Linker Information
General Information of This Linker
| Linker ID |
LIN0XBIRK
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| Linker Name |
AU2023279443A1, Example 5, 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 |
C107H175N19O46P2
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| Isosmiles |
CC(C)[C@@H](C(N[C@@H](CCCNC(N)=O)C(NC1=CC=C(C=C1)COP(O)(O)=O)=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/C107H175N19O46P2/c1-74(2)95(102(141)121-80(7-5-25-112-106(108)145)97(136)115-78-13-9-76(72-127)10-14-78)123-99(138)84(69-91(132)117-82-19-35-170-104(82)143)119-89(130)22-33-154-43-51-162-59-63-166-55-47-158-39-29-125(31-41-160-49-57-168-65-67-169-66-62-164-53-45-156-37-27-110-87(128)21-32-153-42-50-161-58-61-165-54-46-157-38-28-111-101(140)86(126-93(134)17-18-94(126)135)71-114-88(129)24-68-173(147,148)149)30-40-159-48-56-167-64-60-163-52-44-155-34-23-90(131)120-85(70-92(133)118-83-20-36-171-105(83)144)100(139)124-96(75(3)4)103(142)122-81(8-6-26-113-107(109)146)98(137)116-79-15-11-77(12-16-79)73-172-174(150,151)152/h9-18,74-75,80-86,95-96,127H,5-8,19-73H2,1-4H3,(H,110,128)(H,111,140)(H,114,129)(H,115,136)(H,116,137)(H,117,132)(H,118,133)(H,119,130)(H,120,131)(H,121,141)(H,122,142)(H,123,138)(H,124,139)(H3,108,112,145)(H3,109,113,146)(H2,147,148,149)(H2,150,151,152)/t80-,81-,82-,83-,84-,85-,86-,95-,96-/m0/s1
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| InChIKey |
SIIGLPSUCFKSJB-MULHCVPBSA-N
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| Pharmaceutical Properties |
Molecule Weight
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2525.612
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Polar area
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883.19
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Complexity
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.
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xlogp Value
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-5.9087
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Heavy Count
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174
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Rot Bonds
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104
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Hbond acc
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43
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Hbond Donor
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22
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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 5 [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.
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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 (%) |
101%
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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 | ||