Linker Information

General Information of This Linker
Linker ID
LIN0UVPJN
Linker Name
Mc-Val-Cit
Linker Type
Cathepsin-cleavable linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C21H33N5O7
Isosmiles
[H]OC(=O)[C@@]([H])(N([H])C(=O)[C@]([H])(N([H])C(=O)C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N1C(=O)C([H])=C([H])C1=O)C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=O)N([H])[H]
PubChem CID
154803602
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
InChIKey
WXNPFVBGHOJJLL-KBXCAEBGSA-N
IUPAC Name
(2S)-5-(carbamoylamino)-2-[[(2R)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoic acid
Pharmaceutical Properties
Molecule Weight
467.523
Polar area
188
Complexity
467.2379984
xlogp Value
-0.3695
Heavy Count
33
Rot Bonds
17
Hbond acc
7
Hbond Donor
5
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 (Terminated)]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Objective Response Rate (ORR)
2.00% (All escalation, BMS-986148 monotherapy)
6.00% (All expansion, BMS-986148 monotherapy)
4.00% (Mesothelioma expansion, BMS-986148 monotherapy)
9.00% (Ovarian expansion)
20.00% (All, BMS-986148 + nivolumab)
23.00% (Mesothelioma, BMS-986148 + nivolumab)
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).
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.
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.
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.
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.
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.
References
Ref 1 Phase I/IIa Trial of BMS-986148, an Anti-mesothelin Antibody-drug Conjugate, Alone or in Combination with Nivolumab in Patients with Advanced Solid Tumors. Clin Cancer Res. 2022 Jan 1;28(1):95-105.
Ref 2 A Phase I/IIa Study of BMS-986148, a Mesothelin Directed Antibody Drug Conjugate, in Subjects With Select Advanced Solid Tumors, NCT02341625
Ref 3 A Phase 1 Study of the Safety and Tolerability of BMS 986148 in Subjects With Advanced and/or Metastatic Solid Tumors, NCT02884726