Linker Information
General Information of This Linker
| Linker ID |
LIN0QQSLC
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| Linker Name |
AU2023279443A1, Example 3, 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 |
C107H174N19O43P
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| Isosmiles |
CC(C)[C@@H](C(N[C@@H](CCCNC(N)=O)C(NC1=CC=C(C=C1)CO)=O)=O)NC([C@H](CC(N[C@H]2CCOC2=O)=O)NC(CCOCCOCCOCCOCCN(CCOCCOCCOCCOCCOCCNC(CCOCCOCCOCCOCCNC([C@H](CNC(CCP(O)(O)=O)=O)N3C(C=CC3=O)=O)=O)=O)CCOCCOCCOCCOCCC(N[C@H](C(N[C@@H](C(C)C)C(N[C@H](C(NC4=CC=C(C=C4)CO)=O)CCCNC(N)=O)=O)=O)CC(N[C@H]5CCOC5=O)=O)=O)=O)=O
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| InChI |
InChI=1S/C107H174N19O43P/c1-74(2)95(102(142)121-80(7-5-25-112-106(108)146)97(137)115-78-13-9-76(72-127)10-14-78)123-99(139)84(69-91(133)117-82-19-35-168-104(82)144)119-89(131)22-33-152-43-51-160-59-63-164-55-47-156-39-29-125(31-41-158-49-57-166-65-67-167-66-62-162-53-45-154-37-27-110-87(129)21-32-151-42-50-159-58-61-163-54-46-155-38-28-111-101(141)86(126-93(135)17-18-94(126)136)71-114-88(130)24-68-170(148,149)150)30-40-157-48-56-165-64-60-161-52-44-153-34-23-90(132)120-85(70-92(134)118-83-20-36-169-105(83)145)100(140)124-96(75(3)4)103(143)122-81(8-6-26-113-107(109)147)98(138)116-79-15-11-77(73-128)12-16-79/h9-18,74-75,80-86,95-96,127-128H,5-8,19-73H2,1-4H3,(H,110,129)(H,111,141)(H,114,130)(H,115,137)(H,116,138)(H,117,133)(H,118,134)(H,119,131)(H,120,132)(H,121,142)(H,122,143)(H,123,139)(H,124,140)(H3,108,112,146)(H3,109,113,147)(H2,148,149,150)/t80-,81-,82-,83-,84-,85-,86-,95-,96-/m0/s1
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| InChIKey |
MNGJEWVGSMDUSR-MULHCVPBSA-N
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| Pharmaceutical Properties |
Molecule Weight
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2445.633
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Polar area
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836.66
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Complexity
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.
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xlogp Value
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-6.0257
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Heavy Count
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170
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Rot Bonds
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102
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Hbond acc
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42
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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 2 [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) | > 100% | 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.
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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.
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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 (%) |
102%
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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 | ||