Linker Information
General Information of This Linker
| Linker ID |
LIN0YXWRQ
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| Linker Name |
Mal-Val-Cit
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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 |
C20H32N6O7
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| Isosmiles |
CCC(NCCNC(=O)CCCN1C(=O)C=CC1=O)C(=O)NC(CCCNC(N)=O)C(=O)O
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| InChI |
InChI=1S/C20H32N6O7/c1-2-13(18(30)25-14(19(31)32)5-3-9-24-20(21)33)22-10-11-23-15(27)6-4-12-26-16(28)7-8-17(26)29/h7-8,13-14,22H,2-6,9-12H2,1H3,(H,23,27)(H,25,30)(H,31,32)(H3,21,24,33)
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| InChIKey |
VOSBZJYYHPWAPI-UHFFFAOYSA-N
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| Pharmaceutical Properties |
Molecule Weight
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468.511
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Polar area
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200.03
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Complexity
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33
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xlogp Value
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-1.8061
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Heavy Count
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33
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Rot Bonds
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16
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Hbond acc
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7
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Hbond Donor
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6
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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
BMS-936561 [Phase 1 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | stable disease (SD) |
69%
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| Patients Enrolled |
Eligible patients must have ECOG 0-2 and meet tumor-specific criteria: ccRCC patients must have advanced/recurrent disease failing ≥1 prior therapy; B-NHL patients must have relapsed/refractory disease failing ≥1 prior therapy. All subjects must have measurable disease (unidimensional for ccRCC, bidimensional for B-NHL) and provide CD70+ tumor tissue (archived/fresh). Key exclusions include prior anti-CD70 therapy, severe mAb hypersensitivity, active CNS lymphoma, infections, bleeding disorders, active autoimmune disease requiring immunosuppression, or substance abuse.
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| Administration Dosage |
Assigned Interventions: Single dose of MDX-1203 will be administered every 21 days as an intravenous (i.v.) infusion. Subjects will receive one dose of MDX-1203.
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| Related Clinical Trial | |||||
| NCT Number | NCT00944905 | Clinical Status | PHASE1 | ||
| Clinical Description |
A Phase I, Multicenter, Open-Label, Dose-Escalation, Multidose Study of MDX-1203 in Subjects With Advanced/Recurrent Clear Cell Renal Cell Carcinoma or Relapsed/Refractory B-Cell Non Hodgkin's Lymphoma
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| Primary Endpoint |
The study evaluates the safety profile of MDX-1203 and determines the maximum tolerated dose (MTD) with assessment conducted over up to 17 treatment cycles.
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| Other Endpoint |
Biomarker analysis includes assessment of CD70+ tumor incidence in the target population, evaluated during the screening phase.
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| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT00944905 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1, multicenter, open-label, dose-escalation, multidose study of MDX-1203 in subjects with advanced/recurrent clear cell renal cell carcinoma or relapsed/refractory B-cell non Hodgkin's lymphoma.
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| Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
| Patients Enrolled |
Advanced or recurrent clear cell renal cell carcinoma (ccRCC) or relapsed or refractory B-non Hodgkin lymphoma (NHL), life expectancy of 12 weeks; ECOG performance status of 0-2; measurable disease by RECIST 1.1 criteria for ccRCC and by IWG 2007 criteria for B-NHL as well as adequate hematologic, renal and liver function parameters.
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| Administration Dosage |
0.50, 1.00, 2.00, 4.00, 8.00, 15.00 mg/kg administered every 21 days in a 42 day cycle for a maximum of 17 cycles, IV.
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| Related Clinical Trial | |||||
| NCT Number | NCT00944905 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1, multicenter, open-label, dose-escalation, multidose study of MDX-1203 in subjects with advanced/recurrent clear cell renal cell carcinoma or relapsed/refractory B-cell non Hodgkin's lymphoma.
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| Primary Endpoint |
The highest best tolerated dose and the recommended dose for future studies was 8 mg/kg dose.There was no MTD determined during the acute toxicity assessment window according to protocol-defined DLT according to protocol-defined DLT. There was disease stabilization in 18 of 26 patients (69.23%) without correlation with received dose.
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References