Madison, WI) was added into each well, and plates processed as per product instructions. Relative luminescence was measured.

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In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
3.6 nM
Moderate MUC1 expression (MUC1++);Low EGFR expression (EGFR+)
Method Description
A total of 625 cells (OVCAR-3) in a volume of 25 uL were seeded in a 384-well flat bottom white polystyrene plate the day before the actual assay started. ADC and free drugs were formulated at 2x starting concentration in cell culture medium and filtered through 0.22um cellulose acetate filtered 2 ml centrifuge tubes. Filter sterilized samples were serial diluted (1:3) under sterile conditions and 25 uL of each dilution was added onto cells in triplicates. Plates were cultured at 37 °C in a C02 incubator for 120 hours. For cell viability measurement, 30 uL of Cell Titer-Glo@ reagent (PromegaT M Corp, Madison, WI) was added into each well, and plates processed as per product instructions. Relative luminescence was measured.

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In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
4.5 nM
Low MUC1 expression (MUC1+);High EGFR expression (EGFR+++)
Method Description
A total of 625 cells (NCI-H292) were plated in 90 ul cell culture medium per well of a 96-well black/clear flat bottom TC-treated imaging microplate and cultured overnight. A ten-fold starting concentration of ADCs, a respective serial dilution (1:4) were prepared in cell culture medium briefly before use. Wells were supplied with 10 ul ADC or compound solution. Treatment was performed in technical triplicates. The plates were subsequently incubated for 144h. For subsequent cell viability measurement, 100 ul Cell Titer-Glo reagent was pipetted in each well, and plates were further processed according the manufacturer's instructions.

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In Vitro Model Lung adenocarcinoma HCC827 cells CVCL_2063
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
20 nM
Low MUC1 expression (MUC1+);Moderate EGFR expression (EGFR++)
Method Description
A total of 625 cells (NCI-H292) were plated in 90 ul cell culture medium per well of a 96-well black/clear flat bottom TC-treated imaging microplate and cultured overnight. A ten-fold starting concentration of ADCs, a respective serial dilution (1:4) were prepared in cell culture medium briefly before use. Wells were supplied with 10 ul ADC or compound solution. Treatment was performed in technical triplicates. The plates were subsequently incubated for 144h. For subsequent cell viability measurement, 100 ul Cell Titer-Glo reagent was pipetted in each well, and plates were further processed according the manufacturer's instructions.

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In Vitro Model Lung mucoepidermoid carcinoma NCI-H292 cells CVCL_0455
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
310 nM
Low MUC1 expression (MUC1+);Low EGFR expression (EGFR+)
Method Description
A total of 625 cells (NCI-H292) were plated in 90 ul cell culture medium per well of a 96-well black/clear flat bottom TC-treated imaging microplate and cultured overnight. A ten-fold starting concentration of ADCs, a respective serial dilution (1:4) were prepared in cell culture medium briefly before use. Wells were supplied with 10 ul ADC or compound solution. Treatment was performed in technical triplicates. The plates were subsequently incubated for 144h. For subsequent cell viability measurement, 100 ul Cell Titer-Glo reagent was pipetted in each well, and plates were further processed according the manufacturer's instructions.

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In Vitro Model Lung adenocarcinoma NCI-H1975 cells CVCL_1511
References
Ref 1 Bispecific antibody-drug conjugates targeting EGFR and MUC1 and uses thereof