Drug Information
General Information of This Drug
| Drug ID | DRG00058 | |||||
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| Drug Name | Cryptophycin analog | |||||
| Target(s) | Microtubule (MT) | Target Info | ||||
| Structure |
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| Formula |
C47H68ClN5O7S
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| #Ro5 Violations (Lipinski): 3 | Molecular Weight (mw) | 882.609 | ||||
| Lipid-water partition coefficient (xlogp) | 6.3464 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 3 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 10 | |||||
| Rotatable Bond Count (rotbonds) | 14 | |||||
| Canonical smiles |
COc1ccc(CC2NC(=O)C=CCC(C(C)C3OC3c3ccc(CN4CCN(CCC(C)(C)SC)CC4)cc3)OC(=O)C(CC(C)C)NC(=O)C(C)(C)CNC2=O)cc1Cl
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| InChI |
InChI=1S/C47H68ClN5O7S/c1-30(2)25-37-44(56)59-38(31(3)41-42(60-41)34-16-13-32(14-17-34)28-53-23-21-52(22-24-53)20-19-47(6,7)61-9)11-10-12-40(54)50-36(27-33-15-18-39(58-8)35(48)26-33)43(55)49-29-46(4,5)45(57)51-37/h10,12-18,26,30-31,36-38,41-42H,11,19-25,27-29H2,1-9H3,(H,49,55)(H,50,54)(H,51,57)/b12-10+/t31-,36+,37-,38-,41+,42+/m0/s1
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| InChIKey |
MBBGBLPGZZBLNN-BJKDTTSBSA-N
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Each Peptide-drug Conjugate Related to This Drug
Full Information of The Activity Data of The PDC(s) Related to This Drug
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% | |||
| 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% | |||
| 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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| 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% | |||
| 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.
|
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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 | 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% | |||
| 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% | |||
| 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% | |||
| 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