Linker Information
General Information of This Linker
| Linker ID |
LIN0RSBPH
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|---|---|---|---|---|---|---|
| Linker Name |
AU2023279443A1, Example 4, Linker
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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 |
C87H134N18O37P2
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| Isosmiles |
CC([C@H](NC([C@@H](NC(CCOCCOCCN(CCOCCOCCC(N[C@@H](CC(N[C@H]1CCOC1=O)=O)C(N[C@H](C(N[C@@H](CCCNC(N)=O)C(NC2=CC=C(CO)C=C2)=O)=O)C(C)C)=O)=O)C(CCOCCOCCOCCOCCNC([C@@H](N3C(C=CC3=O)=O)CNC(CCP(O)(O)=O)=O)=O)=O)=O)CC(N[C@H]4CCOC4=O)=O)=O)C(N[C@@H](CCCNC(N)=O)C(NC5=CC=C(C=C5)COP(O)(O)=O)=O)=O)C
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| InChI |
InChI=1S/C87H134N18O37P2/c1-54(2)75(82(120)100-60(7-5-25-91-86(88)124)77(115)94-58-13-9-56(52-106)10-14-58)102-79(117)64(49-70(110)96-62-19-33-140-84(62)122)98-68(108)21-30-132-38-42-136-36-28-104(72(112)23-32-134-40-44-138-46-47-139-45-41-135-35-27-90-81(119)66(105-73(113)17-18-74(105)114)51-93-67(107)24-48-143(126,127)128)29-37-137-43-39-133-31-22-69(109)99-65(50-71(111)97-63-20-34-141-85(63)123)80(118)103-76(55(3)4)83(121)101-61(8-6-26-92-87(89)125)78(116)95-59-15-11-57(12-16-59)53-142-144(129,130)131/h9-18,54-55,60-66,75-76,106H,5-8,19-53H2,1-4H3,(H,90,119)(H,93,107)(H,94,115)(H,95,116)(H,96,110)(H,97,111)(H,98,108)(H,99,109)(H,100,120)(H,101,121)(H,102,117)(H,103,118)(H3,88,91,124)(H3,89,92,125)(H2,126,127,128)(H2,129,130,131)/t60-,61-,62-,63-,64-,65-,66-,75-,76-/m0/s1
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| InChIKey |
FRZHYTCJXONTOS-FCMBBISSSA-N
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| Pharmaceutical Properties |
Molecule Weight
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2086.066
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Polar area
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788.09
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Complexity
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.
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xlogp Value
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-5.6477
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Heavy Count
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144
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Rot Bonds
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74
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Hbond acc
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33
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Hbond Donor
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21
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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
aU2023279443A1 Example 3 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 50% | Positive HER2 expression (HER2+++/++) | ||
| Method Description |
A mixed solvent of PBS and and Matrigel was used to prepare a cell suspension of 5.0x107 cells / mL. The prepared cell suspension was subcutaneously injected to the right flank region of female BALB/c-nu/nu mice at 0.1 mL per mouse. Individuals having a tumor volume within a range of 50 to 500 mm 3 were selected. test compound at a concentration of 1 mg/kg or the solvent alone was intravenously administered. the tumor volume was measured at Day 0 and Day 21.
Click to Show/Hide
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| In Vivo Model | NCI-N87 female BALB/c-nu/nu mice model | ||||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Cell growth inhibition rate (%) | < 10% | Negative HER2 expression (HER2-) | ||
| Method Description |
Growth inhibition test of HER2-negative human breast cancer cell line (MDA-MB-231). The cells were seeded at 1000 cells / 100 pL / well. The cells were cultured at 37 0 C overnight, then the medium was exchanged with new one (95 uL/well), and the cells were treated with a test compound, which was adjusted to 2 ug/mL with PBS , at 5 uL/well (treatment concentration: 100 ng/mL). The cells were cultured for 6 days, then CellTiter-Glo was added thereto at 100 uL/well, and the luminescence amount of each well was measured.
Click to Show/Hide
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| In Vitro Model | Breast adenocarcinoma | MDA-MB-231 cells | CVCL_0062 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Cell growth inhibition rate (%) |
97%
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Positive HER2 expression (HER2+++/++) | ||
| Method Description |
Cell growth inhibition test was carried out on HER2-positive human gastric cancer cell line (NCI-N87), the cells were treated with a test compound or an anti-HER2 antibody (trastuzumab) at a concentration of 100 ng/mL. The cells were cultured for 6 days, then CellTiter-Glo was added and the luminescence amount was measured.
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| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
aU2023279443A1 Example 4 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 50% | Positive HER2 expression (HER2+++/++) | ||
| Method Description |
A mixed solvent of PBS and and Matrigel was used to prepare a cell suspension of 5.0x107 cells / mL. The prepared cell suspension was subcutaneously injected to the right flank region of female BALB/c-nu/nu mice at 0.1 mL per mouse. Individuals having a tumor volume within a range of 50 to 500 mm 3 were selected. test compound at a concentration of 1 mg/kg or the solvent alone was intravenously administered. the tumor volume was measured at Day 0 and Day 21.
Click to Show/Hide
|
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| In Vivo Model | NCI-N87 female BALB/c-nu/nu mice model | ||||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Cell growth inhibition rate (%) | < 10% | Negative HER2 expression (HER2-) | ||
| Method Description |
Growth inhibition test of HER2-negative human breast cancer cell line (MDA-MB-231). The cells were seeded at 1000 cells / 100 pL / well. The cells were cultured at 37 0 C overnight, then the medium was exchanged with new one (95 uL/well), and the cells were treated with a test compound, which was adjusted to 2 ug/mL with PBS , at 5 uL/well (treatment concentration: 100 ng/mL). The cells were cultured for 6 days, then CellTiter-Glo was added thereto at 100 uL/well, and the luminescence amount of each well was measured.
Click to Show/Hide
|
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| In Vitro Model | Breast adenocarcinoma | MDA-MB-231 cells | CVCL_0062 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Cell growth inhibition rate (%) |
100%
|
Positive HER2 expression (HER2+++/++) | ||
| Method Description |
Cell growth inhibition test was carried out on HER2-positive human gastric cancer cell line (NCI-N87), the cells were treated with a test compound or an anti-HER2 antibody (trastuzumab) at a concentration of 100 ng/mL. The cells were cultured for 6 days, then CellTiter-Glo was added and the luminescence amount was measured.
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| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
aU2023279443A1 Example 6 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 50% | Positive HER2 expression (HER2+++/++) | ||
| Method Description |
A mixed solvent of PBS and and Matrigel was used to prepare a cell suspension of 5.0x107 cells / mL. The prepared cell suspension was subcutaneously injected to the right flank region of female BALB/c-nu/nu mice at 0.1 mL per mouse. Individuals having a tumor volume within a range of 50 to 500 mm 3 were selected. test compound at a concentration of 1 mg/kg or the solvent alone was intravenously administered. the tumor volume was measured at Day 0 and Day 21.
Click to Show/Hide
|
||||
| In Vivo Model | NCI-N87 female BALB/c-nu/nu mice model | ||||
aU2023279443A1 Example 7 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Cell growth inhibition rate (%) | < 10% | Negative HER2 expression (HER2-) | ||
| Method Description |
Growth inhibition test of HER2-negative human breast cancer cell line (MDA-MB-231). The cells were seeded at 1000 cells / 100 pL / well. The cells were cultured at 37 0 C overnight, then the medium was exchanged with new one (95 uL/well), and the cells were treated with a test compound, which was adjusted to 2 ug/mL with PBS , at 5 uL/well (treatment concentration: 100 ng/mL). The cells were cultured for 6 days, then CellTiter-Glo was added thereto at 100 uL/well, and the luminescence amount of each well was measured.
Click to Show/Hide
|
||||
| In Vitro Model | Breast adenocarcinoma | MDA-MB-231 cells | CVCL_0062 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Cell growth inhibition rate (%) |
107%
|
Positive HER2 expression (HER2+++/++) | ||
| Method Description |
Cell growth inhibition test was carried out on HER2-positive human gastric cancer cell line (NCI-N87), the cells were treated with a test compound or an anti-HER2 antibody (trastuzumab) at a concentration of 100 ng/mL. The cells were cultured for 6 days, then CellTiter-Glo was added and the luminescence amount was measured.
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| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||