General Information of This Payload
Payload ID
PAY0QKTKM
Name
Duo5
Synonyms
Duo5
   Click to Show/Hide
Target Microtubule (MT)
Formula
C40H69N9O6
Isosmiles
CC([C@H](N(C)C)C(N[C@@H](C(C)C)C(N(C)[C@H]([C@H](OC)CC(N1CCC[C@H]1[C@H](OC)[C@H](C(N[C@H](CN=[N+]=[N-])CC2=CC=C(N)C=C2)=O)C)=O)[C@H](CC)C)=O)=O)C
InChI
InChI=1S/C40H69N9O6/c1-13-26(6)36(48(10)40(53)34(24(2)3)45-39(52)35(25(4)5)47(8)9)32(54-11)22-33(50)49-20-14-15-31(49)37(55-12)27(7)38(51)44-30(23-43-46-42)21-28-16-18-29(41)19-17-28/h16-19,24-27,30-32,34-37H,13-15,20-23,41H2,1-12H3,(H,44,51)(H,45,52)/t26-,27+,30-,31-,32+,34-,35-,36-,37+/m0/s1
InChIKey
QIHHTRNUHMRKQK-MNFMTBGBSA-N
Pharmaceutical Properties
Molecule Weight
772.049
Polar area
195.3
Complexity
1365.212769
xlogp Value
4.2537
Heavy Count
55
Rot Bonds
22
Hbond acc
9
Hbond Donor
3
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
alpha-cMET FDC-Duo5_P1 [Investigative]
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 Tumor Growth lnhibition value (TGl)
100%
Method Description
5 mg/kg
In Vivo Model Mouse SNU-5 xenograft model
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal inhibitory Concentration (lC50)
1.2-2.2 nM
High cMET expression (cMET +++)
Method Description
SNU-5 (1750 cells/well, 12.5 uL), A549 cells (750 cells/well, 12.5 uL), HT-29 (1000 cells/well, 12.5 uL) and SK-BR-3 (1000 cells/well, 12.5 uL) were seeded in a white flat-bottom 384-well plate (3570, Corning) at least 4-8 h before drug treatment for SNU-5 and 16-24 h for all the adherent cells. 2× working stock of the anti-cMET FDC (200 nM) or ADC (20-200 nM) were initially prepared in the cell growth media which were subsequently serially diluted in the corresponding media 3-fold. Following this, 12.5 uL of each of the serially diluted drug conjugates were added into the 384-well plate containing the cells. In a similar manner, replicates of 12.5 uL each of either a 2 uM Staurosporine (S1421, Selleck Chemicals) or media only was added into the wells to serve as the 100% cell killing and 0% cell killing, respectively. For the combination treatment, cells were treated with a 3-fold serial dilution of the anti-cMET IgG starting at 50 nM (final concentration in the well) while holding the FDC concentration constant at the approximate IC50 of 2 nM. After 96 h incubation at 37°C with 5% CO2, 25 uL of room temperature CellTiterGlo2.0 reagent (G9241, Promega) was added to each well using a multichannel pipette followed by a 2-min shaking using an orbital shaker (500 rpm), and then a 10-min incubation at room temperature. Afterwards, the plate was read using plate reader capable of reading luminescence in multi-well plates (Tecan Spark). Data were analyzed using GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Gastric adenocarcinoma SNU-5 cells CVCL_0078
alpha-cMET ADC-Duo5_P1 (hi DAR) [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)
0.2 nM
High cMET expression (cMET +++)
Method Description
SNU-5 (1750 cells/well, 12.5 uL), A549 cells (750 cells/well, 12.5 uL), HT-29 (1000 cells/well, 12.5 uL) and SK-BR-3 (1000 cells/well, 12.5 uL) were seeded in a white flat-bottom 384-well plate (3570, Corning) at least 4-8 h before drug treatment for SNU-5 and 16-24 h for all the adherent cells. 2× working stock of the anti-cMET FDC (200 nM) or ADC (20-200 nM) were initially prepared in the cell growth media which were subsequently serially diluted in the corresponding media 3-fold. Following this, 12.5 uL of each of the serially diluted drug conjugates were added into the 384-well plate containing the cells. In a similar manner, replicates of 12.5 uL each of either a 2 uM Staurosporine (S1421, Selleck Chemicals) or media only was added into the wells to serve as the 100% cell killing and 0% cell killing, respectively. For the combination treatment, cells were treated with a 3-fold serial dilution of the anti-cMET IgG starting at 50 nM (final concentration in the well) while holding the FDC concentration constant at the approximate IC50 of 2 nM. After 96 h incubation at 37°C with 5% CO2, 25 uL of room temperature CellTiterGlo2.0 reagent (G9241, Promega) was added to each well using a multichannel pipette followed by a 2-min shaking using an orbital shaker (500 rpm), and then a 10-min incubation at room temperature. Afterwards, the plate was read using plate reader capable of reading luminescence in multi-well plates (Tecan Spark). Data were analyzed using GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Gastric adenocarcinoma SNU-5 cells CVCL_0078
alpha-cMET FDC-Duo5_P2 [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)
1.8 nM
High cMET expression (cMET +++)
Method Description
SNU-5 (1750 cells/well, 12.5 uL), A549 cells (750 cells/well, 12.5 uL), HT-29 (1000 cells/well, 12.5 uL) and SK-BR-3 (1000 cells/well, 12.5 uL) were seeded in a white flat-bottom 384-well plate (3570, Corning) at least 4-8 h before drug treatment for SNU-5 and 16-24 h for all the adherent cells. 2× working stock of the anti-cMET FDC (200 nM) or ADC (20-200 nM) were initially prepared in the cell growth media which were subsequently serially diluted in the corresponding media 3-fold. Following this, 12.5 uL of each of the serially diluted drug conjugates were added into the 384-well plate containing the cells. In a similar manner, replicates of 12.5 uL each of either a 2 uM Staurosporine (S1421, Selleck Chemicals) or media only was added into the wells to serve as the 100% cell killing and 0% cell killing, respectively. For the combination treatment, cells were treated with a 3-fold serial dilution of the anti-cMET IgG starting at 50 nM (final concentration in the well) while holding the FDC concentration constant at the approximate IC50 of 2 nM. After 96 h incubation at 37°C with 5% CO2, 25 uL of room temperature CellTiterGlo2.0 reagent (G9241, Promega) was added to each well using a multichannel pipette followed by a 2-min shaking using an orbital shaker (500 rpm), and then a 10-min incubation at room temperature. Afterwards, the plate was read using plate reader capable of reading luminescence in multi-well plates (Tecan Spark). Data were analyzed using GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Gastric adenocarcinoma SNU-5 cells CVCL_0078
alpha-cMET FDC-Duo5_C [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)
2.8 nM
High cMET expression (cMET +++)
Method Description
SNU-5 (1750 cells/well, 12.5 uL), A549 cells (750 cells/well, 12.5 uL), HT-29 (1000 cells/well, 12.5 uL) and SK-BR-3 (1000 cells/well, 12.5 uL) were seeded in a white flat-bottom 384-well plate (3570, Corning) at least 4-8 h before drug treatment for SNU-5 and 16-24 h for all the adherent cells. 2× working stock of the anti-cMET FDC (200 nM) or ADC (20-200 nM) were initially prepared in the cell growth media which were subsequently serially diluted in the corresponding media 3-fold. Following this, 12.5 uL of each of the serially diluted drug conjugates were added into the 384-well plate containing the cells. In a similar manner, replicates of 12.5 uL each of either a 2 uM Staurosporine (S1421, Selleck Chemicals) or media only was added into the wells to serve as the 100% cell killing and 0% cell killing, respectively. For the combination treatment, cells were treated with a 3-fold serial dilution of the anti-cMET IgG starting at 50 nM (final concentration in the well) while holding the FDC concentration constant at the approximate IC50 of 2 nM. After 96 h incubation at 37°C with 5% CO2, 25 uL of room temperature CellTiterGlo2.0 reagent (G9241, Promega) was added to each well using a multichannel pipette followed by a 2-min shaking using an orbital shaker (500 rpm), and then a 10-min incubation at room temperature. Afterwards, the plate was read using plate reader capable of reading luminescence in multi-well plates (Tecan Spark). Data were analyzed using GraphPad Prism software.

   Click to Show/Hide
In Vitro Model Gastric adenocarcinoma SNU-5 cells CVCL_0078
References
Ref 1 Discovery of novel cMET-targeting antibody Fab drug conjugates as potential treatment for solid tumors with highly expressed cMET