Endogenous coupling of amino acids and Disulfide re bridging strategy
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Endogenous coupling of amino acids
One of the most common coupling methods is to use the lysine residue of the antibody, the amino acid nucleophilic NH2 group, to react with the electrophilic N-hydroxysuccinimide (NHS) Group on the lik payload. Although the reaction is simple, the high abundance of available lysine residues leads to the formation of uneven mixtures of many ADCs under random distribution. DAR is controlled by antibody-drug conjugates stoichiometry, which is widely used, including approved ADCs such as Besponsa, Mylotarg, and Kadcyla.
Disulfide re bridging strategy
IgG antibodies contain four disulfide bonds between chains, two connecting light chains and heavy chains, and two are located in the hinge region connecting two heavy chains. They maintain the integrity of monoclonal antibodies. Another classic biological coupling pathway explores the role of these cysteines as payload attachment points. The reduction of four disulfide bonds usually produces eight sulfhydryl groups, which can react with the linker of maleimide to produce ADC with DAR=8.
Dorona and colleagues reported an example of an ADC with a chimeric anti-CD30 monoclonal antibody coupled to MMAE, DAR= 8. Compared with the classical lysine coupling, this payload loading method is better controlled. However, it is reported that the plasma clearance rate will be higher and the risk of plasma aggregation will be reduced.
In 2015, chudasama et al. Introduced a new type of re bridging reagent, dibromopyridazinediones. They proved that it can be effectively inserted into the disulfide bond, and the resulting structure shows excellent hydrolytic stability even at high temperature. However, with the increase of temperature on the reduction step, heterogeneity is also observed, and this structure also allows the selective introduction of different functional groups.
Divinylpyrimidine is another effective re-bridging reagent, which can produce stable ADC with Dar = 4. Spring et al. Studied the effect of vinyl heteroaryl scaffold on cysteine re bridging. They believe that replacing pyridine with pyrimidine can make heteroaryl ring a better electron acceptor, so as to improve the crosslinking efficiency. Their work extends to divinyltriazine, which shows higher efficiency at high temperature.
In order to avoid the disadvantage of in vivo instability associated with classical maleimide coupling, Barbas et al studied methylsulfonylphenyloxadiazole, which has a specific reaction to cysteine. They are more stable than cysteine maleimide conjugates in plasma. Inspired by this, Zeglis designed dipods reagent, which contains two oxadiazole methyl sulfone parts connected by phenyl. Dipods forms covalent bonds with two sulfate radicals in the way of re bridging. Compared with maleimide coupling, coupling in this way has superior stability in vitro and performance in vivo.
Product List
Cat No. | Products Name (INN Index) | INN Name | Previous Name | Target | Format | Order |
|---|---|---|---|---|---|---|
Pre-Made Telimomab Aritox Biosimilar, Whole Mab Adc, Anti-Cd5 Antibody: Anti-LEU1/T1 therapeutic antibody |
telimomab aritox |
NA |
CD5 |
ADC |
||
Pre-Made Telisotuzumab Vedotin Biosimilar, Whole Mab Adc, Anti-Met Antibody: Anti-AUTS9/DFNB97/HGFR/RCCP2/c-Met therapeutic antibody Drug Conjugate |
telisotuzumab vedotin |
NA |
MET |
Whole mAb ADC |
||
Pre-Made Tisotumab Vedotin Biosimilar, Whole Mab Adc, Anti-F3 Antibody: Anti-CD142/TF/TFA therapeutic antibody Drug Conjugate |
tisotumab vedotin |
NA |
F3 |
Whole mAb ADC |
||
Pre-Made Trastuzumab Deruxtecan Biosimilar, Whole Mab Adc, Anti-ERBB2/HER2 Antibody: Anti-CD340/neu/MLN 19/NEU/NGL/TKR1/VSCN2/c-ERB-2/c-ERB2 therapeutic antibody Drug Conjugate |
trastuzumab deruxtecan |
NA |
ERBB2 |
Whole mAb ADC |
||
Pre-Made Trastuzumab Duocarmazine Biosimilar, Whole Mab Adc, Anti-ERBB2/HER2 Antibody: Anti-CD340/neu/MLN 19/NEU/NGL/TKR1/VSCN2/c-ERB-2/c-ERB2 therapeutic antibody Drug Conjugate |
trastuzumab duocarmazine |
NA |
ERBB2 |
Whole mAb ADC |
||
Pre-Made Trastuzumab Emtansine Biosimilar, Whole Mab Adc, Anti-ERBB2/HER2 Antibody: Anti-CD340/neu/MLN 19/NEU/NGL/TKR1/VSCN2/c-ERB-2/c-ERB2 therapeutic antibody Drug Conjugate |
trastuzumab emtansine |
NA |
ERBB2 |
Whole mAb ADC |
||
Pre-Made Tusamitamab Ravtansine Biosimilar, Whole Mab Adc, Anti-CEACAM5/CD66e Antibody: Anti-CEA therapeutic antibody Drug Conjugate |
tusamitamab ravtansine |
NA |
CEACAM5 |
Whole mAb ADC |
||
Pre-Made Upifitamab Rilsodotin Biosimilar, Whole Mab Adc, Anti-Slc34A2 Antibody: Anti-NAPI-3B/NAPI-IIb/NPTIIb/PULAM therapeutic antibody Drug Conjugate |
upifitamab rilsodotin |
NA |
SLC34A2 |
Whole mAb ADC |
||
Pre-Made Vadastuximab Talirine Biosimilar, Whole Mab Adc, Anti-Cd33 Antibody: Anti-SIGLEC-3/SIGLEC3/p67 therapeutic antibody Drug Conjugate |
vadastuximab talirine |
NA |
CD33 |
Whole mAb ADC |
||
Pre-Made Vandortuzumab Vedotin Biosimilar, Whole Mab Adc, Anti-Steap1 Antibody: Anti-PRSS24/STEAP therapeutic antibody Drug Conjugate |
vandortuzumab vedotin |
NA |
STEAP1 |
Whole mAb ADC |
||
Pre-Made Vorsetuzumab Mafodotin Biosimilar, Whole Mab Adc, Anti-CD70/CD27-L Antibody: Anti-CD27LG/LPFS3/TNFSF7/TNLG8A therapeutic antibody Drug Conjugate |
vorsetuzumab mafodotin |
NA |
CD70 |
Whole mAb ADC |
||
Pre-Made Zilovertamab Vedotin Biosimilar, Whole Mab Adc, Anti-Ror1 Antibody: Anti-NTRKR1/dJ537F10.1 therapeutic antibody Drug Conjugate |
zilovertamab vedotin |
NA |
ROR1 |
Whole mAb ADC |
||
Pre-Made Zolimomab Aritox Biosimilar, Whole Mab Adc, Anti-Cd5 Antibody: Anti-LEU1/T1 therapeutic antibody |
zolimomab aritox |
NA |
CD5 |
ADC |
||
Pre-Made Actinium (225Ac) Lintuzumab Satetraxetan Biosimilar, Whole Mab Adc, Anti-Cd33 Antibody: Anti-SIGLEC-3/SIGLEC3/p67 therapeutic antibody Drug Conjugate |
actinium (225Ac) lintuzumab satetraxetan |
NA |
CD33 |
Whole mAb ADC |
||
Pre-Made Anetumab Corixetan Biosimilar, Whole Mab Adc, Anti-Msln Antibody: Anti-MPF/SMRP therapeutic antibody Drug Conjugate |
anetumab corixetan |
NA |
MSLN |
Whole mAb ADC |
||
Pre-Made Anetumab Ravtansine Biosimilar, Whole Mab Adc, Anti-Msln Antibody: Anti-MPF/SMRP therapeutic antibody Drug Conjugate |
anetumab ravtansine |
NA |
MSLN |
Whole mAb ADC |
||
Pre-Made Aprutumab Ixadotin Biosimilar, Whole Mab Adc, Anti-Fgfr2 Antibody: Anti-BBDS/BEK/BFR-1/CD332/CEK3/CFD1/ECT1/JWS/K-SAM/KGFR/TK14/TK25 therapeutic antibody Drug Conjugate |
aprutumab ixadotin |
NA |
FGFR2 |
Whole mAb ADC |
||
Pre-Made Azintuxizumab Vedotin Biosimilar, Whole Mab Adc, Anti-SLAMF7/CS1 Antibody: Anti-19A/CD319/CRACC therapeutic antibody Drug Conjugate |
azintuxizumab vedotin |
NA |
SLAMF7 |
Whole mAb ADC |
||
Pre-Made Belantamab Mafodotin Biosimilar, Whole Mab Adc, Anti-Tnfrsf17 Antibody: Anti-BCM/BCMA/CD269/TNFRSF13A therapeutic antibody Drug Conjugate |
belantamab mafodotin |
NA |
TNFRSF17 |
Whole mAb ADC |
||
Pre-Made Brentuximab Vedotin Biosimilar, Whole Mab Adc, Anti-Tnfrsf8 Antibody: Anti-CD30/D1S166E/Ki-1 therapeutic antibody Drug Conjugate |
brentuximab vedotin |
NA |
TNFRSF8 |
Whole mAb ADC |
||
Pre-Made Camidanlumab Tesirine Biosimilar, Whole Mab Adc, Anti-Il2Ra Antibody: Anti-CD25/IDDM10/IL2R/IMD41/TCGFR/p55 therapeutic antibody Drug Conjugate |
camidanlumab tesirine |
NA |
IL2RA |
Whole mAb ADC |
||
Pre-Made Cantuzumab Mertansine Biosimilar, Whole Mab Adc, Anti-Muc1 Antibody: Anti-ADMCKD/ADMCKD1/ADTKD2/CA 15-3/CD227/Ca15-3/EMA/H23AG/KL-6/MAM6/MCD/MCKD/MCKD1/SEC/X/ZD/PEM/PEMT/PUM therapeutic anti |
cantuzumab mertansine |
NA |
MUC1 |
Whole mAb ADC |
||
Pre-Made Cantuzumab Ravtansine Biosimilar, Whole Mab Adc, Anti-Muc1 Antibody: Anti-ADMCKD/ADMCKD1/ADTKD2/CA 15-3/CD227/Ca15-3/EMA/H23AG/KL-6/MAM6/MCD/MCKD/MCKD1/SEC/X/ZD/PEM/PEMT/PUM therapeutic anti |
cantuzumab ravtansine |
NA |
MUC1 |
Whole mAb ADC |
||
Pre-Made Cetuximab Sarotalocan Biosimilar, Whole Mab Adc, Anti-Egfr Antibody: Anti-ERBB/ERBB1/ERRP/HER1/NISBD2/PIG61/mENA therapeutic antibody Drug Conjugate |
cetuximab sarotalocan |
NA |
EGFR |
Whole mAb ADC |
||
Pre-Made Clivatuzumab Tetraxetan Biosimilar, Whole Mab Adc, Anti-Muc1 Antibody: Anti-ADMCKD/ADMCKD1/ADTKD2/CA 15-3/CD227/Ca15-3/EMA/H23AG/KL-6/MAM6/MCD/MCKD/MCKD1/SEC/X/ZD/PEM/PEMT/PUM therapeutic an |
clivatuzumab tetraxetan |
NA |
MUC1 |
Whole mAb ADC |
||
Pre-Made Cofetuzumab Pelidotin Biosimilar, Whole Mab Adc, Anti-Ptk7 Antibody: Anti-CCK-4/CCK4 therapeutic antibody Drug Conjugate |
cofetuzumab pelidotin |
NA |
PTK7 |
Whole mAb ADC |
||
Pre-Made Coltuximab Ravtansine Biosimilar, Whole Mab Adc, Anti-Cd19 Antibody: Anti-B4/CVID3 therapeutic antibody Drug Conjugate |
coltuximab ravtansine |
NA |
CD19 |
Whole mAb ADC |
||
Pre-Made Dafsolimab Setaritox Biosimilar, Whole Mab Adc, Anti-Cd3E Antibody: Anti-CD3epsilon/IMD18/T3E/TCRE therapeutic antibody Drug Conjugate |
dafsolimab setaritox |
NA |
CD3E |
Whole mAb ADC |
||
Pre-Made Datopotamab Deruxtecan Biosimilar, Whole Mab Adc, Anti-Tacstd2 Antibody: Anti-EGP-1/EGP1/GA733-1/GA7331/GP50/M1S1/TROP2 therapeutic antibody Drug Conjugate |
datopotamab deruxtecan |
NA |
TACSTD2 |
Whole mAb ADC |
||
Pre-Made Denintuzumab Mafodotin Biosimilar, Whole Mab Adc, Anti-Cd19 Antibody: Anti-B4/CVID3 therapeutic antibody Drug Conjugate |
denintuzumab mafodotin |
NA |
CD19 |
Whole mAb ADC |
||
Pre-Made Depatuxizumab Mafodotin Biosimilar, Whole Mab Adc, Anti-Egfr Antibody: Anti-ERBB/ERBB1/ERRP/HER1/NISBD2/PIG61/mENA therapeutic antibody Drug Conjugate |
depatuxizumab mafodotin |
NA |
EGFR |
Whole mAb ADC |
||
Pre-Made Disitamab Vedotin Biosimilar, Whole Mab Adc, Anti-ERBB2/HER2 Antibody: Anti-CD340/neu/MLN 19/NEU/NGL/TKR1/VSCN2/c-ERB-2/c-ERB2 therapeutic antibody Drug Conjugate |
disitamab vedotin |
NA |
ERBB2 |
Whole mAb ADC |
||
Pre-Made Dorlimomab Aritox Biosimilar, Whole Mab Adc: Anti-40S Ribosomal Protein S18 therapeutic antibody |
dorlimomab aritox |
NA |
40S ribosomal protein S18 |
ADC |
||
Pre-Made Enapotamab Vedotin Biosimilar, Whole Mab Adc, Anti-Axl Antibody: Anti-ARK/JTK11/Tyro7/UFO therapeutic antibody Drug Conjugate |
enapotamab vedotin |
NA |
AXL |
Whole mAb ADC |
||
Pre-Made Enfortumab Vedotin Biosimilar, Whole Mab Adc, Anti-PVRL4/NECTIN4 Antibody: Anti-EDSS1/LNIR/PRR4/nectin-4 therapeutic antibody Drug Conjugate |
enfortumab vedotin |
NA |
PVRL4 |
Whole mAb ADC |
||
Pre-Made Farletuzumab Ecteribulin Biosimilar, Whole Mab Adc, Anti-Folr1 Antibody: Anti-FBP/FOLR/FRalpha/NCFTD therapeutic antibody Drug Conjugate |
farletuzumab ecteribulin |
NA |
FOLR1 |
Whole mAb ADC |
||
Pre-Made Gemtuzumab Ozogamicin Biosimilar, Whole Mab Adc, Anti-Cd33 Antibody: Anti-SIGLEC-3/SIGLEC3/p67 therapeutic antibody Drug Conjugate |
gemtuzumab ozogamicin |
NA |
CD33 |
Whole mAb ADC |
||
Pre-Made Glembatumumab Vedotin Biosimilar, Whole Mab Adc, Anti-Gpnmb Antibody: Anti-HGFIN/NMB/PLCA3 therapeutic antibody Drug Conjugate |
glembatumumab vedotin |
NA |
GPNMB |
Whole mAb ADC |
||
Pre-Made Grisnilimab Setaritox Biosimilar, Whole Mab Adc, Anti-Cd7 Antibody: Anti-GP40/LEU-9/TP41/Tp40 therapeutic antibody Drug Conjugate |
grisnilimab setaritox |
NA |
CD7 |
Whole mAb ADC |
||
Pre-Made Iladatuzumab Vedotin Biosimilar, Whole Mab Adc, Anti-Cd79B Antibody: Anti-AGM6/B29/IGB therapeutic antibody Drug Conjugate |
iladatuzumab vedotin |
NA |
CD79B |
Whole mAb ADC |
||
Pre-Made Indatuximab Ravtansine Biosimilar, Whole Mab Adc, Anti-Sdc1 Antibody: Anti-CD138/SDC/SYND1/syndecan therapeutic antibody Drug Conjugate |
indatuximab ravtansine |
NA |
SDC1 |
Whole mAb ADC |
||
Pre-Made Indusatumab Vedotin Biosimilar, Whole Mab Adc, Anti-Gucy2C Antibody: Anti-DIAR6/GC-C/GUC2C/MECILIL/STAR therapeutic antibody Drug Conjugate |
indusatumab vedotin |
NA |
GUCY2C |
Whole mAb ADC |
||
Pre-Made Inotuzumab Ozogamicin Biosimilar, Whole Mab Adc, Anti-Cd22 Antibody: Anti-SIGLEC-2/SIGLEC2 therapeutic antibody Drug Conjugate |
inotuzumab ozogamicin |
NA |
CD22 |
Whole mAb ADC |
||
Pre-Made Labetuzumab Govitecan Biosimilar, Whole Mab Adc, Anti-CEACAM5/CD66e Antibody: Anti-CEA therapeutic antibody Drug Conjugate |
labetuzumab govitecan |
NA |
CEACAM5 |
Whole mAb ADC |
||
Pre-Made Ladiratuzumab Vedotin Biosimilar, Whole Mab Adc, Anti-Slc39A6 Antibody: Anti-LIV-1/LIV1/ZIP6 therapeutic antibody Drug Conjugate |
ladiratuzumab vedotin |
NA |
SLC39A6 |
Whole mAb ADC |
||
Pre-Made Laprituximab Emtansine Biosimilar, Whole Mab Adc, Anti-Egfr Antibody: Anti-ERBB/ERBB1/ERRP/HER1/NISBD2/PIG61/mENA therapeutic antibody Drug Conjugate |
laprituximab emtansine |
NA |
EGFR |
Whole mAb ADC |
||
Pre-Made Lifastuzumab Vedotin Biosimilar, Whole Mab Adc, Anti-Slc34A2 Antibody: Anti-NAPI-3B/NAPI-IIb/NPTIIb/PULAM therapeutic antibody Drug Conjugate |
lifastuzumab vedotin |
NA |
SLC34A2 |
Whole mAb ADC |
||
Pre-Made Loncastuximab Tesirine Biosimilar, Whole Mab Adc, Anti-Cd19 Antibody: Anti-B4/CVID3 therapeutic antibody Drug Conjugate |
loncastuximab tesirine |
NA |
CD19 |
Whole mAb ADC |
||
Pre-Made Lonigutamab Ugodotin Biosimilar, Whole Mab Adc, Anti-Igf1R Antibody: Anti-CD221/IGFIR/IGFR/JTK13 therapeutic antibody Drug Conjugate |
lonigutamab ugodotin |
NA |
IGF1R |
Whole mAb ADC |
||
Pre-Made Lorvotuzumab Mertansine Biosimilar, Whole Mab Adc, Anti-Ncam1 Antibody: Anti-CD56/MSK39/NCAM therapeutic antibody Drug Conjugate |
lorvotuzumab mertansine |
NA |
NCAM1 |
Whole mAb ADC |
View the Knowledge base of Antibody-drug Conjugate (ADC):
– What is antibody-drug conjugate (ADC)?
– Antibody-drug conjugate (ADC) in clinical application (Approved/BLA, phaseI/II/III)
– Main elements of antibody-drug conjugate (ADC)： Antibodies and their targets
– Main elements of antibody-drug conjugate (ADC)：Linker (cleavable/non-cleavable, structure and mechanism)
– Main elements of antibody-drug conjugate (ADC)：Toxins/Payloads (Classification and function)
– Toxins/Payloads (Classification and function) of Microtubule destroying drug
– Toxins/Payloads (Classification and function) of DNA damage drugs
– Toxins/Payloads (Classification and function) of Innovative drugs
– Biological coupling technology Chemical based specific in situ antibody modification
– Endogenous coupling of amino acids and Disulfide re bridging strategy
– Glycan coupling
– Site specific biological coupling of engineered antibodies and Enzymatic method
– Biological coupling with engineered unnatural amino acids
– Review for ADC production, quality control and functional assay
– Product data of ADC
