Peptide Information
General Information of This Peptide
| Peptide ID |
PEP00098
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| Peptide Name |
αvβ6-BP
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| Structure |
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| Sequence |
NAVPNLRGDLQVLAQRVART
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| Peptide Type |
Linear
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| Receptor Name |
Integrin alpha-V; Integrin beta-6 (ITGAV; ITGB6)
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Receptor Info | ||||
| PDC Transmembrane Types | Cell-penetrating peptides (CPPs) | |||||
| Formula |
C93H163N33O28
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| Isosmiles |
[H]NC(=O)CC[C@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)N[H])NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCC/N=C(/N)N[H])NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)N[H])NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)N[H])N[H])C(C)C)C(C)C)C(=O)N[C@@H](CCC/N=C(/N)N[H])C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC/N=C(/N)N[H])C(=O)N[C@]([H])(C(=O)O)[C@@H](C)O[H])C(C)C
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| InChI |
InChI=1S/C93H163N33O28/c1-40(2)33-56(81(144)110-46(13)72(135)114-54(25-27-62(95)128)77(140)116-53(23-19-31-107-93(103)104)78(141)122-68(43(7)8)87(150)111-47(14)73(136)113-52(22-18-30-106-92(101)102)79(142)125-71(49(16)127)90(153)154)121-88(151)69(44(9)10)123-80(143)55(26-28-63(96)129)117-83(146)58(35-42(5)6)119-85(148)60(38-67(133)134)112-66(132)39-108-76(139)51(21-17-29-105-91(99)100)115-82(145)57(34-41(3)4)118-84(147)59(37-65(98)131)120-86(149)61-24-20-32-126(61)89(152)70(45(11)12)124-74(137)48(15)109-75(138)50(94)36-64(97)130/h40-61,68-71,127H,17-39,94H2,1-16H3,(H2,95,128)(H2,96,129)(H2,97,130)(H2,98,131)(H,108,139)(H,109,138)(H,110,144)(H,111,150)(H,112,132)(H,113,136)(H,114,135)(H,115,145)(H,116,140)(H,117,146)(H,118,147)(H,119,148)(H,120,149)(H,121,151)(H,122,141)(H,123,143)(H,124,137)(H,125,142)(H,133,134)(H,153,154)(H4,99,100,105)(H4,101,102,106)(H4,103,104,107)/t46-,47-,48-,49+,50-,51-,52-,53-,54-,55-,56-,57-,58-,59-,60-,61-,68-,69-,70-,71-/m0/s1
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| InChIKey |
TXSIUNXQNBOQGC-OXSXEHGKSA-N
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| Pharmaceutical Properties |
Molecule Weight
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2191.53
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Polar area
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1030.52
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Complexity
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2190.234532
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xlogp Value
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-12.7888
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Heavy Count
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154
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Rot Bonds
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74
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Hbond acc
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30
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Hbond Donor
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32
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Each Peptide-drug Conjugate Related to This Peptide
Full Information of The Activity Data of The PDC(s) Related to This Peptide
[64Cu]PDC-1 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Melanoma | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.058 ± 0.003 nM
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| Administration Time | 48 h | ||||
| Evaluation Method | WST-1 assay | ||||
| MOA of PDC |
Many anticancer drugs exhibit high systemic off-target toxicities causing severe side effects. Peptide-drug conjugates (PDCs) that target tumor-specific receptors such as integrin vβ6 are emerging as powerful tools to overcome these challenges. The development of an integrin vβ6-selective PDC was achieved by combining the therapeutic efficacy of the cytotoxic drug monomethyl auristatin E with the selectivity of the vβ6-binding peptide (vβ6-BP) and with the ability of positron emission tomography (PET) imaging by copper-64. The [64Cu]PDC-1 was produced efficiently and in high purity. The PDC exhibited high human serum stability, integrin vβ6-selective internalization, cell binding, and cytotoxicity. Integrin vβ6-selective tumor accumulation of the [64Cu]PDC-1 was visualized with PET-imaging and corroborated by biodistribution, and [64Cu]PDC-1 showed promising in vivo pharmacokinetics. The [natCu]PDC-1 treatment resulted in prolonged survival of mice bearing vβ6 (+) tumors (median survival: 77 days, vs vβ6 (-) tumor group 49 days, and all other control groups 37 days).
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| Description |
Both NH2-PDC-1 and [natCu]PDC-1 exhibited integrin v6-dependent cytotoxicity, only reducing cell viability of the v6-positive cells. For [natCu]PDC-1 high cytotoxicity was observed in DX3puro6 (+) cells (EC50: 0.058 ± 0.003 nM) with no observable cytotoxic effects in the DX3puro (-) cells, while free MMAE had almost equal cytotoxicity to both DX3puro6 (+) and DX3puro cells (-) (EC50: 0.14-0.15 nM). The pancreatic cells also showed v6-dependent cytotoxicity for [natCu]PDC-1 (EC50: BxPC-3 65.1 ± 10.6 nM) and required high concentrations of ≥250 nM for noticeable cytotoxic effects in the minimally integrin v6-expressing MIA PaCa-2 cells. Again, free, non-targeted MMAE exhibited nondiscriminatory cytotoxicity among the pancreatic cells with an effective concentration range of EC50 = 0.16-0.5 nM. Peptides NH2-2 and [natCu]2 were not toxic to any cells.
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| In Vitro Model | Melanoma | DX3-puro/beta6 cell | CVCL_1D33 | ||
| Experiment 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Melanoma | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | > 5 nM | |||
| Administration Time | 48 h | ||||
| Evaluation Method | WST-1 assay | ||||
| MOA of PDC |
Many anticancer drugs exhibit high systemic off-target toxicities causing severe side effects. Peptide-drug conjugates (PDCs) that target tumor-specific receptors such as integrin vβ6 are emerging as powerful tools to overcome these challenges. The development of an integrin vβ6-selective PDC was achieved by combining the therapeutic efficacy of the cytotoxic drug monomethyl auristatin E with the selectivity of the vβ6-binding peptide (vβ6-BP) and with the ability of positron emission tomography (PET) imaging by copper-64. The [64Cu]PDC-1 was produced efficiently and in high purity. The PDC exhibited high human serum stability, integrin vβ6-selective internalization, cell binding, and cytotoxicity. Integrin vβ6-selective tumor accumulation of the [64Cu]PDC-1 was visualized with PET-imaging and corroborated by biodistribution, and [64Cu]PDC-1 showed promising in vivo pharmacokinetics. The [natCu]PDC-1 treatment resulted in prolonged survival of mice bearing vβ6 (+) tumors (median survival: 77 days, vs vβ6 (-) tumor group 49 days, and all other control groups 37 days).
Click to Show/Hide
|
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| Description |
Both NH2-PDC-1 and [natCu]PDC-1 exhibited integrin v6-dependent cytotoxicity, only reducing cell viability of the v6-positive cells. For [natCu]PDC-1 high cytotoxicity was observed in DX3puro6 (+) cells (EC50: 0.058 ± 0.003 nM) with no observable cytotoxic effects in the DX3puro (-) cells, while free MMAE had almost equal cytotoxicity to both DX3puro6 (+) and DX3puro cells (-) (EC50: 0.14-0.15 nM). The pancreatic cells also showed v6-dependent cytotoxicity for [natCu]PDC-1 (EC50: BxPC-3 65.1 ± 10.6 nM) and required high concentrations of ≥250 nM for noticeable cytotoxic effects in the minimally integrin v6-expressing MIA PaCa-2 cells. Again, free, non-targeted MMAE exhibited nondiscriminatory cytotoxicity among the pancreatic cells with an effective concentration range of EC50 = 0.16-0.5 nM. Peptides NH2-2 and [natCu]2 were not toxic to any cells.
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| In Vitro Model | Melanoma | DX3-puro cell | CVCL_1D33 | ||
| Experiment 3 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Pancreatic cancer | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
65.1 ± 10.6 nM
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| Administration Time | 48 h | ||||
| Evaluation Method | WST-1 assay | ||||
| MOA of PDC |
Many anticancer drugs exhibit high systemic off-target toxicities causing severe side effects. Peptide-drug conjugates (PDCs) that target tumor-specific receptors such as integrin vβ6 are emerging as powerful tools to overcome these challenges. The development of an integrin vβ6-selective PDC was achieved by combining the therapeutic efficacy of the cytotoxic drug monomethyl auristatin E with the selectivity of the vβ6-binding peptide (vβ6-BP) and with the ability of positron emission tomography (PET) imaging by copper-64. The [64Cu]PDC-1 was produced efficiently and in high purity. The PDC exhibited high human serum stability, integrin vβ6-selective internalization, cell binding, and cytotoxicity. Integrin vβ6-selective tumor accumulation of the [64Cu]PDC-1 was visualized with PET-imaging and corroborated by biodistribution, and [64Cu]PDC-1 showed promising in vivo pharmacokinetics. The [natCu]PDC-1 treatment resulted in prolonged survival of mice bearing vβ6 (+) tumors (median survival: 77 days, vs vβ6 (-) tumor group 49 days, and all other control groups 37 days).
Click to Show/Hide
|
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| Description |
Both NH2-PDC-1 and [natCu]PDC-1 exhibited integrin v6-dependent cytotoxicity, only reducing cell viability of the v6-positive cells. For [natCu]PDC-1 high cytotoxicity was observed in DX3puro6 (+) cells (EC50: 0.058 ± 0.003 nM) with no observable cytotoxic effects in the DX3puro (-) cells, while free MMAE had almost equal cytotoxicity to both DX3puro6 (+) and DX3puro cells (-) (EC50: 0.14-0.15 nM). The pancreatic cells also showed v6-dependent cytotoxicity for [natCu]PDC-1 (EC50: BxPC-3 65.1 ± 10.6 nM) and required high concentrations of ≥250 nM for noticeable cytotoxic effects in the minimally integrin v6-expressing MIA PaCa-2 cells. Again, free, non-targeted MMAE exhibited nondiscriminatory cytotoxicity among the pancreatic cells with an effective concentration range of EC50 = 0.16-0.5 nM. Peptides NH2-2 and [natCu]2 were not toxic to any cells.
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| In Vitro Model | Pancreatic ductal adenocarcinoma | BxPC-3 (+) cells | CVCL_0186 | ||
| Experiment 4 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Pancreatic cancer | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | > 250 nM | |||
| Administration Time | 48 h | ||||
| Evaluation Method | WST-1 assay | ||||
| MOA of PDC |
Many anticancer drugs exhibit high systemic off-target toxicities causing severe side effects. Peptide-drug conjugates (PDCs) that target tumor-specific receptors such as integrin vβ6 are emerging as powerful tools to overcome these challenges. The development of an integrin vβ6-selective PDC was achieved by combining the therapeutic efficacy of the cytotoxic drug monomethyl auristatin E with the selectivity of the vβ6-binding peptide (vβ6-BP) and with the ability of positron emission tomography (PET) imaging by copper-64. The [64Cu]PDC-1 was produced efficiently and in high purity. The PDC exhibited high human serum stability, integrin vβ6-selective internalization, cell binding, and cytotoxicity. Integrin vβ6-selective tumor accumulation of the [64Cu]PDC-1 was visualized with PET-imaging and corroborated by biodistribution, and [64Cu]PDC-1 showed promising in vivo pharmacokinetics. The [natCu]PDC-1 treatment resulted in prolonged survival of mice bearing vβ6 (+) tumors (median survival: 77 days, vs vβ6 (-) tumor group 49 days, and all other control groups 37 days).
Click to Show/Hide
|
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| Description |
Both NH2-PDC-1 and [natCu]PDC-1 exhibited integrin v6-dependent cytotoxicity, only reducing cell viability of the v6-positive cells. For [natCu]PDC-1 high cytotoxicity was observed in DX3puro6 (+) cells (EC50: 0.058 ± 0.003 nM) with no observable cytotoxic effects in the DX3puro (-) cells, while free MMAE had almost equal cytotoxicity to both DX3puro6 (+) and DX3puro cells (-) (EC50: 0.14-0.15 nM). The pancreatic cells also showed v6-dependent cytotoxicity for [natCu]PDC-1 (EC50: BxPC-3 65.1 ± 10.6 nM) and required high concentrations of ≥250 nM for noticeable cytotoxic effects in the minimally integrin v6-expressing MIA PaCa-2 cells. Again, free, non-targeted MMAE exhibited nondiscriminatory cytotoxicity among the pancreatic cells with an effective concentration range of EC50 = 0.16-0.5 nM. Peptides NH2-2 and [natCu]2 were not toxic to any cells.
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| In Vitro Model | Pancreatic ductal adenocarcinoma | MIA PaCa-2 cell | CVCL_0428 | ||
References