Linker Information
General Information of This Linker
| Linker ID |
LIN00020
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| Linker Name |
Dimethyl disulfide
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| Linker Type |
GSH concentration-sensitive linkers
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| Structure |
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| Formula |
C8H8O2S
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| #Ro5 Violations (Lipinski): 0 | Molecular Weight (mw) | 168.21 | ||||
| Lipid-water partition coefficient (xlogp) | 1.6 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 2 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 3 | |||||
| Rotatable Bond Count (rotbonds) | 2 | |||||
| PubChem CID | ||||||
| Canonical smiles |
C1=CC=C(C(=C1)CC(=O)O)S
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| InChI |
InChI=1S/C8H8O2S/c9-8(10)5-6-3-1-2-4-7(6)11/h1-4,11H,5H2,(H,9,10)
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| InChIKey |
QUCMZSJETXEAMC-UHFFFAOYSA-N
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| IUPAC Name |
2-(2-sulfanylphenyl)acetic acid
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Each Peptide-drug Conjugate Related to This Linker
Full Information of The Activity Data of The PDC(s) Related to This Linker
ER-472 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
5.45%
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| Administration Time | 23days | ||||
| Administration Dosage | 1.25 mg/kg | ||||
| MOA of PDC |
Collectively, our data demonstrate that Cltx within ER-472 acts a cryptic peptide which is metabolized to peptides with C-terminal R-COOH in the tumor microenvironment. These peptides bind to tumor cell NRP1 to increase drug uptake, which consequently boosts the antitumor effect.
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| Description |
At the MTD dose, ER-472 treatment resulted in significant antitumor activity in all 3 models, but at 1/2 MTD no antitumor activity was observed in MIA PaCa-2 or BxPC-3 xenografts. In contrast, a much wider therapeutic window was observed for ER-472 in PC-3 xenografts: tumor regression and several tumor cures were observed at 1/2 MTD and significant antitumor activity was also recorded at the 1/4 MTD dose.
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| In Vivo Model | BxPC-3 xenograft model. | ||||
| Experiment 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
36.70%
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| Administration Time | 30 days | ||||
| Administration Dosage | 1.25 mg/kg | ||||
| MOA of PDC |
Collectively, our data demonstrate that Cltx within ER-472 acts a cryptic peptide which is metabolized to peptides with C-terminal R-COOH in the tumor microenvironment. These peptides bind to tumor cell NRP1 to increase drug uptake, which consequently boosts the antitumor effect.
|
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| Description |
At the MTD dose, ER-472 treatment resulted in significant antitumor activity in all 3 models, but at 1/2 MTD no antitumor activity was observed in MIA PaCa-2 or BxPC-3 xenografts. In contrast, a much wider therapeutic window was observed for ER-472 in PC-3 xenografts: tumor regression and several tumor cures were observed at 1/2 MTD and significant antitumor activity was also recorded at the 1/4 MTD dose.
Click to Show/Hide
|
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| In Vivo Model | MIA PaCa-2 xenograft model. | ||||
| Experiment 3 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
69.23%
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| Administration Time | 38 days | ||||
| Administration Dosage | 0.625 mg/kg | ||||
| MOA of PDC |
Collectively, our data demonstrate that Cltx within ER-472 acts a cryptic peptide which is metabolized to peptides with C-terminal R-COOH in the tumor microenvironment. These peptides bind to tumor cell NRP1 to increase drug uptake, which consequently boosts the antitumor effect.
|
||||
| Description |
At the MTD dose, ER-472 treatment resulted in significant antitumor activity in all 3 models, but at 1/2 MTD no antitumor activity was observed in MIA PaCa-2 or BxPC-3 xenografts. In contrast, a much wider therapeutic window was observed for ER-472 in PC-3 xenografts: tumor regression and several tumor cures were observed at 1/2 MTD and significant antitumor activity was also recorded at the 1/4 MTD dose.
Click to Show/Hide
|
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| In Vivo Model | PC-3 xenograft model. | ||||
| Experiment 4 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
74.54%
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| Administration Time | 23days | ||||
| Administration Dosage | 2.5 mg/kg | ||||
| MOA of PDC |
Collectively, our data demonstrate that Cltx within ER-472 acts a cryptic peptide which is metabolized to peptides with C-terminal R-COOH in the tumor microenvironment. These peptides bind to tumor cell NRP1 to increase drug uptake, which consequently boosts the antitumor effect.
|
||||
| Description |
At the MTD dose, ER-472 treatment resulted in significant antitumor activity in all 3 models, but at 1/2 MTD no antitumor activity was observed in MIA PaCa-2 or BxPC-3 xenografts. In contrast, a much wider therapeutic window was observed for ER-472 in PC-3 xenografts: tumor regression and several tumor cures were observed at 1/2 MTD and significant antitumor activity was also recorded at the 1/4 MTD dose.
Click to Show/Hide
|
||||
| In Vivo Model | BxPC-3 xenograft model. | ||||
| Experiment 5 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
100%
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| Administration Time | 38 days | ||||
| Administration Dosage | 1.25 mg/kg | ||||
| MOA of PDC |
Collectively, our data demonstrate that Cltx within ER-472 acts a cryptic peptide which is metabolized to peptides with C-terminal R-COOH in the tumor microenvironment. These peptides bind to tumor cell NRP1 to increase drug uptake, which consequently boosts the antitumor effect.
|
||||
| Description |
At the MTD dose, ER-472 treatment resulted in significant antitumor activity in all 3 models, but at 1/2 MTD no antitumor activity was observed in MIA PaCa-2 or BxPC-3 xenografts. In contrast, a much wider therapeutic window was observed for ER-472 in PC-3 xenografts: tumor regression and several tumor cures were observed at 1/2 MTD and significant antitumor activity was also recorded at the 1/4 MTD dose.
Click to Show/Hide
|
||||
| In Vivo Model | PC-3 xenograft model. | ||||
| Experiment 6 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Tumor | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
100%
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| Administration Time | 30 days | ||||
| Administration Dosage | 2.5 mg/kg | ||||
| MOA of PDC |
Collectively, our data demonstrate that Cltx within ER-472 acts a cryptic peptide which is metabolized to peptides with C-terminal R-COOH in the tumor microenvironment. These peptides bind to tumor cell NRP1 to increase drug uptake, which consequently boosts the antitumor effect.
|
||||
| Description |
At the MTD dose, ER-472 treatment resulted in significant antitumor activity in all 3 models, but at 1/2 MTD no antitumor activity was observed in MIA PaCa-2 or BxPC-3 xenografts. In contrast, a much wider therapeutic window was observed for ER-472 in PC-3 xenografts: tumor regression and several tumor cures were observed at 1/2 MTD and significant antitumor activity was also recorded at the 1/4 MTD dose.
Click to Show/Hide
|
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| In Vivo Model | MIA PaCa-2 xenograft model. | ||||
References