Linker Information
General Information of This Linker
| Linker ID |
LIN0WGHPO
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| Linker Name |
AB2 self-immolative dendritic scaffold
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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 |
C56H73N13O21
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| Isosmiles |
CC(C)[C@H](NC(CCCNC(CCN1C(C=CC1=O)=O)=O)=O)C(N[C@H](C(NC2=CC=C(COC(C(CO)=CC(C(NCC(N=N3)=CN3[C@@H](CCC(N[C@H](C(O)=O)CCC(O)=O)=O)C(N[C@H](C(O)=O)CCC(O)=O)=O)=O)=C4)=C4CO)C=C2)=O)CCCNC(N)=O)=O
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| InChI |
InChI=1S/C56H73N13O21/c1-30(2)48(65-42(73)6-4-20-58-41(72)19-22-68-44(75)15-16-45(68)76)53(84)63-37(5-3-21-59-56(57)89)51(82)61-35-9-7-31(8-10-35)29-90-49-33(27-70)23-32(24-34(49)28-71)50(81)60-25-36-26-69(67-66-36)40(52(83)64-39(55(87)88)12-18-47(79)80)13-14-43(74)62-38(54(85)86)11-17-46(77)78/h7-10,15-16,23-24,26,30,37-40,48,70-71H,3-6,11-14,17-22,25,27-29H2,1-2H3,(H,58,72)(H,60,81)(H,61,82)(H,62,74)(H,63,84)(H,64,83)(H,65,73)(H,77,78)(H,79,80)(H,85,86)(H,87,88)(H3,57,59,89)/t37-,38-,39-,40-,48-/m0/s1
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| InChIKey |
GQVVQODNYGSVFB-XMGYJUAHSA-N
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| Pharmaceutical Properties |
Molecule Weight
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1264.27
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Polar area
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525.8
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Complexity
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2987.724439
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xlogp Value
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-1.8145
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Heavy Count
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90
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Rot Bonds
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40
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Hbond acc
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20
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Hbond Donor
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15
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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
Tras-Exa [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) |
0.6 nM
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High HER2 expression (HER2 +++) | ||
| Method Description |
HCC-1954, JIMT-1 and MDA-MB-468 cells were plated in 24-well culture plates (5000, 5000 and 10,000 cells/well, respectively) and incubated for 24 h. Cells were then exposed to serial dilutions of trastuzumab, free exatecan, or Tras-Exa (DAR4) ADC. Cell viability was evaluated following 6 days of incubation using MTT (3 ug/mL, Sigma). MTT absorbance was measured at 570 nm using SpectraMax M5e multi-detection reader.
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| In Vitro Model | Breast ductal carcinoma | HCC-1954 cells | CVCL_1259 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
40 nM
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Positive HER2 expression (HER2+++/++) | ||
| Method Description |
HCC-1954, JIMT-1 and MDA-MB-468 cells were plated in 24-well culture plates (5000, 5000 and 10,000 cells/well, respectively) and incubated for 24 h. Cells were then exposed to serial dilutions of trastuzumab, free exatecan, or Tras-Exa (DAR4) ADC. Cell viability was evaluated following 6 days of incubation using MTT (3 ug/mL, Sigma). MTT absorbance was measured at 570 nm using SpectraMax M5e multi-detection reader.
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| In Vitro Model | Breast ductal carcinoma | JIMT-1 cells | CVCL_2077 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
50 nM
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Low HER2 expression (HER2+) | ||
| Method Description |
HCC-1954, JIMT-1 and MDA-MB-468 cells were plated in 24-well culture plates (5000, 5000 and 10,000 cells/well, respectively) and incubated for 24 h. Cells were then exposed to serial dilutions of trastuzumab, free exatecan, or Tras-Exa (DAR4) ADC. Cell viability was evaluated following 6 days of incubation using MTT (3 ug/mL, Sigma). MTT absorbance was measured at 570 nm using SpectraMax M5e multi-detection reader.
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| In Vitro Model | Breast adenocarcinoma | MDA-MB-468 cells | CVCL_0419 | ||
References