Linker Information

General Information of This Linker
Linker ID
LIN0KCWDR
Linker Name
Mal-PEG2Val-Cit-PAB-OH
Linker Type
Cathepsin-cleavable linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C29H42N6O9
Isosmiles
CC(C)C(C(=O)N(C1=CC=C(C=C1)CO)C(CCCNC(=O)N)C(=O)N)NC(=O)CCOCCOCCN2C(=O)C=CC2=O
PubChem CID
155889591
InChI
InChI=1S/C29H42N6O9/c1-19(2)26(33-23(37)11-14-43-16-17-44-15-13-34-24(38)9-10-25(34)39)28(41)35(21-7-5-20(18-36)6-8-21)22(27(30)40)4-3-12-32-29(31)42/h5-10,19,22,26,36H,3-4,11-18H2,1-2H3,(H2,30,40)(H,33,37)(H3,31,32,42)
InChIKey
FUIUTNYVVFCDIA-UHFFFAOYSA-N
IUPAC Name
5-(carbamoylamino)-2-[N-[2-[3-[2-[2-(2,5-dioxopyrrol-1-yl)ethoxy]ethoxy]propanoylamino]-3-methylbutanoyl]-4-(hydroxymethyl)anilino]pentanamide
Pharmaceutical Properties
Molecule Weight
618.7
Polar area
224
Complexity
1010
xlogp Value
-1.6
Heavy Count
44
Rot Bonds
20
Hbond acc
9
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
Farletuzumab ecteribulin [Phase 2]
 ADC Info 
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 2.10% (Day 60) Moderate FOLR1 expression (FOLR1++)
Method Description
The each group was randomized to be a similar mean volume of 100-250 mm3.The treatment schedule was as follows: a single IV injection of vehicle at day 0, and a single IV injection of MORAb-202 at 2.5 mg/kg at day 0 ((Q1Dx1) or every 11 days (Q11Dx2)).
In Vivo Model Breast cancer PDX model (PDX: OD-BRE-0631)
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 65.70% (Day 60) Moderate FOLR1 expression (FOLR1++)
Method Description
The each group was randomized to be a similar mean volume of 100-250 mm3.The treatment schedule was as follows: a single IV injection of vehicle at day 0, and a single IV injection of MORAb-202 at 5 mg/kg at day 0 ((Q1Dx1) or every 11 days (Q11Dx2)).
In Vivo Model Breast cancer PDX model (PDX: OD-BRE-0631)
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.30% (Day 60) High FOLR1 expression (FOLR1+++)
Method Description
The each group was randomized to be a similar mean volume of 100-250 mm3.The treatment schedule was as follows: a single IV injection of vehicle at day 0, and a single IV injection of MORAb-202 at 5 mg/kg at day 0 ((Q1Dx1) or every 11 days (Q11Dx2)).
In Vivo Model Breast cancer PDX model (PDX: IM-BRE-563)
Revealed Based on the Cell Line Data
Click To Hide/Show 17 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.01 pM
High FOLR1 expression (FOLR1+++)
Method Description
Threefold serial dilutions of MORAb-202 (5.1x1012 - 1.0x107 mol/L) were added to the cell lines, and the cells were cultured for 5 days. Cells were stained with 0.2% crystal violet solution, a triarylmethane dye which accumulates in the nucleus of viable cells, washed with water, and solubilized with 1% sodium dodecyl sulfate. The viable cell number was determined by measuring the optical density (OD 570 nm) of the resulting lysate.

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In Vitro Model Ovarian endometrioid adenocarcinoma IGROV-1 cells CVCL_1304
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.74 pM
High FOLR1 expression (FOLR1+++)
Method Description
Threefold serial dilutions of MORAb-202 (5.1x1012 - 1.0x107 mol/L) were added to the cell lines, and the cells were cultured for 5 days. Cells were stained with 0.2% crystal violet solution, a triarylmethane dye which accumulates in the nucleus of viable cells, washed with water, and solubilized with 1% sodium dodecyl sulfate. The viable cell number was determined by measuring the optical density (OD 570 nm) of the resulting lysate.

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In Vitro Model Lung non-small cell carcinoma NCI-H2110 cells CVCL_1530
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 1.00 pM Negative FOLR1 expression (FOLR1-)
Method Description
Threefold serial dilutions of MORAb-202 (5.1x1012 - 1.0x107 mol/L) were added to the cell lines, and the cells were cultured for 5 days. Cells were stained with 0.2% crystal violet solution, a triarylmethane dye which accumulates in the nucleus of viable cells, washed with water, and solubilized with 1% sodium dodecyl sulfate. The viable cell number was determined by measuring the optical density (OD 570 nm) of the resulting lysate.

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In Vitro Model Osteosarcoma SJSA-1 cells CVCL_1697
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
23.00 pM
Moderate FOLR1 expression (FOLR1++)
Method Description
Threefold serial dilutions of MORAb-202 (5.1x1012 - 1.0x107 mol/L) were added to the cell lines, and the cells were cultured for 5 days. Cells were stained with 0.2% crystal violet solution, a triarylmethane dye which accumulates in the nucleus of viable cells, washed with water, and solubilized with 1% sodium dodecyl sulfate. The viable cell number was determined by measuring the optical density (OD 570 nm) of the resulting lysate.

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In Vitro Model Skin squamous cell carcinoma A431-A3 cells CVCL_0037
Experiment 5 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.02 nM
High FOLR1 expression(FOLR1+++)
Method Description
Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model Ovarian endometrioid adenocarcinoma IGROV-1 cells CVCL_1304
Experiment 6 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.42 nM
Moderate FOLR1 expression(FOLR1++)
Method Description
Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model Lung non-small cell carcinoma NCI-H2110 cells CVCL_1530
Experiment 7 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.43 nM
Moderate FOLR1 expression(FOLR1++)
Method Description
Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model Ovarian serous adenocarcinoma Caov-3 cells CVCL_0201
Experiment 8 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.75 nM
Moderate FOLR1 expression(FOLR1++)
Method Description
Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Experiment 9 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.03 nM
Low FOLR1 expression(FOLR1+)
Method Description
Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model Endometrial adenocarcinoma HEC-59 cells CVCL_2930
Experiment 10 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.42 nM
Low FOLR1 expression(FOLR1+)
Method Description
Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model Breast ductal carcinoma HCC1954 cells CVCL_1259
Experiment 11 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.76 nM
Moderate FOLR1 expression(FOLR1++)
Method Description
Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model Gastric tubular adenocarcinoma MKN74 cells CVCL_2791
Experiment 12 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.81 nM
Moderate FOLR1 expression(FOLR1++)
Method Description
Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model Endometrial adenocarcinoma HEC-1-A cells CVCL_0293
Experiment 13 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
2.17 nM
Moderate FOLR1 expression(FOLR1++)
Method Description
Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model Gastric tubular adenocarcinoma MKN7 cells CVCL_1417
Experiment 14 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
4.42 nM
Low FOLR1 expression(FOLR1+)
Method Description
Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 15 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
13.15 nM
Moderate FOLR1 expression(FOLR1++)
Method Description
Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model Endometrial carcinoma HEC-251 cells CVCL_2927
Experiment 16 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
24.58 nM
Low FOLR1 expression(FOLR1+)
Method Description
Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model Gastric carcinoma NUGC-3 cells CVCL_1612
Experiment 17 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 100 nM Negative FOLR1 expression(FOLR1-)
Method Description
Cells were sub-cultured and seeded at 5,000 cells/well in complete growth medium in 96-well tissue culture plates, and incubated at 37°C, 5% CO2 overnight. Test reagents were serially diluted and added to the cell plates (initial concentration of 100 nM). Plates were incubated at 37°C, 5% CO2 for an additional 3 d.
In Vitro Model Skin squamous cell carcinoma A431 cells CVCL_0037
References
Ref 1 Antibody-drug conjugate MORAb-202 exhibits long-lasting antitumor efficacy in TNBC PDx models. Cancer Sci. 2021 Jun;112(6):2467-2480.
Ref 2 MORAb-202, an Antibody-Drug Conjugate Utilizing Humanized Anti-human FR Farletuzumab and the Microtubule-targeting Agent Eribulin, has Potent Antitumor Activity. Mol Cancer Ther. 2018 Dec;17(12):2665-2675. doi: 10.1158/1535-7163.MCT-17-1215. Epub 2018 Sep 27.

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