Linker Information

General Information of This Linker
Linker ID
LIN0AROFL
Linker Name
Mal-adipamide-Ala-Ala
Linker Type
Cathepsin-cleavable linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C18H26N4O7
Isosmiles
CC(NC(=O)C(C)NC(=O)CCCCC(=O)NCCN1C(=O)C=CC1=O)C(=O)O
InChI
InChI=1S/C18H26N4O7/c1-11(17(27)21-12(2)18(28)29)20-14(24)6-4-3-5-13(23)19-9-10-22-15(25)7-8-16(22)26/h7-8,11-12H,3-6,9-10H2,1-2H3,(H,19,23)(H,20,24)(H,21,27)(H,28,29)
InChIKey
CPKFQVOFDMYIRV-UHFFFAOYSA-N
Pharmaceutical Properties
Molecule Weight
410.427
Polar area
161.98
Complexity
410.1801492
xlogp Value
-1.318
Heavy Count
29
Rot Bonds
12
Hbond acc
6
Hbond Donor
4
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
TAK-164 [Phase 1 (Terminated)]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Patients Enrolled
GCC-positive (H-score10 as indicated by IHC) GI cancers for whom standard treatment was no longer effective, or not available, Eligible GI malignancies included, but were not limited to: metastatic colorectal carcinoma, gastric carcinoma, esophageal carcinoma, small intestine cancer, and pancreatic cancer.
Administration Dosage
TAK-164 as a single intravenous infusion with a duration of up to 2 h, on day 1 of each 21-day cycle or every 3 weeks, until disease progression, unacceptable toxicity, or withdrawal from the study. Doses of 0.004 mg/kg, 0.008 mg/kg, 0.016 mg/kg, 0.032 mg/kg, 0.064 mg/kg, 0.12 mg/kg, 0.16 mg/kg, 0.19 mg/kg, 0.25 mg/kg, and 0.32 mg/kg were planned. To guide dose escalation, a method based on a Bayesian model of modified toxicity probability interval (mTPI) was used.

   Click to Show/Hide
Related Clinical Trial
NCT Number NCT03449030  Clinical Status Phase 1
Clinical Description
An open-label, dose escalation, phase 1, first-in-human study of TAK-164, an antibody-drug conjugate, in patients with advanced gastrointestinal cancers expressing guanylyl cyclase C.
Primary Endpoint
Dosing was capped at 0.19 mg/kg due to hepatic toxicity. The RP2D was determined as 0.064 mg/kg but was considered insufficient to derive significant clinical benefit.
Other Endpoint
No pts had dose-limiting toxicities (DLT) in cycle 1 up to 0.32 mg/kg. TAK-164 appeared to have a manageable safety profile up to 0.064 mg/kg in pts with advanced GI cancers.
References
Ref 1 A phase I, first-in-human study of TAK-164, an antibody-drug conjugate, in patients with advanced gastrointestinal cancers expressing guanylyl cyclase C. Cancer Chemother Pharmacol. 2023 Apr;91(4):291-300.