Linker Information
General Information of This Linker
| Linker ID |
LIN0TFFTA
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| Linker Name |
ThioBridge-PEG24-Val-Ala-PAB
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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 |
C83H143Br2N7O32
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| Isosmiles |
COCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOC CNC(=O)C(CCC(=O)NC(C(=O)NC(CCCNC(N)=O)C(=O)Nc1ccc(CO)cc1)C(C)C)NC(=O)c1ccc(C(=O)C(CBr)CBr)cc1
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| InChI |
InChI=1S/C83H143Br2N7O32/c1-68(2)77(82(99)91-74(5-4-16-88-83(86)100)81(98)89-73-12-6-69(67-93)7-13-73)92-76(94)15-14-75(90-79(96)71-10-8-70(9-11-71)78(95)72(65-84)66-85)80(97)87-17-18-102-21-22-104-25-26-106-29-30-108-33-34-110-37-38-112-41-42-114-45-46-116-49-50-118-53-54-120-57-58-122-61-62-124-64-63-123-60-59-121-56-55-119-52-51-117-48-47-115-44-43-113-40-39-111-36-35-109-32-31-107-28-27-105-24-23-103-20-19-101-3/h6-13,68,72,74-75,77,93H,4-5,14-67H2,1-3H3,(H,87,97)(H,89,98)(H,90,96)(H,91,99)(H,92,94)(H3,86,88,100)
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| InChIKey |
LPYQQMBHYWGDNW-UHFFFAOYSA-N
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| Pharmaceutical Properties |
Molecule Weight
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1910.882
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Polar area
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459.44
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Complexity
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124
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xlogp Value
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2.5034
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Heavy Count
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124
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Rot Bonds
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93
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Hbond acc
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32
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Hbond Donor
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8
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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
OBI-999 [Phase 1/2]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Patients Enrolled |
Advanced solid tumors that had been previously treated with standard-of-care therapy and their physicians had determined that such therapy was no longer effective, or patients had declined to receive further standard-of-care treatments.
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| Administration Dosage |
The starting dose of 0.40 mg/kg on day 1 of each 21-day cycle; A standard 3 + 3 dose-escalation design was used, and doses of 0.80, 1.20, and 1.60 mg/kg were also administered on day 1 of each 21-day cycle; intravenous infusion over 60 minutes.
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| Related Clinical Trial | |||||
| NCT Number | NCT04084366 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1/2, open-label, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics, and therapeutic activity of OBI-999 in patients with advanced solid tumors.
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| Primary Endpoint |
The incidence of dose-limiting toxicities and adverse events and determination of the maximum tolerated dose (MTD)/recommended phase II dose.
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Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 34.00% (Day 26) | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 0.3 mg/kg, qw*6.
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| In Vivo Model | MCF-7 CDX model | ||||
| In Vitro Model | Invasive breast carcinoma | MCF-7 cells | CVCL_0031 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 60.00% (Day 77) | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 1 mg/kg, qw*6.
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| In Vivo Model | MCF-7 CDX model | ||||
| In Vitro Model | Invasive breast carcinoma | MCF-7 cells | CVCL_0031 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 83.00% (Day 53) | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 1 mg/kg, qw*4.
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| In Vivo Model | NCI-N87 CDX model | ||||
| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 85.00% (Day 25) | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 10 mg/kg, qw*4.
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| In Vivo Model | NCI-H526 CDX model | ||||
| In Vitro Model | Lung small cell carcinoma | NCI-H526 cells | CVCL_1569 | ||
| Experiment 5 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 95.00% (Day 77) | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 10 mg/kg, qw*2.
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| In Vivo Model | MCF-7 CDX model | ||||
| In Vitro Model | Invasive breast carcinoma | MCF-7 cells | CVCL_0031 | ||
| Experiment 6 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 97.00% (Day 53) | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 10 mg/kg, qw*4.
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| In Vivo Model | NCI-N87 CDX model | ||||
| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
| Experiment 7 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 97.00% (Day 53) | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 1-3 mg/kg, qw*4.
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| In Vivo Model | NCI-N87 CDX model | ||||
| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
| Experiment 8 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 98.00% (Day 77) | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 3 mg/kg, qw*6.
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| In Vivo Model | MCF-7 CDX model | ||||
| In Vitro Model | Invasive breast carcinoma | MCF-7 cells | CVCL_0031 | ||
| Experiment 9 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 99.00% (Day 37) | Positive Globo H expression (Globo H+++/++) | ||
| Method Description |
Mice were treated with an intravenous dose of the ADCs at 10 mg/kg, qw*4.
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| In Vivo Model | HPAC CDX model | ||||
| In Vitro Model | Pancreatic adenocarcinoma | HPAC cells | CVCL_3517 | ||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 70.70% | |||
| Method Description |
In vivo , In each animal study,the antitumor efficacy was evaluated with doses of 1.00, 3.00, or 10.00 mg/kg of OBI-999 via i.v. injection. In NCI-N87 xenograft model,treatment groups of MMAE 0.191 mg/kg and Ctrl-ADC 3 mg/kg were also included. Each study utilized 6 to 8 mice per group.
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| In Vitro Model | Breast adenocarcinoma | MDA-MB-231 cells | CVCL_0062 | ||
| Breast adenocarcinoma | HCC1428 cells | CVCL_1252 | |||
References
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