Linker Information

General Information of This Linker

Linker ID	LIN0MVTCK
Linker Name	PEG2-Val-Cit-PABC
Linker Type	Cathepsin-cleavable linker
Antibody-Linker Relation	Cleavable
Structure
Structure	3D MOL		2D MOL
Formula	C22H28N4O6
Isosmiles	C[C@@H](C(=O)NC1=CC=C(C=C1)CO)NC(=O)[C@H](C(C)C)NC(=O)CCN2C(=O)C=CC2=O
PubChem CID	153352098
InChI	InChI=1S/C22H28N4O6/c1-13(2)20(25-17(28)10-11-26-18(29)8-9-19(26)30)22(32)23-14(3)21(31)24-16-6-4-15(12-27)5-7-16/h4-9,13-14,20,27H,10-12H2,1-3H3,(H,23,32)(H,24,31)(H,25,28)/t14-,20-/m0/s1
InChIKey	NSHZSEBCOJNZHE-XOBRGWDASA-N
IUPAC Name	(2S)-2-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]-N-[(2S)-1-[4-(hydroxymethyl)anilino]-1-oxopropan-2-yl]-3-methylbutanamide
Pharmaceutical Properties	Molecule Weight	444.5	Polar area	145
	Complexity	740	xlogp Value	-0.1
	Heavy Count	32	Rot Bonds	10
	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

Anti-FucGM1-46 ADC [Investigative]

ADC Info

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 2 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 61.24%	Positive FucGM1 expression (FucGM1+++/++)
Method Description	Female CB-17 SCID mice were each inoculated in the flank area with the 5 million tumor cells. To examine the efficacy of anti-FucGM1 ADC-45, mice were dosed with a single IP administration of 0.005 mol/kg.
In Vivo Model	H187 CDX model
In Vitro Model	Lung small cell carcinoma	NCI-H187 cells		CVCL_1501
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.58%	Positive FucGM1 expression (FucGM1+++/++)
Method Description	Female CB-17 SCID mice were each inoculated in the flank area with the 5 million tumor cells. To examine the efficacy of anti-FucGM1 ADC-45, mice were dosed with a single IP administration of 0.02 mol/kg.
In Vivo Model	H187 CDX model
In Vitro Model	Lung small cell carcinoma	NCI-H187 cells		CVCL_1501

Revealed Based on the Cell Line Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	2.20 nM	Positive FucGM1 expression (FucGM1+++/++)
Method Description	Cancer cell lines were incubated with compounds for 72 h. IC50 values were determined by quantitating viable cells using a CellTiter-Glo luminescent assay.
In Vitro Model	Lung small cell carcinoma	NCI-H187 cells		CVCL_1501

Anti-MSLN-46 ADC [Investigative]

ADC Info

Revealed Based on the Cell Line Data

Click To Hide/Show 2 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.02 nM	Positive MSLN expression (MSLN+++/++)
Method Description	Cancer cell lines were incubated with compounds for 72 h. IC50 values were determined by quantitating viable cells using a CellTiter-Glo luminescent assay.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 100 nM	Negative MSLN expression (MSLN-)
Method Description	Cancer cell lines were incubated with compounds for 72 h. IC50 values were determined by quantitating viable cells using a CellTiter-Glo luminescent assay.
In Vitro Model	Lung small cell carcinoma	NCI-H187 cells		CVCL_1501

References

Ref 1	Design, Synthesis, and Structure-Activity Relationships of Novel Tetrahydroisoquinolino Benzodiazepine Dimer Antitumor Agents and Their Application in Antibody-Drug Conjugates. J Med Chem. 2020 Nov 25;63(22):13913-13950. doi: 10.1021/acs.jmedchem.0c01385.