Linker Information
General Information of This Linker
| Linker ID |
LIN0WLMUR
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| Linker Name |
BCN-HydraSpace-Val-Ala-PABC
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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 |
C52H76N10O19S2
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| Isosmiles |
CC(NC(=O)C(NC(=O)OCCN(CCOC(=O)NC(C(=O)NC(C)C(=O)Nc1ccc(CO)cc1)C(C)C)S(=O)(=O)NC(=O)OCCOCCNS(=O)(=O)NC(=O)OCC1C2CCC#CCCC21)C(C)C)C(=O)Nc1ccc(CO)cc1
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| InChI |
InChI=1S/C52H76N10O19S2/c1-32(2)43(47(67)54-34(5)45(65)56-38-17-13-36(29-63)14-18-38)58-49(69)78-25-22-62(23-26-79-50(70)59-44(33(3)4)48(68)55-35(6)46(66)57-39-19-15-37(30-64)16-20-39)83(75,76)61-52(72)80-28-27-77-24-21-53-82(73,74)60-51(71)81-31-42-40-11-9-7-8-10-12-41(40)42/h13-20,32-35,40-44,53,63-64H,9-12,21-31H2,1-6H3,(H,54,67)(H,55,68)(H,56,65)(H,57,66)(H,58,69)(H,59,70)(H,60,71)(H,61,72)
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| InChIKey |
NNKFBMCYMVLPJI-UHFFFAOYSA-N
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| Pharmaceutical Properties |
Molecule Weight
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1209.365
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Polar area
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402.96
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Complexity
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83
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xlogp Value
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1.0492
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Heavy Count
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83
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Rot Bonds
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32
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Hbond acc
|
19
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Hbond Donor
|
11
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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
Mipasetamab uzoptirine [Phase 1]
Discovered Using Patient-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 35.00% (Day 65) | Positive AXL expression (AXL+++/++) | ||
| Method Description |
In vivo antitumor activity of ADCT-601 in BRCA1-mutated ovarian cancer PDX model. Single-dose (0.15 mg/kg,q.d.) ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
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| In Vivo Model | BRCA1-mutated ovarian cancer PDX model (PDX: CTG-0703) | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 57.40% (Day 21) | Positive AXL expression (AXL+++/++) | ||
| Method Description |
The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (0.075 mg/kg,q.d.). ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
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| In Vivo Model | Pancreatic cancer PDX model (PDX: PAXF1657) | ||||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 65.80% (Day 65) | Negative AXL expression (AXL-) | ||
| Method Description |
In vivo antitumor activity of ADCT-601 in BRCA1-mutated ovarian cancer PDX model. Single-dose (0.15 mg/kg,q.d.) ADCT-601 in combination with olaparib (50 mg/kg) and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
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| In Vivo Model | BRCA1-mutated ovarian cancer PDX model (PDX: CTG-0703) | ||||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 68.70% (Day 30) | Negative AXL expression (AXL-) | ||
| Method Description |
In vivo antitumor activity of ADCT-601 in a MMAE-resistant NCI-H1299 NSCLC model. Single-dose (0.50 mg/kg,q.d.) ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
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| In Vivo Model | MMAE-resistant non-small cell lung cancer PDX model (PDX: NCI-H1299) | ||||
| Experiment 5 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 72.10% (Day 30) | Positive AXL expression (AXL+++/++; 88,000 copy number) | ||
| Method Description |
In vivo antitumor activity of ADCT-601 in a MMAE-resistant NCI-H1299 NSCLC model. Single-dose (1.00 mg/kg,q.d.) ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
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| In Vivo Model | MMAE-resistant non-small cell lung cancer PDX model (PDX: NCI-H1299) | ||||
| Experiment 6 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 84.90% (Day 21) | Positive AXL expression (AXL+++/++; 88,000 copy number) | ||
| Method Description |
The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (0.15 mg/kg,q.d.). ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
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| In Vivo Model | Pancreatic cancer PDX model (PDX: PAXF1657) | ||||
| Experiment 7 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 96.90% (Day 21) | Positive AXL expression (AXL+++/++; 88,000 copy number) | ||
| Method Description |
The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (0.30 mg/kg,q.d.). ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
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| In Vivo Model | Pancreatic cancer PDX model (PDX: PAXF1657) | ||||
| Experiment 8 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 98.50% (Day 51) | Positive AXL expression (AXL+++/++; 36,000 copy number) | ||
| Method Description |
The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (1 mg/kg,q.d.) 0.ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
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| In Vivo Model | Esophageal caner PDX model (PDX: ES0195) | ||||
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 69.40% (Day 60) | Positive AXL expression (AXL+++/++) | ||
| Method Description |
The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (0.30 mg/kg,q.d.). ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
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| In Vivo Model | kidney cancer CDX model | ||||
| In Vitro Model | Renal cell carcinoma | SN12C cells | CVCL_1705 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 86.20% (Day 60) | Positive AXL expression (AXL+++/++) | ||
| Method Description |
The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (0.60 mg/kg,q.d.). ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
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| In Vivo Model | kidney cancer CDX model | ||||
| In Vitro Model | Renal cell carcinoma | SN12C cells | CVCL_1705 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 97.60% (Day 23) | Positive AXL expression (AXL+++/++) | ||
| Method Description |
The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (1.00 mg/kg,q.d.). ADCT-601 and isotype-control ADC were administered intravenously (day 1) to treatment groups of 10 mice.
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| In Vivo Model | Triple-negative breast cancer CDX model | ||||
| In Vitro Model | Breast adenocarcinoma | MDA-MB-231 cells | CVCL_0062 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 98.50% (Day 60) | Positive AXL expression (AXL+++/++) | ||
| Method Description |
The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (1.00 mg/kg,q.d.). ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
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| In Vivo Model | Kidney cancer CDX model | ||||
| In Vitro Model | Renal cell carcinoma | SN12C cells | CVCL_1705 | ||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.02 nM
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Positive AXL expression (AXL+++/++; 46,000 copy number) | ||
| Method Description |
In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO2-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.
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| In Vitro Model | Lung adenocarcinoma | SK-LU-1 cells | CVCL_0629 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.11 nM
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Positive AXL expression (AXL+++/++; 88,000 copy number) | ||
| Method Description |
In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO2-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.
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| In Vitro Model | Ovarian serous cystadenocarcinoma | SK-OV-3 cells | CVCL_0532 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.35 nM
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Positive AXL expression (AXL+++/++; 79,000 copy number) | ||
| Method Description |
In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO2-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.
Click to Show/Hide
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| In Vitro Model | Breast adenocarcinoma | MDA-MB-231 cells | CVCL_0062 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.47 nM
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Positive AXL expression (AXL+++/++; 24,000 copy number) | ||
| Method Description |
In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO2-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.
Click to Show/Hide
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| In Vitro Model | Pancreatic ductal adenocarcinoma | PANC-1 cells | CVCL_0480 | ||
| Experiment 5 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.59 nM
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Positive AXL expression (AXL+++/++; 23,000 copy number) | ||
| Method Description |
In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO2-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.
Click to Show/Hide
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| In Vitro Model | Glioblastoma | A-172 cells | CVCL_0131 | ||
| Experiment 6 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.83 nM
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Positive AXL expression (AXL+++/++; 79,000 copy number) | ||
| Method Description |
In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO2-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.
Click to Show/Hide
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| In Vitro Model | Renal cell carcinoma | SN12C cells | CVCL_1705 | ||
| Experiment 7 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
2.20 nM
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Positive AXL expression (AXL+++/++; 20,000 copy number) | ||
| Method Description |
In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO2-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.
Click to Show/Hide
|
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| In Vitro Model | Lung large cell carcinoma | NCI-H1299 cells | CVCL_0060 | ||
| Experiment 8 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
9.29 nM
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Positive AXL expression (AXL+++/++; 79,000 copy number) | ||
| Method Description |
In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO2-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.
Click to Show/Hide
|
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| In Vitro Model | Breast adenocarcinoma | MDA-MB-361 cells | CVCL_0620 | ||
| Experiment 9 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
14.62 nM
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Positive AXL expression (AXL+++/++; 36,000 copy number) | ||
| Method Description |
In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO2-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.
Click to Show/Hide
|
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| In Vitro Model | ALK-positive anaplastic large cell lymphoma | Karpas-299 cells | CVCL_1324 | ||
References
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