Peptide-drug Conjugate Information
General Information of This Peptide-drug Conjugate (PDC)
| PDC ID |
PDC_00150
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| PDC Name |
ER-472
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| PDC Status |
Investigative
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| Indication |
In total 1 Indication(s)
Tumor
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| Structure |
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| Peptide Name |
Chlorotoxin
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Peptide Info | ||||
| Receptor Name |
Neuropilin-1 (NRP1)
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Receptor Info | ||||
| Drug Name |
Cryptophycin analog
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Drug Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Dimethyl disulfide
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Linker Info | ||||
| Formula |
C212H319ClN58O55S13
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| #Ro5 Violations (Lipinski): 5 | Molecular Weight | 5012.559 | ||||
| Lipid-water partition coefficient (xlogp) | -11.5995 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 56 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 74 | |||||
| Rotatable Bond Count (rotbonds) | 85 | |||||
Full List of Activity Data of This Peptide-drug Conjugate
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.
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|
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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
|
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| 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
|
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| 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