Linker Information
General Information of This Linker
| Linker ID |
LIN0MCOGM
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| Linker Name |
LPETG-Gly5-EDA
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| Linker Type |
Sortase-based site-specific conjugation linker
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| Antibody-Linker Relation |
Uncleavable
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| Structure |
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| Formula |
C12H23N7O5
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| Isosmiles |
NCCNC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)CN
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| InChI |
InChI=1S/C12H23N7O5/c13-1-2-15-9(21)4-17-11(23)6-19-12(24)7-18-10(22)5-16-8(20)3-14/h1-7,13-14H2,(H,15,21)(H,16,20)(H,17,23)(H,18,22)(H,19,24)
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| InChIKey |
APPZOWUYWPMKOP-UHFFFAOYSA-N
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| Pharmaceutical Properties |
Molecule Weight
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345.36
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Polar area
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197.54
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Complexity
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24
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xlogp Value
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-5.5152
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Heavy Count
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24
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Rot Bonds
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11
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Hbond acc
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7
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Hbond Donor
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7
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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
NBE-002 [Phase 1/2 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Patients Enrolled |
Eligibility requires age ≥18, progressive advanced tumors (Phase 1: any solid tumor refractory to standard therapy; Phase 2: TNBC ≤3L or other solid tumors ≤3L), measurable disease (Phase 2 only), ECOG 0-2 (Phase 1) or 0-1 (Phase 2), and adequate organ function. Key exclusions include prior ROR1-targeting therapy, active CNS metastases, unresolved Grade >1 toxicity from prior treatments, recent anticancer therapies/surgeries, significant comorbidities, and secondary malignancies within 3 years.
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| Administration Dosage |
NBE-002 will be given intravenously on Day 1 of repeated 28-day cycles.
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| Related Clinical Trial | |||||
| NCT Number | NCT04441099 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description |
A First-in-Human, Phase 1/2 Study of NBE-002, an Anti-ROR1 Antibody Drug Conjugate, in Patients With Advanced Solid Tumors
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| Primary Endpoint |
The Phase 1 portion focuses on determining the RP2D through DLT assessments over 48 months, while Phase 2 evaluates anti-tumor activity per RECIST v1.1 for up to 60 months.
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| Other Endpoint |
Safety monitoring (CTCAE v5.0) and preliminary efficacy (RECIST v1.1) run through 48-60 months, with additional PK (NBE-002 concentrations) and immunogenicity (anti-drug antibodies) profiling.
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Trastuzumab-PNUEDAGly5 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 100% | Positive HER2 expression (HER2 +++/++) | ||
| Method Description |
1,000,000 EMT6 mouse breast cancer cells expressing human HER-2 previously determined to be suitable for in vivo growth, were implanted into theright mammary fat pads of female Balb/c mice. Animals were treated onthe same day (day 13) and 7 days later (day 20) byintravenous injection of the reference ADC Kadcyla (15 mg/kg), Trastuzumab-PNU-EDA-Glys (1 mg/kg) or vehicle control.
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| In Vivo Model | EMT6 CDX model (Expressing hHER2) | ||||
| In Vitro Model | Mammary gland malignant neoplasms | EMT6 cells (High HER2 expression) | CVCL_1923 | ||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
6.9 ng/mL
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High CD30 expression (CD30 +++) | ||
| Method Description |
Dose response of the cytotoxic effects of the indicated ADCs on human Non-Hodgkin lymphoma cell line Karpas-299, and on human Hodgkin lymphoma cell line L428 cells.
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| In Vitro Model | ALK-positive anaplastic large cell lymphoma | Karpas-299 cells | CVCL_1324 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | < 10 ug/mL | Low CD30 expression (CD30 +) | ||
| Method Description |
Dose response of the cytotoxic effects of the indicated ADCs on human Non-Hodgkin lymphoma cell line Karpas-299, and on human Hodgkin lymphoma cell line L428 cells.
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| In Vitro Model | Hodgkin lymphoma | L-428 cells | CVCL_1361 | ||
Brentuximab-PNUEDAGly5 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
4.8 ng/mL
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High HER2 expression (HER2 +++) | ||
| Method Description |
For this, cells were plated on 96 well plates in 100 ul DMEM/10% FCS at adensity of 104 cells per well and assays were performed.
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| In Vitro Model | Breast adenocarcinoma | SK-BR-3 cells | CVCL_0033 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
11 ng/mL
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Low HER2 expression (HER2 +) | ||
| Method Description |
For this, cells were plated on 96 well plates in 100 ul DMEM/10% FCS at adensity of 104 cells per well and assays were performed.
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| In Vitro Model | Invasive breast carcinoma | T-47D cells | CVCL_0553 | ||
References