Linker Information
General Information of This Linker
| Linker ID |
LIN0PAMKQ
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| Linker Name |
BR112024020733A2 ADC2 Linker
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| Linker Type |
Beta-glucuronide based linker
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| Antibody-Linker Relation |
Cleavable
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| Structure |
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| Formula |
C73H102N6O31P2
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| Isosmiles |
C=C(CN1C(C2=CC(OC)=C(OCCCCCOC3=C(OC)C=C(C4=O)C(NC(O)[C@]5([H])CC(CN54)=C)=C3)C=C2N6C(OCC7=CC=C(O[C@H]8[C@H](O)[C@@H](O)[C@H](O)[C@H](O8)C(O)=O)C(C(NCCOCCOCCOCCOCCOCCO/N=C(CC/C(C)=C/CC/C(C)=C/COP(O)(OP(O)(O)=O)=O)\C)=O)=C7)=O)=O)C[C@@]1([H])C6O
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| InChI |
InChI=1S/C73H102N6O31P2/c1-44(12-11-13-45(2)18-22-107-112(94,95)110-111(91,92)93)14-15-48(5)76-106-33-32-102-31-30-101-29-28-100-27-26-99-25-24-98-23-19-74-66(83)52-36-49(16-17-57(52)108-72-64(82)62(80)63(81)65(109-72)71(88)89)43-105-73(90)79-54-40-61(59(97-7)38-51(54)69(86)78-42-47(4)35-56(78)70(79)87)104-21-10-8-9-20-103-60-39-53-50(37-58(60)96-6)68(85)77-41-46(3)34-55(77)67(84)75-53/h12,16-18,36-40,55-56,62-65,67,70,72,75,80-82,84,87H,3-4,8-11,13-15,19-35,41-43H2,1-2,5-7H3,(H,74,83)(H,88,89)(H,94,95)(H2,91,92,93)/b44-12+,45-18+,76-48+/t55-,56-,62-,63-,64+,65-,67?,70?,72+/m0/s1
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| InChIKey |
HVSVRFICKMBDSB-IYMCKXSPSA-N
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| Pharmaceutical Properties |
Molecule Weight
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1621.578
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Polar area
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486.15
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Complexity
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3791.275886
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xlogp Value
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5.248
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Heavy Count
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112
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Rot Bonds
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46
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Hbond acc
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29
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Hbond Donor
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11
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Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
BR112024020733A2ADC2 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | half-maximal cytotoxicity Concentration (CC50) |
0.148 nM
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High TROP2 expression (TROP2 +++) | ||
| Method Description |
Specifically, human pancreatic cancer cell lines (BxPC - 3, Capan - 1 and PATU - 8988s), breast cancer cell lines (JIMT - 1 and MDA - MB - 468), gastric cancer cell lines (NCI - N87, SNU - 601 and SNU - 620), colon cancer cell lines (HCT15, HT29, DLD - 1, SW480 and COLO205), ovarian cancer cell lines (OVCAR - 3), prostate cancer cell lines (PC - 3 and LNCaP) and Non small cell lung cancer cell lines (NCI - H1781, HCC827, Calu - 1 and Calu - 3). Use MMAE in standalone drug form and SG2057 (cAS #: 260417-62-7, MedKooBiosciences) as PBD dimer included in the ADC prepared according to Example 3. Inoculate each cancer cell line from 500 cells/well to 5000 cells/well into a 96 well plate and culture for 24 hours, followed by treatment with concentrations ranging from 0.256pM to 100nM (5-fold continuous dilution) of ADC1, ADC2, and ADC3 produced according to Example 3, as well as individual drugs MMAE and SG2057. After 144 hours, the number of live cells was quantified using sulforhodamine B (SRB) dye or Cell titrer glo.
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| 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 cytotoxicity Concentration (CC50) |
0.58 nM
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High TROP2 expression (TROP2 +++) | ||
| Method Description |
Specifically, human pancreatic cancer cell lines (BxPC - 3, Capan - 1 and PATU - 8988s), breast cancer cell lines (JIMT - 1 and MDA - MB - 468), gastric cancer cell lines (NCI - N87, SNU - 601 and SNU - 620), colon cancer cell lines (HCT15, HT29, DLD - 1, SW480 and COLO205), ovarian cancer cell lines (OVCAR - 3), prostate cancer cell lines (PC - 3 and LNCaP) and Non small cell lung cancer cell lines (NCI - H1781, HCC827, Calu - 1 and Calu - 3). Use MMAE in standalone drug form and SG2057 (cAS #: 260417-62-7, MedKooBiosciences) as PBD dimer included in the ADC prepared according to Example 3. Inoculate each cancer cell line from 500 cells/well to 5000 cells/well into a 96 well plate and culture for 24 hours, followed by treatment with concentrations ranging from 0.256pM to 100nM (5-fold continuous dilution) of ADC1, ADC2, and ADC3 produced according to Example 3, as well as individual drugs MMAE and SG2057. After 144 hours, the number of live cells was quantified using sulforhodamine B (SRB) dye or Cell titrer glo.
Click to Show/Hide
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| In Vitro Model | Breast adenocarcinoma | MDA-MB-468 cells | CVCL_0419 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | half-maximal cytotoxicity Concentration (CC50) |
1.065 nM
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High TROP2 expression (TROP2 +++) | ||
| Method Description |
Specifically, human pancreatic cancer cell lines (BxPC - 3, Capan - 1 and PATU - 8988s), breast cancer cell lines (JIMT - 1 and MDA - MB - 468), gastric cancer cell lines (NCI - N87, SNU - 601 and SNU - 620), colon cancer cell lines (HCT15, HT29, DLD - 1, SW480 and COLO205), ovarian cancer cell lines (OVCAR - 3), prostate cancer cell lines (PC - 3 and LNCaP) and Non small cell lung cancer cell lines (NCI - H1781, HCC827, Calu - 1 and Calu - 3). Use MMAE in standalone drug form and SG2057 (cAS #: 260417-62-7, MedKooBiosciences) as PBD dimer included in the ADC prepared according to Example 3. Inoculate each cancer cell line from 500 cells/well to 5000 cells/well into a 96 well plate and culture for 24 hours, followed by treatment with concentrations ranging from 0.256pM to 100nM (5-fold continuous dilution) of ADC1, ADC2, and ADC3 produced according to Example 3, as well as individual drugs MMAE and SG2057. After 144 hours, the number of live cells was quantified using sulforhodamine B (SRB) dye or Cell titrer glo.
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| In Vitro Model | Colon cancer | HT29 cells | CVCL_A8EZ | ||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | half-maximal cytotoxicity Concentration (CC50) |
3.605 nM
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High TROP2 expression (TROP2 +++) | ||
| Method Description |
Specifically, human pancreatic cancer cell lines (BxPC - 3, Capan - 1 and PATU - 8988s), breast cancer cell lines (JIMT - 1 and MDA - MB - 468), gastric cancer cell lines (NCI - N87, SNU - 601 and SNU - 620), colon cancer cell lines (HCT15, HT29, DLD - 1, SW480 and COLO205), ovarian cancer cell lines (OVCAR - 3), prostate cancer cell lines (PC - 3 and LNCaP) and Non small cell lung cancer cell lines (NCI - H1781, HCC827, Calu - 1 and Calu - 3). Use MMAE in standalone drug form and SG2057 (cAS #: 260417-62-7, MedKooBiosciences) as PBD dimer included in the ADC prepared according to Example 3. Inoculate each cancer cell line from 500 cells/well to 5000 cells/well into a 96 well plate and culture for 24 hours, followed by treatment with concentrations ranging from 0.256pM to 100nM (5-fold continuous dilution) of ADC1, ADC2, and ADC3 produced according to Example 3, as well as individual drugs MMAE and SG2057. After 144 hours, the number of live cells was quantified using sulforhodamine B (SRB) dye or Cell titrer glo.
Click to Show/Hide
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| In Vitro Model | Pancreatic ductal adenocarcinoma | BxPC-3 cells | CVCL_0186 | ||