Payload Information
General Information of This Payload
| Payload ID | PAY0LLEOJ |
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|---|---|---|---|---|---|---|
| Name | MZ1 |
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| Synonyms |
MZ1
Click to Show/Hide
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| Target | Bromodomain-containing protein 4 (BRD4) | |||||
| Formula | C49H60ClN9O8S2 |
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| Isosmiles | CC1=C(C)SC2=C1C(C3=CC=C(Cl)C=C3)=N[C@@H](CC(NCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N4C[C@H](O)C[C@H]4C(NCC5=CC=C(C6=C(C)N=CS6)C=C5)=O)=O)=O)=O)C7=NN=C(C)N72 |
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| PubChem CID | ||||||
| InChI |
InChI=1S/C49H60ClN9O8S2/c1-28-30(3)69-48-41(28)42(33-12-14-35(50)15-13-33)54-37(45-57-56-31(4)59(45)48)23-39(61)51-16-17-65-18-19-66-20-21-67-26-40(62)55-44(49(5,6)7)47(64)58-25-36(60)22-38(58)46(63)52-24-32-8-10-34(11-9-32)43-29(2)53-27-68-43/h8-15,27,36-38,44,60H,16-26H2,1-7H3,(H,51,61)(H,52,63)(H,55,62)/t36-,37+,38+,44-/m1/s1
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| InChIKey |
PTAMRJLIOCHJMQ-PYNGZGNASA-N
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| Pharmaceutical Properties | Molecule Weight |
1002.661 |
Polar area |
211.49 |
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Complexity |
2549.264601 |
xlogp Value |
5.59668 |
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Heavy Count |
69 |
Rot Bonds |
20 |
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Hbond acc |
15 |
Hbond Donor |
4 |
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The activity data of This Payload
| Standard Type | Value | Units | Cell line | Disease Model | Cell line ID | Reference |
|---|---|---|---|---|---|---|
| Cell-based Growth Rate | -19 | % |
U2OS cells
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Osteosarcoma
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| Cell-based Growth Rate | -26 | % |
Fibroblast cells
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Multiple myeloma, Plasma cell myeloma
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Undisclosed | |
| Cell-based Growth Rate | 1 | % |
HEK-293T cells
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Normal
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| Cell-based Growth Rate | 16 | % |
HEK-293T cells
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Normal
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| Cell-based Growth Rate | 23 | % |
Fibroblast cells
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Multiple myeloma, Plasma cell myeloma
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Undisclosed | |
| Cellular activity | 25 | % |
HEK293 cells
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Normal
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| Cell-based Growth Rate | 31 | % |
U2OS cells
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Osteosarcoma
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| Cellular activity | 48 | % |
HEK293 cells
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Normal
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| Tumor Growth Inhibition (TGI) | 59.8 | % |
MCF-7 cells
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Invasive breast carcinoma of no special type
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| Cellular activity | 68 | % | Undisclosed | Undisclosed | Undisclosed | |
| Cellular activity | 82 | % | Undisclosed | Undisclosed | Undisclosed | |
| Cellular activity | 84 | % |
MV4-11 cells
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Childhood acute monocytic leukemia
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| Cellular activity | 90 | % |
HeLa cells
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Human papillomavirus-related endocervical adenocarcinoma
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| Cellular activity | 94 | % |
MOLT-4 cells
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Adult T acute lymphoblastic leukemia
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| Cellular activity | 96 | % |
MV4-11 cells
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Childhood acute monocytic leukemia
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| Half Maximal Inhibitory Concentration (IC50) | 1.5 | nM |
HL-60 cells
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Acute myeloblastic leukemia with maturation, Adult acute myeloid leukemia with maturation
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| Half Maximal Inhibitory Concentration (IC50) | 1.5 | nM |
Cancer cells
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Multiple myeloma, Plasma cell myeloma
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Undisclosed | |
| Half Maximal Degradation Concentration (DC50) | 10 | nM |
HeLa cells
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Human papillomavirus-related endocervical adenocarcinoma
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| Half Maximal Degradation Concentration (DC50) | <100 | nM |
HeLa cells
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Human papillomavirus-related endocervical adenocarcinoma
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| Half Maximal Degradation Concentration (DC50) | <100 | nM |
HeLa cells
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Human papillomavirus-related endocervical adenocarcinoma
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| Half Maximal Degradation Concentration (DC50) | <100 | nM |
HeLa cells
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Human papillomavirus-related endocervical adenocarcinoma
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| Half Maximal Degradation Concentration (DC50) | <100 | nM | Undisclosed | Undisclosed | Undisclosed | |
| Half Maximal Inhibitory Concentration (IC50) | 11.3 | nM |
MV4-11 cells
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Childhood acute monocytic leukemia
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| Half Maximal Effective Concentration (EC50) | 125.89 | nM |
MV4-11 cells
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Childhood acute monocytic leukemia
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| Half Maximal Degradation Concentration (DC50) | 13 | nM |
MCF-7 cells
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Invasive breast carcinoma of no special type
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| Half Maximal Degradation Concentration (DC50) | 143 | nM |
HEK293 cells
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Normal
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| Half Maximal Effective Concentration (EC50) | 150 | nM |
22Rv1 cells
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Prostate carcinoma
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| Half Maximal Degradation Concentration (DC50) | 2 | nM |
Cancer cells
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Multiple myeloma, Plasma cell myeloma
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Undisclosed | |
| Half Maximal Effective Concentration (EC50) | 218.78 | nM |
HL-60 cells
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Acute myeloblastic leukemia with maturation, Adult acute myeloid leukemia with maturation
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| Half Maximal Inhibitory Concentration (IC50) | ~22.92 | nM |
Vero C1008 cells
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Normal
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| Half Maximal Degradation Concentration (DC50) | 25 | nM |
HEK293 cells
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Normal
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| Half Maximal Effective Concentration (EC50) | 26.92 | nM |
MV4-11 cells
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Childhood acute monocytic leukemia
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| Half Maximal Effective Concentration (EC50) | 50.12 | nM |
MV4-11 cells
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Childhood acute monocytic leukemia
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| Half Maximal Effective Concentration (EC50) | 501.19 | nM |
Cancer cells
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Multiple myeloma, Plasma cell myeloma
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Undisclosed | |
| Half Maximal Inhibitory Concentration (IC50) | 623 | nM | Undisclosed | Undisclosed | Undisclosed | |
| Half Maximal Inhibitory Concentration (IC50) | 639 | nM | Undisclosed | Undisclosed | Undisclosed | |
| Half Maximal Inhibitory Concentration (IC50) | 660 | nM | Undisclosed | Undisclosed | Undisclosed | |
| Half Maximal Inhibitory Concentration (IC50) | 708 | nM | Undisclosed | Undisclosed | Undisclosed | |
| Half Maximal Inhibitory Concentration (IC50) | 722 | nM | Undisclosed | Undisclosed | Undisclosed | |
| Half Maximal Inhibitory Concentration (IC50) | 798 | nM | Undisclosed | Undisclosed | Undisclosed | |
| Half Maximal Inhibitory Concentration (IC50) | 882 | nM | Undisclosed | Undisclosed | Undisclosed | |
| Half Maximal Degradation Concentration (DC50) | 9232 | nM |
HEK293 cells
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Normal
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| Half Maximal Degradation Concentration (DC50) | 0.008 | uM |
NCI-H661 cells
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Lung large cell carcinoma
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| Half Maximal Degradation Concentration (DC50) | 0.013 | uM |
HEK293 cells
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Normal
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| Half Maximal Degradation Concentration (DC50) | 0.017 | uM |
HEK293 cells
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Normal
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Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
ROR1 DAC (KLY) [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
57.86 nM
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| Method Description |
Five thousand tumor cells were seeded in 96-well plates and cultured overnight. ROR1 mAb, ROR1 DAC, and MZ1 were serially diluted and added to the plates. After four days of incubation, cell viability was assessed using a Cell Counting Kit-8 (CCK-8, Dojindo, Kumamoto, Japan).
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Western blotting analysis
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Degradation Concentration (DC50) |
26.22 nM
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| Method Description |
After drug treatment in a 12-well plate, the wells were aspirated and washed with PBS. Cells were lysed with 100 uL cold Western and IP lysis buffer containing a 2% inhibitor cocktail (Beyotime, Shanghai, China) for 10 min on ice. After centrifugation (12,000 g, 10 min, 4 °C), the supernatants were collected and quantified with bicinchoninic acid assay (BCA) assay kit (Beyotime, Shanghai, China). 20-30 ug total protein was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred onto the polyvinylidene fluoride (PVDF) membrane. The membrane was subsequently washed with PBST (0.1% Tween-20) and incubated with 5% skim milk at room temperature for 2 h, BRD4 (E2A7X) rabbit mAb (Cell Signaling Technology, Danvers, MA, USA) or beta-actin antibody (Affinity, Liyang, China) at 4 °C overnight, anti-rabbit IgG-HRP-linked antibody (Cell Signaling Technology, Danvers, MA, USA) at room temperature for 1 h. Finally, the bands were detected using ECL reagent (NCM biotech, Suzhou, China) by Tanon-4600 imaging system (Shanghai, China).
Click to Show/Hide
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ROR1 DAC (KV) [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
74.64 nM
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| Method Description |
Five thousand tumor cells were seeded in 96-well plates and cultured overnight. ROR1 mAb, ROR1 DAC, and MZ1 were serially diluted and added to the plates. After four days of incubation, cell viability was assessed using a Cell Counting Kit-8 (CCK-8, Dojindo, Kumamoto, Japan).
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Western blotting analysis
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Degradation Concentration (DC50) |
54.28 nM
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| Method Description |
After drug treatment in a 12-well plate, the wells were aspirated and washed with PBS. Cells were lysed with 100 uL cold Western and IP lysis buffer containing a 2% inhibitor cocktail (Beyotime, Shanghai, China) for 10 min on ice. After centrifugation (12,000 g, 10 min, 4 °C), the supernatants were collected and quantified with bicinchoninic acid assay (BCA) assay kit (Beyotime, Shanghai, China). 20-30 ug total protein was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred onto the polyvinylidene fluoride (PVDF) membrane. The membrane was subsequently washed with PBST (0.1% Tween-20) and incubated with 5% skim milk at room temperature for 2 h, BRD4 (E2A7X) rabbit mAb (Cell Signaling Technology, Danvers, MA, USA) or beta-actin antibody (Affinity, Liyang, China) at 4 °C overnight, anti-rabbit IgG-HRP-linked antibody (Cell Signaling Technology, Danvers, MA, USA) at room temperature for 1 h. Finally, the bands were detected using ECL reagent (NCM biotech, Suzhou, China) by Tanon-4600 imaging system (Shanghai, China).
Click to Show/Hide
|
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ROR1 DAC (LY) [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
76.71 nM
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| Method Description |
Five thousand tumor cells were seeded in 96-well plates and cultured overnight. ROR1 mAb, ROR1 DAC, and MZ1 were serially diluted and added to the plates. After four days of incubation, cell viability was assessed using a Cell Counting Kit-8 (CCK-8, Dojindo, Kumamoto, Japan).
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Western blotting analysis
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Degradation Concentration (DC50) |
46.58 nM
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| Method Description |
After drug treatment in a 12-well plate, the wells were aspirated and washed with PBS. Cells were lysed with 100 uL cold Western and IP lysis buffer containing a 2% inhibitor cocktail (Beyotime, Shanghai, China) for 10 min on ice. After centrifugation (12,000 g, 10 min, 4 °C), the supernatants were collected and quantified with bicinchoninic acid assay (BCA) assay kit (Beyotime, Shanghai, China). 20-30 ug total protein was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred onto the polyvinylidene fluoride (PVDF) membrane. The membrane was subsequently washed with PBST (0.1% Tween-20) and incubated with 5% skim milk at room temperature for 2 h, BRD4 (E2A7X) rabbit mAb (Cell Signaling Technology, Danvers, MA, USA) or beta-actin antibody (Affinity, Liyang, China) at 4 °C overnight, anti-rabbit IgG-HRP-linked antibody (Cell Signaling Technology, Danvers, MA, USA) at room temperature for 1 h. Finally, the bands were detected using ECL reagent (NCM biotech, Suzhou, China) by Tanon-4600 imaging system (Shanghai, China).
Click to Show/Hide
|
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ROR1 DAC (K149C) [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
128 nM
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| Method Description |
Five thousand tumor cells were seeded in 96-well plates and cultured overnight. ROR1 mAb, ROR1 DAC, and MZ1 were serially diluted and added to the plates. After four days of incubation, cell viability was assessed using a Cell Counting Kit-8 (CCK-8, Dojindo, Kumamoto, Japan).
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Western blotting analysis
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Degradation Concentration (DC50) |
237.8 nM
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| Method Description |
After drug treatment in a 12-well plate, the wells were aspirated and washed with PBS. Cells were lysed with 100 uL cold Western and IP lysis buffer containing a 2% inhibitor cocktail (Beyotime, Shanghai, China) for 10 min on ice. After centrifugation (12,000 g, 10 min, 4 °C), the supernatants were collected and quantified with bicinchoninic acid assay (BCA) assay kit (Beyotime, Shanghai, China). 20-30 ug total protein was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred onto the polyvinylidene fluoride (PVDF) membrane. The membrane was subsequently washed with PBST (0.1% Tween-20) and incubated with 5% skim milk at room temperature for 2 h, BRD4 (E2A7X) rabbit mAb (Cell Signaling Technology, Danvers, MA, USA) or beta-actin antibody (Affinity, Liyang, China) at 4 °C overnight, anti-rabbit IgG-HRP-linked antibody (Cell Signaling Technology, Danvers, MA, USA) at room temperature for 1 h. Finally, the bands were detected using ECL reagent (NCM biotech, Suzhou, China) by Tanon-4600 imaging system (Shanghai, China).
Click to Show/Hide
|
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References