Payload Information

General Information of This Payload
Payload ID
PAY0MZOZX
Name
Alpha-amanitin
Synonyms
Alpha-amanitin; 23109-05-9; alpha-Amanitine; .alpha.-Amanitin; HSDB 3458; C39H54N10O14S; EINECS 245-432-2; BRN 1071138; C39-H54-N10-O14-S; CHEMBL3792970; SCHEMBL16491633; Cyclic(L-asparaginyl-4-hydroxy-L-prolyl-(R)-4,5-dihydroxy-L-isoleucyl-6-hydroxy-2-mercapto-L-tryptophylglycyl-L-isoleucylglycyl-L-cysteinyl), cyclic (4-8)-sulfide, (R)-S-oxide; AKOS024457936; CS-5321; HY-19610; 11000-43-4; cyclo[L-Asparaginyl-4-hydroxy-L-proly-(R-4,5-dihydroxy-L-isoleucyl-6-hydroxy-2-mercapto-L-tryptophylglycyl-L-isoleucylglycyl-L-cysteinyl]cyclic (4?8)-sulfide (R)-S-oxide
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Target(s) DNA-directed RNA polymerase II subunit RPB2 (POLR2B); DNA-directed RNA polymerase III subunit RPC7 (POLR3G)
 Target Info 
Structure
Formula
C39H54N10O14S
Isosmiles
CC[C@H](C)[C@H]1C(=O)NCC(=O)N[C@H]2CS(=O)C3=C(C[C@@H](C(=O)NCC(=O)N1)NC(=O)[C@@H](NC(=O)[C@@H]4C[C@H](CN4C(=O)[C@@H](NC2=O)CC(=O)N)O)[C@@H](C)[C@H](CO)O)C5=C(N3)C=C(C=C5)O
PubChem CID
441541
InChI
InChI=1S/C39H54N10O14S/c1-4-16(2)31-36(60)42-11-29(55)43-25-15-64(63)38-21(20-6-5-18(51)7-22(20)46-38)9-23(33(57)41-12-30(56)47-31)44-37(61)32(17(3)27(53)14-50)48-35(59)26-8-19(52)13-49(26)39(62)24(10-28(40)54)45-34(25)58/h5-7,16-17,19,23-27,31-32,46,50-53H,4,8-15H2,1-3H3,(H2,40,54)(H,41,57)(H,42,60)(H,43,55)(H,44,61)(H,45,58)(H,47,56)(H,48,59)/t16-,17-,19+,23-,24-,25-,26-,27-,31-,32-,64?/m0/s1
InChIKey
CIORWBWIBBPXCG-JAXJKTSHSA-N
IUPAC Name
2-[(1R,4S,8R,10S,13S,16S,34S)-34-[(2S)-butan-2-yl]-13-[(2R,3R)-3,4-dihydroxybutan-2-yl]-8,22-dihydroxy-2,5,11,14,27,30,33,36,39-nonaoxo-27lambda4-thia-3,6,12,15,25,29,32,35,38-nonazapentacyclo[14.12.11.06,10.018,26.019,24]nonatriaconta-18(26),19(24),20,22-tetraen-4-yl]acetamide
Pharmaceutical Properties
Molecule Weight
919
Polar area
400
Complexity
1840
xlogp Value
-4.4
Heavy Count
64
Rot Bonds
7
Hbond acc
15
Hbond Donor
13
The activity data of This Payload
Standard Type Value Units Cell line Disease Model Cell line ID Reference
Half Maximal Inhibitory Concentration (IC50) 1 nM
HeLa cells
Endocervical adenocarcinoma
CVCL_0030 
[1]
Half Maximal Inhibitory Concentration (IC50) 1000 nM
HeLa cells
Endocervical adenocarcinoma
CVCL_0030 
[1]
Half Maximal Inhibitory Concentration (IC50) 1000 nM
HEK293 cells
Normal
CVCL_0045 
[1]
Half Maximal Inhibitory Concentration (IC50) 1000 nM
CHO cells
Normal
CVCL_0213 
[1]
Half Maximal Inhibitory Concentration (IC50) 50 nM
HT-29 cells
Colon adenocarcinoma
CVCL_0320 
[2]
Half Maximal Inhibitory Concentration (IC50) 560 nM
Hep-G2 cells
Hepatoblastoma
CVCL_0027 
[1]
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
Trastuzumab-alpha-amanitin conjugate 11 [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 28.53% (Day 87) High HER2 expression (HER2 +++)
Method Description
A mouse tumor xenograft model, wherein 250,000,000 SKOV-3 ovarial carcinoma cellsare implated sub-cutaneously (s.c,) into SCID mice and allowed to grow for 10 days. After 10 days a single dose of 30 ug/kg body weight of various a-amanitin-Herceptin conjugates.
In Vivo Model SK-OV-3 CDX model
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 94.60% (Day 87) High HER2 expression (HER2 +++)
Method Description
A mouse tumor xenograft model, wherein 250,000,000 SKOV-3 ovarial carcinoma cellsare implated sub-cutaneously (s.c,) into SCID mice and allowed to grow for 10 days. After 10 days a single dose of 150 ug/kg body weight of various a-amanitin-Herceptin conjugates.
In Vivo Model SK-OV-3 CDX model
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Trastuzumab-alpha-amanitin conjugate 4 [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 37.30% (Day 87) High HER2 expression (HER2 +++)
Method Description
A mouse tumor xenograft model, wherein 250,000,000 SKOV-3 ovarial carcinoma cellsare implated sub-cutaneously (s.c,) into SCID mice and allowed to grow for 10 days. After 10 days a single dose of 30 ug/kg body weight of various a-amanitin-Herceptin conjugates.
In Vivo Model SK-OV-3 CDX model
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 76.05% (Day 87) High HER2 expression (HER2 +++)
Method Description
A mouse tumor xenograft model, wherein 250,000,000 SKOV-3 ovarial carcinoma cellsare implated sub-cutaneously (s.c,) into SCID mice and allowed to grow for 10 days. After 10 days a single dose of 150 ug/kg body weight of various a-amanitin-Herceptin conjugates.
In Vivo Model SK-OV-3 CDX model
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Trastuzumab-alpha-amanitin conjugate 10 [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 55.08% (Day 87) High HER2 expression (HER2 +++)
Method Description
A mouse tumor xenograft model, wherein 250,000,000 SKOV-3 ovarial carcinoma cellsare implated sub-cutaneously (s.c,) into SCID mice and allowed to grow for 10 days. After 10 days a single dose of 30 ug/kg body weight of various a-amanitin-Herceptin conjugates.
In Vivo Model SK-OV-3 CDX model
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.16% (Day 87) High HER2 expression (HER2 +++)
Method Description
A mouse tumor xenograft model, wherein 250,000,000 SKOV-3 ovarial carcinoma cellsare implated sub-cutaneously (s.c,) into SCID mice and allowed to grow for 10 days. After 10 days a single dose of 150 ug/kg body weight of various a-amanitin-Herceptin conjugates.
In Vivo Model SK-OV-3 CDX model
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Trastuzumab-alpha-amanitin conjugate 3 [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 71.25% (Day 87) High HER2 expression (HER2 +++)
Method Description
A mouse tumor xenograft model, wherein 250,000,000 SKOV-3 ovarial carcinoma cellsare implated sub-cutaneously (s.c,) into SCID mice and allowed to grow for 10 days. After 10 days a single dose of 30 ug/kg body weight of various a-amanitin-Herceptin conjugates.
In Vivo Model SK-OV-3 CDX model
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 85.43% (Day 87) High HER2 expression (HER2 +++)
Method Description
A mouse tumor xenograft model, wherein 250,000,000 SKOV-3 ovarial carcinoma cellsare implated sub-cutaneously (s.c,) into SCID mice and allowed to grow for 10 days. After 10 days a single dose of 150 ug/kg body weight of various a-amanitin-Herceptin conjugates.
In Vivo Model SK-OV-3 CDX model
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
OHPAS ADC-1 [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 74.10% (Day 78) High HER2 expression (HER2 +++)
Method Description
We also tested the OHPAS ADCs in in vivo xenograft mouse models using N87 cell lines. The experiment was followed up to 110 days after administration of ADCs at two different doses (0.5 mg/kg) on day one (initial tumor volume 100 mm3).
In Vivo Model NCI-N87 CDX model
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.50% (Day 78) High HER2 expression (HER2 +++)
Method Description
We also tested the OHPAS ADCs in in vivo xenograft mouse models using N87 cell lines. The experiment was followed up to 110 days after administration of ADCs at two different doses (2 mg/kg) on day one (initial tumor volume 100 mm3).
In Vivo Model NCI-N87 CDX model
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
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 [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.03 nM
High HER2 expression (HER2 +++)
Method Description
With OHPAS ADCs 1-4 , we first performed cell-based MTT assays against a series of HER2 positive/negative cell lines using the commercially available HER2 ADC, T-DM1 (average DAR 3.5), which we purchased as a positive control.
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.12 nM
High HER2 expression (HER2 +++)
Method Description
With OHPAS ADCs 1-4 , we first performed cell-based MTT assays against a series of HER2 positive/negative cell lines using the commercially available HER2 ADC, T-DM1 (average DAR 3.5), which we purchased as a positive control.
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Experiment 3 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.60 nM
High HER2 expression (HER2 +++)
Method Description
With OHPAS ADCs 1-4 , we first performed cell-based MTT assays against a series of HER2 positive/negative cell lines using the commercially available HER2 ADC, T-DM1 (average DAR 3.5), which we purchased as a positive control.
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 4 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 50.00 nM Moderate HER2 expression (HER2 ++)
Method Description
With OHPAS ADCs 1-4 , we first performed cell-based MTT assays against a series of HER2 positive/negative cell lines using the commercially available HER2 ADC, T-DM1 (average DAR 3.5), which we purchased as a positive control.
In Vitro Model Breast ductal carcinoma JIMT-1 cells CVCL_2077
Experiment 5 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 50.00 nM Negative HER2 expression (HER2 -)
Method Description
With OHPAS ADCs 1-4 , we first performed cell-based MTT assays against a series of HER2 positive/negative cell lines using the commercially available HER2 ADC, T-DM1 (average DAR 3.5), which we purchased as a positive control.
In Vitro Model Invasive breast carcinoma MCF-7 cells CVCL_0031
Trastuzumab-alpha-amanitin conjugate 15 [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 86.62% (Day 87) High HER2 expression (HER2 +++)
Method Description
A mouse tumor xenograft model, wherein 250,000,000 SKOV-3 ovarial carcinoma cellsare implated sub-cutaneously (s.c,) into SCID mice and allowed to grow for 10 days. After 10 days a single dose of 30 ug/kg body weight of various a-amanitin-Herceptin conjugates.
In Vivo Model SK-OV-3 CDX model
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.16% (Day 87) High HER2 expression (HER2 +++)
Method Description
A mouse tumor xenograft model, wherein 250,000,000 SKOV-3 ovarial carcinoma cellsare implated sub-cutaneously (s.c,) into SCID mice and allowed to grow for 10 days. After 10 days a single dose of 150 ug/kg body weight of various a-amanitin-Herceptin conjugates.
In Vivo Model SK-OV-3 CDX model
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Trastuzumab-alpha-amanitin conjugate 7 [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 90.64% (Day 87) High HER2 expression (HER2 +++)
Method Description
A mouse tumor xenograft model, wherein 250,000,000 SKOV-3 ovarial carcinoma cellsare implated sub-cutaneously (s.c,) into SCID mice and allowed to grow for 10 days. After 10 days a single dose of 30 ug/kg body weight of various a-amanitin-Herceptin conjugates.
In Vivo Model SK-OV-3 CDX model
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.16% (Day 87) High HER2 expression (HER2 +++)
Method Description
A mouse tumor xenograft model, wherein 250,000,000 SKOV-3 ovarial carcinoma cellsare implated sub-cutaneously (s.c,) into SCID mice and allowed to grow for 10 days. After 10 days a single dose of 150 ug/kg body weight of various a-amanitin-Herceptin conjugates.
In Vivo Model SK-OV-3 CDX model
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
WO2017089895A1 ADC21 [Investigative]
 ADC Info 
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 [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.09 nM
Positive HER2 expression (HER2+++/++)
Method Description
Anti-proliferation activities of the antibodies, drugs, and conjugates with regard tothe cancer cell lines were measured. The cells were plated in 96-well, tissue culture platesat 10,000 cells per well. After 24 hour incubation, the antibodies, drugs, and conjugateswere added in various concentrations. The number of viable cells after 72 hours were counted using SRB assay.

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In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.25 nM
Positive HER2 expression (HER2+++/++)
Method Description
Anti-proliferation activities of the antibodies, drugs, and conjugates with regard tothe cancer cell lines were measured. The cells were plated in 96-well, tissue culture platesat 10,000 cells per well. After 24 hour incubation, the antibodies, drugs, and conjugateswere added in various concentrations. The number of viable cells after 72 hours were counted using SRB assay.

   Click to Show/Hide
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Experiment 3 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.88 nM
Positive HER2 expression (HER2+++/++)
Method Description
Anti-proliferation activities of the antibodies, drugs, and conjugates with regard tothe cancer cell lines were measured. The cells were plated in 96-well, tissue culture platesat 10,000 cells per well. After 24 hour incubation, the antibodies, drugs, and conjugateswere added in various concentrations. The number of viable cells after 72 hours were counted using SRB assay.

   Click to Show/Hide
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 4 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 33.30 nM Positive HER2 expression (HER2+++/++)
Method Description
Anti-proliferation activities of the antibodies, drugs, and conjugates with regard tothe cancer cell lines were measured. The cells were plated in 96-well, tissue culture platesat 10,000 cells per well. After 24 hour incubation, the antibodies, drugs, and conjugateswere added in various concentrations. The number of viable cells after 72 hours were counted using SRB assay.

   Click to Show/Hide
In Vitro Model Breast ductal carcinoma JIMT-1 cells CVCL_2077
Experiment 5 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 33.30 nM Negative HER2 expression (HER2-)
Method Description
Anti-proliferation activities of the antibodies, drugs, and conjugates with regard tothe cancer cell lines were measured. The cells were plated in 96-well, tissue culture platesat 10,000 cells per well. After 24 hour incubation, the antibodies, drugs, and conjugateswere added in various concentrations. The number of viable cells after 72 hours were counted using SRB assay.

   Click to Show/Hide
In Vitro Model Invasive breast carcinoma MCF-7 cells CVCL_0031
WO2017089890A1 ADC21 [Investigative]
 ADC Info 
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 [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.09 nM
High HER2 expression (HER2 +++)
Method Description
Anti-proliferation activities of the antibodies, drugs, and conjugates with regard tothe cancer cell lines were measured. The cells were plated in 96-well, tissue culture platesat 10,000 cells per well. After 24 hour incubation, the antibodies, drugs, and conjugateswere added in various concentrations. The number of viable cells after 72 hours werecounted using SRB assay.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.25 nM
High HER2 expression (HER2+++)
Method Description
Anti-proliferation activities of the antibodies, drugs, and conjugates with regard tothe cancer cell lines were measured. The cells were plated in 96-well, tissue culture platesat 10,000 cells per well. After 24 hour incubation, the antibodies, drugs, and conjugateswere added in various concentrations. The number of viable cells after 72 hours werecounted using SRB assay.

   Click to Show/Hide
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Experiment 3 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.88 nM
High HER2 expression (HER2+++)
Method Description
Anti-proliferation activities of the antibodies, drugs, and conjugates with regard tothe cancer cell lines were measured. The cells were plated in 96-well, tissue culture platesat 10,000 cells per well. After 24 hour incubation, the antibodies, drugs, and conjugateswere added in various concentrations. The number of viable cells after 72 hours werecounted using SRB assay.

   Click to Show/Hide
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 4 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 33.30 nM Moderate HER2 expression (HER2++)
Method Description
Anti-proliferation activities of the antibodies, drugs, and conjugates with regard tothe cancer cell lines were measured. The cells were plated in 96-well, tissue culture platesat 10,000 cells per well. After 24 hour incubation, the antibodies, drugs, and conjugateswere added in various concentrations. The number of viable cells after 72 hours werecounted using SRB assay.

   Click to Show/Hide
In Vitro Model Breast ductal carcinoma JIMT-1 cells CVCL_2077
Experiment 5 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 33.30 nM Negative HER2 expression (HER2-)
Method Description
Anti-proliferation activities of the antibodies, drugs, and conjugates with regard tothe cancer cell lines were measured. The cells were plated in 96-well, tissue culture platesat 10,000 cells per well. After 24 hour incubation, the antibodies, drugs, and conjugateswere added in various concentrations. The number of viable cells after 72 hours werecounted using SRB assay.

   Click to Show/Hide
In Vitro Model Invasive breast carcinoma MCF-7 cells CVCL_0031
References
Ref 1 Rationally Designed Amanitins Achieve Enhanced Cytotoxicity. J Med Chem. 2022 Aug 11;65(15):10357-10376. doi: 10.1021/acs.jmedchem.1c02226. Epub 2022 Jun 13.
Ref 2 3-substituted 7-phenyl-pyrroloquinolinones show potent cytotoxic activity in human cancer cell lines. J Med Chem. 2007 Nov 1;50(22):5509-13. doi: 10.1021/jm070534b. Epub 2007 Oct 4.
Ref 3 Amatoxin-armed therapeutic cell surface binding components designed for tumour therapy.
Ref 4 Aryl Sulfate is a Useful Motif for Conjugating and Releasing Phenolic Molecules: Sulfur Fluorine Exchange Click Chemistry Enables Discovery of Ortho-Hydroxy-Protected Aryl Sulfate Linker. Bioconjug Chem. 2019 Jul 17;30(7):1957-1968. doi: 10.1021/acs.bioconjchem.9b00340. Epub 2019 Jun 28.
Ref 5 Antibody-drug conjugates comprising branched linkers and methods related thereto; 2017-06-01.
Ref 6 Conjugates comprising self-immolative groups and methods related thereto.

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