Linker Information
General Information of This Linker
| Linker ID |
LIN0UVPJN
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| Linker Name |
Mc-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 |
C21H33N5O7
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| Isosmiles |
CC(C)[C@H](C(=O)N[C@@H](CCCNC(=O)N)C(=O)O)NC(=O)CCCCCN1C(=O)C=CC1=O
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| PubChem CID | ||||||
| InChI |
InChI=1S/C21H33N5O7/c1-13(2)18(19(30)24-14(20(31)32)7-6-11-23-21(22)33)25-15(27)8-4-3-5-12-26-16(28)9-10-17(26)29/h9-10,13-14,18H,3-8,11-12H2,1-2H3,(H,24,30)(H,25,27)(H,31,32)(H3,22,23,33)/t14-,18+/m0/s1
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| InChIKey |
WXNPFVBGHOJJLL-KBXCAEBGSA-N
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| IUPAC Name |
(2S)-5-(carbamoylamino)-2-[[(2R)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoic acid
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| Pharmaceutical Properties |
Molecule Weight
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467.5
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Polar area
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188
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Complexity
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763
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xlogp Value
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-0.4
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Heavy Count
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33
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Rot Bonds
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15
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Hbond acc
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7
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Hbond Donor
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5
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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-986148 [Phase 1/2 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
2.00
6.00 4.00 9.00 20.00 23.00 % |
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| Patients Enrolled |
Pleural or peritoneal mesothelioma (except sarcomatoid mesothelioma), ovarian cancer (except mucinous carcinoma), pancreatic cancer, gastric cancer, or non-small cell lung cancer (adenocarcinoma only).
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| Administration Dosage |
BMS-986148 monotherapy (0.1-1.6 mg/kg intravenously (i.v.) every 3 weeks or 0.4 or 0.6 mg/kg i.v. once weekly; n = 96) or BMS-986148 0.8 mg/kg + nivolumab 360 mg i.v. every 3 weeks (n = 30). The primary endpoint was safety and tolerability.
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| Related Clinical Trial | |||||
| NCT Number | NCT02341625 | Clinical Status | Phase 1/2a | ||
| Clinical Description |
A phase 1/2a study of BMS-986148, a mesothelin directed antibody drug conjugate, in subjects with select advanced solid tumors.
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| Primary Endpoint |
The MTD and the recommended dose for the part 2 monotherapy expansion is BMS-986148 1.20 mg/kg every 3 weeks dose level. The MTD in the combination expansion cohort is BMS-986148 0.80 mg/kg + nivolumab 360 mg every 3 weeks.
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| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT02341625 | Clinical Status | Phase 1/2 | ||
| Clinical Description |
A phase 1/2a study of BMS-986148, a mesothelin directed antibody drug conjugate, in subjects with select advanced solid tumors.
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| Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT02884726 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1 study of the safety and tolerability of BMS 986148 in subjects with advanced and/or metastatic solid tumors.
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| Experiment 4 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
9%
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| Patients Enrolled |
Eligible participants (≥18 years, ECOG 0-1) must have mesothelin-positive measurable tumors (pancreatic/ovarian/gastric/NSCLC/mesothelioma) and ≥3-month life expectancy. Exclusions cover brain metastases, active/hepatitis infections, major surgery (<1 month), uncontrolled cardiac/liver/bone marrow dysfunction, or hypersensitivity to mesothelin antibodies/tubulysin/nivolumab-related agents.
Click to Show/Hide
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| Related Clinical Trial | |||||
| NCT Number | NCT02341625 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description |
A Phase I/IIa Study of BMS-986148, a Mesothelin Directed Antibody Drug Conjugate, in Subjects With Select Advanced Solid Tumors
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| Primary Endpoint |
Safety outcomes include adverse events (AEs, SAEs, discontinuations, deaths) and laboratory toxicity shifts (hematology/chemistry) from baseline to 100 days post-treatment (≤6 months), analyzed by NCT CTCAE v4.03 criteria and grouped by dose/regimen.
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| Other Endpoint |
Pharmacokinetics (Cmax, Tmax, Ctau, Ctrough, AUC (0-t), AUC[TAU]) are assessed during Cycle 1, with arithmetic %CV reported. Efficacy endpoints (up to 58 months) include best overall response (CR/PR/SD/PD), ORR, duration of response (DoR), progression-free survival (PFS), and PFS rates (4-12 months), stratified by tumor type (mesothelioma, pancreatic, ovarian, NSCLC, gastric). QTcF interval changes and ADA status are also evaluated by dose/regimen.
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| Experiment 5 Reporting the Activity Date of This ADC | [5] | ||||
| Patients Enrolled |
Eligible participants must have advanced/metastatic mesothelin-expressing solid tumors, progression/intolerance to standard therapy, measurable disease per RECIST, and ECOG 0-1. Exclusions include brain metastases, uncontrolled cardiovascular disease, eye/peripheral neuropathy, hepatitis B/C infection, or other protocol-specified conditions.
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| Administration Dosage |
Specified dose on specified days
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| Related Clinical Trial | |||||
| NCT Number | NCT02884726 | Clinical Status | PHASE1 | ||
| Clinical Description |
A Phase 1 Study of the Safety and Tolerability of BMS 986148 in Subjects With Advanced and/or Metastatic Solid Tumors
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| Primary Endpoint |
Safety analysis covers adverse events (AEs/SAEs), including discontinuations and deaths, from Day 1 to 30 days post-treatment, with grading and laboratory toxicity shifts from baseline as key metrics for participant safety assessment.
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| Other Endpoint |
Pharmacokinetic parameters (Cmax, Tmax, AUC (0-T), AUC (TAU), Ctrough, etc.) and accumulation indices (AI) are evaluated from Day 1 to 84, alongside tumor response based on RECIST criteria post-BMS-986148 treatment to assess drug exposure and efficacy.
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wO2024140449A1 ADC1 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
5-50 nM
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| Method Description |
A Cell line test on OE-33
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| In Vitro Model | Barrett adenocarcinoma, Adenocarcinoma of the esophagus | OE-33 cells | CVCL_0471 | ||
wO2024140449A1 ADC2 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
5-50 nM
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| Method Description |
A Cell line test on OE-33
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| In Vitro Model | Barrett adenocarcinoma, Adenocarcinoma of the esophagus | OE-33 cells | CVCL_0471 | ||
References