General Information of This Linker
Linker ID
LIN0HITPJ
Linker Name
US20240269308A1 aHer2- (AL6-LP1)n Linker
Linker Type
Unclear
Antibody-Linker Relation
Unclear
Structure
Formula
C39H62N6O11
Isosmiles
CC([C@H](NC(CCOCCOCCOCCOCCNC(COC1C#CCCCCC1)=O)=O)C(N[C@@H](CCCNC(N)=O)C(NC2=CC=C(C=C2)CO)=O)=O)C
InChI
InChI=1S/C39H62N6O11/c1-29(2)36(38(50)44-33(11-8-17-42-39(40)51)37(49)43-31-14-12-30(27-46)13-15-31)45-34(47)16-19-52-21-23-54-25-26-55-24-22-53-20-18-41-35(48)28-56-32-9-6-4-3-5-7-10-32/h12-15,29,32-33,36,46H,3-6,8-9,11,16-28H2,1-2H3,(H,41,48)(H,43,49)(H,44,50)(H,45,47)(H3,40,42,51)/t32?,33-,36-/m0/s1
InChIKey
MMSOPIGULODHOZ-OREWIGCKSA-N
Pharmaceutical Properties
Molecule Weight
790.956
Polar area
237.9
Complexity
1303.720796
xlogp Value
1.1169
Heavy Count
56
Rot Bonds
29
Hbond acc
11
Hbond Donor
7
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
aHer2- (AL7-LP1)n [Investigative]
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 (lC50)
0.114 nM
High HER2 expression (HER2 +++)
Method Description
The cell line used in the anti-proliferation assays was SK-BR-3, a human breast, adenocarcinoma (pleural effusion) cell line; The cells were grown in McCoy's 5a Medium+10% FBS. To run the assay, the cells (80 ul, 1000 cells) were added to each well in a 96-well plate and incubated for 24 hours at 37°C. with CO,. Next, the cells were treated with test compounds (20 ul) at various concentrations in appropriate cell culture medium (total volume, 0.1 mL). The control wells contain cells and the medium but lack the test compounds. The plates were incubated for 144 hours at 37°C. with CO,. CTG reagent was then added to the wells (100 il). After the plates were shaken for 10 min and then incubated for 10 min at room temperature, paste the clear bottom with white back seal and record luminescence with Envision. The inhibition % was calculated according to the following equation: inhibition %=[1- (assay-blank)/ (control-blank)|x100.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
aHer2- (AL11a-LP1)n [Investigative]
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 (lC50)
0.152 nM
High HER2 expression (HER2 +++)
Method Description
The cell line used in the anti-proliferation assays was SK-BR-3, a human breast, adenocarcinoma (pleural effusion) cell line; The cells were grown in McCoy's 5a Medium+10% FBS. To run the assay, the cells (80 ul, 1000 cells) were added to each well in a 96-well plate and incubated for 24 hours at 37°C. with CO,. Next, the cells were treated with test compounds (20 ul) at various concentrations in appropriate cell culture medium (total volume, 0.1 mL). The control wells contain cells and the medium but lack the test compounds. The plates were incubated for 144 hours at 37°C. with CO,. CTG reagent was then added to the wells (100 il). After the plates were shaken for 10 min and then incubated for 10 min at room temperature, paste the clear bottom with white back seal and record luminescence with Envision. The inhibition % was calculated according to the following equation: inhibition %=[1- (assay-blank)/ (control-blank)|x100.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
aHer2- (BL1-LP1)n [Investigative]
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 (lC50)
0.16 nM
High HER2 expression (HER2 +++)
Method Description
The cell line used in the anti-proliferation assays was SK-BR-3, a human breast, adenocarcinoma (pleural effusion) cell line; The cells were grown in McCoy's 5a Medium+10% FBS. To run the assay, the cells (80 ul, 1000 cells) were added to each well in a 96-well plate and incubated for 24 hours at 37°C. with CO,. Next, the cells were treated with test compounds (20 ul) at various concentrations in appropriate cell culture medium (total volume, 0.1 mL). The control wells contain cells and the medium but lack the test compounds. The plates were incubated for 144 hours at 37°C. with CO,. CTG reagent was then added to the wells (100 il). After the plates were shaken for 10 min and then incubated for 10 min at room temperature, paste the clear bottom with white back seal and record luminescence with Envision. The inhibition % was calculated according to the following equation: inhibition %=[1- (assay-blank)/ (control-blank)|x100.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
aHer2- (AL7-LP2)n [Investigative]
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 (lC50)
0.164 nM
High HER2 expression (HER2 +++)
Method Description
The cell line used in the anti-proliferation assays was SK-BR-3, a human breast, adenocarcinoma (pleural effusion) cell line; The cells were grown in McCoy's 5a Medium+10% FBS. To run the assay, the cells (80 ul, 1000 cells) were added to each well in a 96-well plate and incubated for 24 hours at 37°C. with CO,. Next, the cells were treated with test compounds (20 ul) at various concentrations in appropriate cell culture medium (total volume, 0.1 mL). The control wells contain cells and the medium but lack the test compounds. The plates were incubated for 144 hours at 37°C. with CO,. CTG reagent was then added to the wells (100 il). After the plates were shaken for 10 min and then incubated for 10 min at room temperature, paste the clear bottom with white back seal and record luminescence with Envision. The inhibition % was calculated according to the following equation: inhibition %=[1- (assay-blank)/ (control-blank)|x100.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
aHer2- (AL7-LP3)n [Investigative]
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 (lC50)
0.172 nM
High HER2 expression (HER2 +++)
Method Description
The cell line used in the anti-proliferation assays was SK-BR-3, a human breast, adenocarcinoma (pleural effusion) cell line; The cells were grown in McCoy's 5a Medium+10% FBS. To run the assay, the cells (80 ul, 1000 cells) were added to each well in a 96-well plate and incubated for 24 hours at 37°C. with CO,. Next, the cells were treated with test compounds (20 ul) at various concentrations in appropriate cell culture medium (total volume, 0.1 mL). The control wells contain cells and the medium but lack the test compounds. The plates were incubated for 144 hours at 37°C. with CO,. CTG reagent was then added to the wells (100 il). After the plates were shaken for 10 min and then incubated for 10 min at room temperature, paste the clear bottom with white back seal and record luminescence with Envision. The inhibition % was calculated according to the following equation: inhibition %=[1- (assay-blank)/ (control-blank)|x100.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
aHer2- (AL7-LP4)n [Investigative]
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 (lC50)
0.186 nM
High HER2 expression (HER2 +++)
Method Description
The cell line used in the anti-proliferation assays was SK-BR-3, a human breast, adenocarcinoma (pleural effusion) cell line; The cells were grown in McCoy's 5a Medium+10% FBS. To run the assay, the cells (80 ul, 1000 cells) were added to each well in a 96-well plate and incubated for 24 hours at 37°C. with CO,. Next, the cells were treated with test compounds (20 ul) at various concentrations in appropriate cell culture medium (total volume, 0.1 mL). The control wells contain cells and the medium but lack the test compounds. The plates were incubated for 144 hours at 37°C. with CO,. CTG reagent was then added to the wells (100 il). After the plates were shaken for 10 min and then incubated for 10 min at room temperature, paste the clear bottom with white back seal and record luminescence with Envision. The inhibition % was calculated according to the following equation: inhibition %=[1- (assay-blank)/ (control-blank)|x100.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
aHer2- (AL7-LP7)n [Investigative]
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 (lC50)
0.303 nM
High HER2 expression (HER2 +++)
Method Description
The cell line used in the anti-proliferation assays was SK-BR-3, a human breast, adenocarcinoma (pleural effusion) cell line; The cells were grown in McCoy's 5a Medium+10% FBS. To run the assay, the cells (80 ul, 1000 cells) were added to each well in a 96-well plate and incubated for 24 hours at 37°C. with CO,. Next, the cells were treated with test compounds (20 ul) at various concentrations in appropriate cell culture medium (total volume, 0.1 mL). The control wells contain cells and the medium but lack the test compounds. The plates were incubated for 144 hours at 37°C. with CO,. CTG reagent was then added to the wells (100 il). After the plates were shaken for 10 min and then incubated for 10 min at room temperature, paste the clear bottom with white back seal and record luminescence with Envision. The inhibition % was calculated according to the following equation: inhibition %=[1- (assay-blank)/ (control-blank)|x100.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
FeID1- (AL7-LP2)n [Investigative]
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 (lC50)
47.8 nM
Low ID1 expression (ID1+)
Method Description
The cell line used in the anti-proliferation assays was SK-BR-3, a human breast, adenocarcinoma (pleural effusion) cell line; The cells were grown in McCoy's 5a Medium+10% FBS. To run the assay, the cells (80 ul, 1000 cells) were added to each well in a 96-well plate and incubated for 24 hours at 37°C. with CO,. Next, the cells were treated with test compounds (20 ul) at various concentrations in appropriate cell culture medium (total volume, 0.1 mL). The control wells contain cells and the medium but lack the test compounds. The plates were incubated for 144 hours at 37°C. with CO,. CTG reagent was then added to the wells (100 il). After the plates were shaken for 10 min and then incubated for 10 min at room temperature, paste the clear bottom with white back seal and record luminescence with Envision. The inhibition % was calculated according to the following equation: inhibition %=[1- (assay-blank)/ (control-blank)|x100.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
FeID1- (BL1-LP1)n [Investigative]
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 (lC50)
89.1 nM
Low ID1 expression (ID1+)
Method Description
The cell line used in the anti-proliferation assays was SK-BR-3, a human breast, adenocarcinoma (pleural effusion) cell line; The cells were grown in McCoy's 5a Medium+10% FBS. To run the assay, the cells (80 ul, 1000 cells) were added to each well in a 96-well plate and incubated for 24 hours at 37°C. with CO,. Next, the cells were treated with test compounds (20 ul) at various concentrations in appropriate cell culture medium (total volume, 0.1 mL). The control wells contain cells and the medium but lack the test compounds. The plates were incubated for 144 hours at 37°C. with CO,. CTG reagent was then added to the wells (100 il). After the plates were shaken for 10 min and then incubated for 10 min at room temperature, paste the clear bottom with white back seal and record luminescence with Envision. The inhibition % was calculated according to the following equation: inhibition %=[1- (assay-blank)/ (control-blank)|x100.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
FeID1- (AL7-LP3)n [Investigative]
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 (lC50)
121 nM
Low ID1 expression (ID1+)
Method Description
The cell line used in the anti-proliferation assays was SK-BR-3, a human breast, adenocarcinoma (pleural effusion) cell line; The cells were grown in McCoy's 5a Medium+10% FBS. To run the assay, the cells (80 ul, 1000 cells) were added to each well in a 96-well plate and incubated for 24 hours at 37°C. with CO,. Next, the cells were treated with test compounds (20 ul) at various concentrations in appropriate cell culture medium (total volume, 0.1 mL). The control wells contain cells and the medium but lack the test compounds. The plates were incubated for 144 hours at 37°C. with CO,. CTG reagent was then added to the wells (100 il). After the plates were shaken for 10 min and then incubated for 10 min at room temperature, paste the clear bottom with white back seal and record luminescence with Envision. The inhibition % was calculated according to the following equation: inhibition %=[1- (assay-blank)/ (control-blank)|x100.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
FeID1- (AL7-LP1)n [Investigative]
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 (lC50)
156 nM
Low ID1 expression (ID1+)
Method Description
The cell line used in the anti-proliferation assays was SK-BR-3, a human breast, adenocarcinoma (pleural effusion) cell line; The cells were grown in McCoy's 5a Medium+10% FBS. To run the assay, the cells (80 ul, 1000 cells) were added to each well in a 96-well plate and incubated for 24 hours at 37°C. with CO,. Next, the cells were treated with test compounds (20 ul) at various concentrations in appropriate cell culture medium (total volume, 0.1 mL). The control wells contain cells and the medium but lack the test compounds. The plates were incubated for 144 hours at 37°C. with CO,. CTG reagent was then added to the wells (100 il). After the plates were shaken for 10 min and then incubated for 10 min at room temperature, paste the clear bottom with white back seal and record luminescence with Envision. The inhibition % was calculated according to the following equation: inhibition %=[1- (assay-blank)/ (control-blank)|x100.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
FeID1- (AL7-LP4)n [Investigative]
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 (lC50)
212 nM
Low ID1 expression (ID1+)
Method Description
The cell line used in the anti-proliferation assays was SK-BR-3, a human breast, adenocarcinoma (pleural effusion) cell line; The cells were grown in McCoy's 5a Medium+10% FBS. To run the assay, the cells (80 ul, 1000 cells) were added to each well in a 96-well plate and incubated for 24 hours at 37°C. with CO,. Next, the cells were treated with test compounds (20 ul) at various concentrations in appropriate cell culture medium (total volume, 0.1 mL). The control wells contain cells and the medium but lack the test compounds. The plates were incubated for 144 hours at 37°C. with CO,. CTG reagent was then added to the wells (100 il). After the plates were shaken for 10 min and then incubated for 10 min at room temperature, paste the clear bottom with white back seal and record luminescence with Envision. The inhibition % was calculated according to the following equation: inhibition %=[1- (assay-blank)/ (control-blank)|x100.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
FeID1- (AL11a-LP1)n [Investigative]
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 (lC50) > 400 nM Low ID1 expression (ID1+)
Method Description
The cell line used in the anti-proliferation assays was SK-BR-3, a human breast, adenocarcinoma (pleural effusion) cell line; The cells were grown in McCoy's 5a Medium+10% FBS. To run the assay, the cells (80 ul, 1000 cells) were added to each well in a 96-well plate and incubated for 24 hours at 37°C. with CO,. Next, the cells were treated with test compounds (20 ul) at various concentrations in appropriate cell culture medium (total volume, 0.1 mL). The control wells contain cells and the medium but lack the test compounds. The plates were incubated for 144 hours at 37°C. with CO,. CTG reagent was then added to the wells (100 il). After the plates were shaken for 10 min and then incubated for 10 min at room temperature, paste the clear bottom with white back seal and record luminescence with Envision. The inhibition % was calculated according to the following equation: inhibition %=[1- (assay-blank)/ (control-blank)|x100.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
References
Ref 1 Prodrugs of topoisomerase I inhibitor for ADC conjugations and methods of use thereof