Linker Information

General Information of This Linker
Linker ID
LIN0IISSJ
Linker Name
Ala-Ala dipeptide
Linker Type
Flexible reactive (amino) linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C6H12N2O3
Isosmiles
C[C@@H](C(=O)N[C@@H](C)C(=O)O)N
PubChem CID
5484352
InChI
InChI=1S/C6H12N2O3/c1-3(7)5(9)8-4(2)6(10)11/h3-4H,7H2,1-2H3,(H,8,9)(H,10,11)/t3-,4-/m0/s1
InChIKey
DEFJQIDDEAULHB-IMJSIDKUSA-N
IUPAC Name
(2S)-2-[[(2S)-2-aminopropanoyl]amino]propanoic acid
Pharmaceutical Properties
Molecule Weight
160.17
Polar area
92.4
Complexity
169
xlogp Value
-3.3
Heavy Count
11
Rot Bonds
3
Hbond acc
4
Hbond Donor
3
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Anti-FOLR1-Ala-Ala-IGN [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 35) Positive FOLR1 expression (FOLR1+++/++)
Method Description
Animals with established tumors were randomized into six mice per treatment group and dosed with a single i.v. dose of vehicle or IGN ADCs at either 3 ug/kg drug dose.
In Vivo Model NCI-H2110 CDX model
In Vitro Model Lung non-small cell carcinoma NCI-H2110 cells CVCL_1530
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50)
5.00 pM
Positive EGFR expression (EGFR+++/++)
Method Description
Cells were incubated with a serial dilution of conjugate, and a mixture of conjugate and excess, unconjugated anti-EGFR (0.35 M) or anti-FR antibody (1 M), respectively (blocking). After 4 days of continuous treatment with conjugates, cell viability was determined using Cell Titer Glo reagent.
In Vitro Model Human papillomavirus-related endocervical adenocarcinoma KB cells CVCL_0372
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50)
9.30 pM
Positive EGFR expression (EGFR+++/++)
Method Description
Cells were incubated with a serial dilution of conjugate, and a mixture of conjugate and excess, unconjugated anti-EGFR (0.35 M) or anti-FR antibody (1 M), respectively (blocking). After 4 days of continuous treatment with conjugates, cell viability was determined using Cell Titer Glo reagent.
In Vitro Model Ovarian endometrioid adenocarcinoma IGROV-1 cells CVCL_1304
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50)
30.00 pM
Positive EGFR expression (EGFR+++/++)
Method Description
Cells were incubated with a serial dilution of conjugate, and a mixture of conjugate and excess, unconjugated anti-EGFR (0.35 M) or anti-FR antibody (1 M), respectively (blocking). After 4 days of continuous treatment with conjugates, cell viability was determined using Cell Titer Glo reagent.
In Vitro Model Invasive breast carcinoma T-47D cells CVCL_0553
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50)
30.00 pM
Positive EGFR expression (EGFR+++/++)
Method Description
Cells were incubated with a serial dilution of conjugate, and a mixture of conjugate and excess, unconjugated anti-EGFR (0.35 M) or anti-FR antibody (1 M), respectively (blocking). After 4 days of continuous treatment with conjugates, cell viability was determined using Cell Titer Glo reagent.
In Vitro Model Ovarian adenocarcinoma OV-90 cells CVCL_3768
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50)
0.20 nM
Positive EGFR expression (EGFR+++/++)
Method Description
Cells were incubated with a serial dilution of conjugate, and a mixture of conjugate and excess, unconjugated anti-EGFR (0.35 M) or anti-FR antibody (1 M), respectively (blocking). After 4 days of continuous treatment with conjugates, cell viability was determined using Cell Titer Glo reagent.
In Vitro Model Lung non-small cell carcinoma NCI-H2110 cells CVCL_1530
Anti-EGFR-Ala-Ala-IGN [Investigative]
 ADC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50)
6.10 pM
Positive EGFR expression (EGFR+++/++)
Method Description
Cells were incubated with a serial dilution of conjugate, and a mixture of conjugate and excess, unconjugated anti-EGFR (0.35 M) or anti-FR antibody (1 M), respectively (blocking). After 4 days of continuous treatment with conjugates, cell viability was determined using Cell Titer Glo reagent.
In Vitro Model Tongue squamous cell carcinoma SAS cells CVCL_1675
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50)
7.50 pM
Positive EGFR expression (EGFR+++/++)
Method Description
Cells were incubated with a serial dilution of conjugate, and a mixture of conjugate and excess, unconjugated anti-EGFR (0.35 M) or anti-FR antibody (1 M), respectively (blocking). After 4 days of continuous treatment with conjugates, cell viability was determined using Cell Titer Glo reagent.
In Vitro Model Oral cavity squamous cell carcinoma HSC-2 cells CVCL_1287
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50)
11.00 pM
Positive EGFR expression (EGFR+++/++)
Method Description
Cells were incubated with a serial dilution of conjugate, and a mixture of conjugate and excess, unconjugated anti-EGFR (0.35 M) or anti-FR antibody (1 M), respectively (blocking). After 4 days of continuous treatment with conjugates, cell viability was determined using Cell Titer Glo reagent.
In Vitro Model Lung mucoepidermoid carcinoma NCI-H292 cells CVCL_0455
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50)
17.00 pM
Positive EGFR expression (EGFR+++/++)
Method Description
Cells were incubated with a serial dilution of conjugate, and a mixture of conjugate and excess, unconjugated anti-EGFR (0.35 M) or anti-FR antibody (1 M), respectively (blocking). After 4 days of continuous treatment with conjugates, cell viability was determined using Cell Titer Glo reagent.
In Vitro Model Lung adenocarcinoma PC-9 cells CVCL_B260
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50)
45.00 pM
Positive EGFR expression (EGFR+++/++)
Method Description
Cells were incubated with a serial dilution of conjugate, and a mixture of conjugate and excess, unconjugated anti-EGFR (0.35 M) or anti-FR antibody (1 M), respectively (blocking). After 4 days of continuous treatment with conjugates, cell viability was determined using Cell Titer Glo reagent.
In Vitro Model Pancreatic ductal adenocarcinoma BxPC-3 cells CVCL_0186
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Effective Concentration (EC50)
93.00 pM
Positive EGFR expression (EGFR+++/++)
Method Description
Cells were incubated with a serial dilution of conjugate, and a mixture of conjugate and excess, unconjugated anti-EGFR (0.35 M) or anti-FR antibody (1 M), respectively (blocking). After 4 days of continuous treatment with conjugates, cell viability was determined using Cell Titer Glo reagent.
In Vitro Model Lung adenocarcinoma NCI-H1975 cells CVCL_1511
References
Ref 1 Optimizing Lysosomal Activation of Antibody-Drug Conjugates (ADCs) by Incorporation of Novel Cleavable Dipeptide Linkers. Mol Pharm. 2019 Dec 2;16(12):4817-4825. doi: 10.1021/acs.molpharmaceut.9b00696. Epub 2019 Oct 29.

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