Linker Information
General Information of This Linker
| Linker ID |
LIN0ZYTUY
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| Linker Name |
LPETGGG-PEG3-Azide BCN-AVC
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| Linker Type |
Cathepsin-cleavable linker
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| Antibody-Linker Relation |
Cleavable
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| Structure |
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| Formula |
C64H105N17O23
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| Isosmiles |
CC(C[C@H](N)C(N(CCC1)[C@@H]1C(N[C@H](C(N[C@@H]([C@H](O)C)C(NCC(NCC(NCC(NCCOCCOCCOCCN2N=NC3=C2CCC4C([C@@H]4COC(N[C@@H](C)C(NC(C(N[C@H](CCCNC(N)=O)C(N[C@H](CCC(O)=O)C(O)=O)=O)=O)C(C)C)=O)=O)CC3)=O)=O)=O)=O)=O)CCC(O)=O)=O)=O)C
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| InChI |
InChI=1S/C64H105N17O23/c1-34(2)29-41(65)61(96)80-21-8-10-47(80)58(93)73-44(14-17-51(86)87)57(92)77-54(37(6)82)59(94)71-32-50(85)70-31-49(84)69-30-48(83)67-20-23-101-25-27-103-28-26-102-24-22-81-46-16-12-39-38(11-13-42(46)78-79-81)40(39)33-104-64(100)72-36(5)55(90)76-53(35(3)4)60(95)74-43(9-7-19-68-63(66)99)56(91)75-45(62(97)98)15-18-52(88)89/h34-41,43-45,47,53-54,82H,7-33,65H2,1-6H3,(H,67,83)(H,69,84)(H,70,85)(H,71,94)(H,72,100)(H,73,93)(H,74,95)(H,75,91)(H,76,90)(H,77,92)(H,86,87)(H,88,89)(H,97,98)(H3,66,68,99)/t36-,37+,38?,39?,40-,41-,43+,44-,45+,47-,53?,54-/m0/s1
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| InChIKey |
MGPXZXAERYONTA-UKIIMEQJSA-N
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| Pharmaceutical Properties |
Molecule Weight
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1480.64
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Polar area
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592.21
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Complexity
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2959.873419
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xlogp Value
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-5.2637
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Heavy Count
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104
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Rot Bonds
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48
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Hbond acc
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24
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Hbond Donor
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17
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Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Fab-SN38 [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) |
2.23۪.14 nM
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High HER2 expression (HER2 +++) | ||
| Method Description |
The cytotoxicity of Fab-SN38 was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Cells (MDA-MB-231, Calu-3, NCI-N87 and SK-OV-3 cells) were seeded into clear-bottom 96-well plates (~3000 cells per well). After overnight culture, the medium was removed and the fresh medium containing SN38, Glu (SN38)-OH, Glu-SN38, trastuzumab, the Fab protein or the Fab-SN38 conjugate was added and incubated for 72 h at 37 °C in a CO2 incubator. Cell viability was measured using the CCK-8 reagent according to the protocol. Briefly, 15 uL of CCK-8 solution was added to the culture media. Two hours after incubation at 37 °C, the absorbance at a wavelength of 450 nm was measured by a microplate reader (TECAN, Switzerland) and then the IC50 value was profiled using the Graphpad Prism 8 software.
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| In Vitro Model | Ovarian serous cystadenocarcinoma | SK-OV-3 cells | CVCL_0532 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
3.5۪.16 nM
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High HER2 expression (HER2 +++) | ||
| Method Description |
The cytotoxicity of Fab-SN38 was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Cells (MDA-MB-231, Calu-3, NCI-N87 and SK-OV-3 cells) were seeded into clear-bottom 96-well plates (~3000 cells per well). After overnight culture, the medium was removed and the fresh medium containing SN38, Glu (SN38)-OH, Glu-SN38, trastuzumab, the Fab protein or the Fab-SN38 conjugate was added and incubated for 72 h at 37 °C in a CO2 incubator. Cell viability was measured using the CCK-8 reagent according to the protocol. Briefly, 15 uL of CCK-8 solution was added to the culture media. Two hours after incubation at 37 °C, the absorbance at a wavelength of 450 nm was measured by a microplate reader (TECAN, Switzerland) and then the IC50 value was profiled using the Graphpad Prism 8 software.
Click to Show/Hide
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| In Vitro Model | Lung adenocarcinoma | Calu-3 cells | CVCL_0609 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
8.47۪.29 nM
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Positive HER2 expression (HER2+++/++) | ||
| Method Description |
The cytotoxicity of Fab-SN38 was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Cells (MDA-MB-231, Calu-3, NCI-N87 and SK-OV-3 cells) were seeded into clear-bottom 96-well plates (~3000 cells per well). After overnight culture, the medium was removed and the fresh medium containing SN38, Glu (SN38)-OH, Glu-SN38, trastuzumab, the Fab protein or the Fab-SN38 conjugate was added and incubated for 72 h at 37 °C in a CO2 incubator. Cell viability was measured using the CCK-8 reagent according to the protocol. Briefly, 15 uL of CCK-8 solution was added to the culture media. Two hours after incubation at 37 °C, the absorbance at a wavelength of 450 nm was measured by a microplate reader (TECAN, Switzerland) and then the IC50 value was profiled using the Graphpad Prism 8 software.
Click to Show/Hide
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| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | > 1000 nM | Negative HER2 expression (HER2-) | ||
| Method Description |
The cytotoxicity of Fab-SN38 was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Cells (MDA-MB-231, Calu-3, NCI-N87 and SK-OV-3 cells) were seeded into clear-bottom 96-well plates (~3000 cells per well). After overnight culture, the medium was removed and the fresh medium containing SN38, Glu (SN38)-OH, Glu-SN38, trastuzumab, the Fab protein or the Fab-SN38 conjugate was added and incubated for 72 h at 37 °C in a CO2 incubator. Cell viability was measured using the CCK-8 reagent according to the protocol. Briefly, 15 uL of CCK-8 solution was added to the culture media. Two hours after incubation at 37 °C, the absorbance at a wavelength of 450 nm was measured by a microplate reader (TECAN, Switzerland) and then the IC50 value was profiled using the Graphpad Prism 8 software.
Click to Show/Hide
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| In Vitro Model | Breast adenocarcinoma | MDA-MB-231 cells | CVCL_0062 | ||