The antibody-drug conjugate (ADC), a humanized or human monoclonal antibody conjugated with highly cytotoxic small molecules (payloads) through chemical linkers, is a novel therapeutic format and has great potential to make a paradigm shift in cancer chemotherapy. The three components of the ADC together give rise to a powerful oncolytic agent capable of delivering normally intolerable cytotoxins directly to cancer cells, which then internalize and release the cell-destroying drugs. At present, two ADCs, Adcetris and Kadcyla, have received regulatory approval with >40 others in clinical development.

ADCs are administered intravenously in order to prevent the mAb from being destroyed by gastric acids and proteolytic enzymes. The mAb component of the ADC enables it to circulate in the bloodstream until it finds and binds to tumor-specific cell surface antigens present on target cancer cells. Linker chemistry is an important determinant of the safety, specificity, potency and activity of ADCs. Linkers are designed to be stable in the blood stream (to conform to the increased circulation time of mAbs) and labile at the cancer site to allow rapid release of the cytotoxic drug. First generation ADCs made use of early cytotoxins such as the anthracycline, doxorubicin or the anti-metabolite/antifolate agent, methotrexate. Current cytotoxins have far greater potency and can be divided into three main groups: auristatins, maytansines and calicheamicins.

The development of site-specific conjugation methodologies for constructing homogeneous ADCs is an especially promising path to improving ADC design, which will open the way for novel cancer therapeutics.

References:
[1] Tsuchikama K, et al. Protein Cell. 2016 Oct 14. DOI:10.1007/s13238-016-0323-0.
[2] Peters C, et al. Biosci Rep. 2015 Jun 12;35(4). pii: e00225. doi: 10.1042/BSR20150089.


Anti-infection >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
Autophagy >
Autophagy LRRK2 ULK Mitophagy
Cell Cycle/DNA Damage >
Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
Cytoskeleton >
Arp2/3 Complex Dynamin Gap Junction Protein Integrin Kinesin Microtubule/Tubulin Mps1 Myosin PAK
Epigenetics >
AMPK Aurora Kinase DNA Methyltransferase Epigenetic Reader Domain HDAC Histone Acetyltransferase Histone Demethylase Histone Methyltransferase JAK MicroRNA PARP PKC Sirtuin Protein Arginine Deiminase
GPCR/G Protein >
5-HT Receptor Adenosine Receptor Adenylate Cyclase Adiponectin Receptor Adrenergic Receptor Angiotensin Receptor Bombesin Receptor Bradykinin Receptor Cannabinoid Receptor CaSR CCR CGRP Receptor Cholecystokinin Receptor CRFR CXCR Dopamine Receptor EBI2/GPR183 Endothelin Receptor GHSR Glucagon Receptor Glucocorticoid Receptor GNRH Receptor GPCR19 GPR109A GPR119 GPR120 GPR139 GPR40 GPR55 GPR84 Guanylate Cyclase Histamine Receptor Imidazoline Receptor Leukotriene Receptor LPL Receptor mAChR MCHR1 (GPR24) Melatonin Receptor mGluR Motilin Receptor Neurokinin Receptor Neuropeptide Y Receptor Neurotensin Receptor Opioid Receptor Orexin Receptor (OX Receptor) Oxytocin Receptor P2Y Receptor Prostaglandin Receptor Protease-Activated Receptor (PAR) Ras RGS Protein Sigma Receptor Somatostatin Receptor TSH Receptor Urotensin Receptor Vasopressin Receptor Melanocortin Receptor
Immunology/Inflammation >
Aryl Hydrocarbon Receptor CCR Complement System COX CXCR FLAP Histamine Receptor IFNAR Interleukin Related IRAK MyD88 NO Synthase NOD-like Receptor (NLR) PD-1/PD-L1 PGE synthase Salt-inducible Kinase (SIK) SPHK STING Thrombopoietin Receptor Toll-like Receptor (TLR) Arginase
JAK/STAT Signaling >
EGFR JAK Pim STAT
MAPK/ERK Pathway >
ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
Membrane Transporter/Ion Channel >
ATP Synthase BCRP Calcium Channel CFTR Chloride Channel CRAC Channel CRM1 EAAT2 GABA Receptor GlyT HCN Channel iGluR Monoamine Transporter Monocarboxylate Transporter Na+/Ca2+ Exchanger Na+/HCO3- Cotransporter Na+/K+ ATPase nAChR NKCC P-glycoprotein P2X Receptor Potassium Channel Proton Pump SGLT Sodium Channel TRP Channel URAT1
Metabolic Enzyme/Protease >
15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
Neuronal Signaling >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
NF-κB >
NF-κB IKK Keap1-Nrf2 MALT1
PI3K/Akt/mTOR >
Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
PROTAC >
PROTAC E3 Ligase Ligand-Linker Conjugate Ligand for E3 Ligase PROTAC Linker PROTAC-linker Conjugate for PAC
Protein Tyrosine Kinase/RTK >
Ack1 ALK Bcr-Abl BMX Kinase Btk c-Fms c-Kit c-Met/HGFR Discoidin Domain Receptor DYRK EGFR Ephrin Receptor FAK FGFR FLT3 IGF-1R Insulin Receptor IRAK Itk PDGFR PKA Pyk2 ROS Src Syk TAM Receptor Trk Receptor VEGFR
Stem Cell/Wnt >
Casein Kinase ERK Gli GSK-3 Hedgehog Hippo (MST) JAK Notch Oct3/4 PKA Porcupine ROCK sFRP-1 Smo STAT TGF-beta/Smad Wnt YAP β-catenin γ-secretase
TGF-beta/Smad >
TGF-beta/Smad PKC ROCK TGF-β Receptor
Vitamin D Related >
VD/VDR
Others >
Androgen Receptor Aromatase Estrogen Receptor/ERR Progesterone Receptor Thyroid Hormone Receptor Others

Ald-Ph-amido-PEG3-NHS ester

Ald-Ph-amido-PEG3-NHS ester is a non-cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2101206-32-8
  • MF: C21H26N2O9
  • MW: 450.44
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amino-PEG4-CH2COOH

Amino-PEG4-CH2COOH is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1]. Amino-PEG4-CH2COOH is also a non-cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[2].

  • CAS Number: 195071-49-9
  • MF: C10H21NO6
  • MW: 251.27700
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MC-DOXHZN hydrochloride

MC-DOXHZN hydrochloride is an albumin-binding prodrug of Doxorubicin, with acid-sensitive properties[1].

  • CAS Number: 480998-12-7
  • MF: C37H43ClN4O13
  • MW: 787.21
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cyclooctyne-O-amido-PEG3-PFP ester

Cyclooctyne-O-amido-PEG3-PFP ester is a non-cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2101206-33-9
  • MF: C25H30F5NO7
  • MW: 551.50
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MC-Val-Cit-PAB-duocarmycin

MC-Val-Cit-PAB-duocarmycin has a bioreversible linkage based on a quaternary ammonium for targeted delivery and it can improve pharmacokinetics and the therapeutic index. MC-Val-Cit-PAB-duocarmycin is used for the antibody-drug conjugates (ADC) that are effective and stable in vitro and in vivo to treat various diseases or disorders[1].

  • CAS Number: 2055896-98-3
  • MF: C54H65ClN9O9
  • MW: 1019.60
  • Catalog: Drug-Linker Conjugates for ADC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methotrexate-d3

Methotrexate-d3 (Amethopterin-d3) is the deuterium labeled Methotrexate. Methotrexate (Amethopterin), an antimetabolite and antifolate agent, inhibits the enzyme dihydrofolate reductase, thereby preventing the conversion of folic acid into tetrahydrofolate, and inhibiting DNA synthesis. Methotrexate, also an immunosuppressant and antineoplastic agent, is used for the research of rheumatoid arthritis and a number of different cancers (such as acute lymphoblastic leukemia)[1][2][3].

  • CAS Number: 432545-63-6
  • MF: C20H19D3N8O5
  • MW: 457.45800
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 210°C dec.
  • Flash Point: 9℃

Thailanstatin A

Thailanstatin A is an ultra-potent inhibitor of eukaryotic RNA splicing (IC50=650 nM). Thailanstatin A exerts effects via non-covalent binding to the SF3b subunit of the U2 snRNA subcomplex of the spliceosome and shows low-nM to sub-nM IC50s against multiple cancer cell lines. Thailanstatin A, a payload for ADCs, is conjugated to the lysines on trastuzumab yielding “linker-less” ADC[1][2][3].

  • CAS Number: 1426953-21-0
  • MF: C28H41NO9
  • MW: 535.63
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG11-acid

m-PEG11-acid is a non-cleavable 11 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1]. m-PEG11-acid is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[2].

  • CAS Number: 2280998-74-3
  • MF: C24H48O13
  • MW: 544.63
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Propargyl-NHS Ester

Propargyl-PEG1-NHS ester is a nonclaevable 1-unit PEG linker for antibody-drug-conjugation (ADC).

  • CAS Number: 1174157-65-3
  • MF: C10H11NO5
  • MW: 225.19800
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 36-41°C
  • Flash Point: N/A

Mal-Ph-CONH-PEG4-NHS ester

Mal-Ph-CONH-PEG4-​NHS ester is a non-cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1263044-88-7
  • MF: C26H31N3O11
  • MW: 561.54
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MC-VC-PABC

MC-VC-PABC is a noncleavable ADC linker used in the synthesis of antibody-drug conjugates[1].

  • CAS Number: 1703779-06-9
  • MF: C68H107N11O15
  • MW: 1318.64
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fmoc-Phe-Lys(Trt)-PAB

Fmoc-Phe-Lys(Trt)-PAB is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1116085-98-3
  • MF: C56H54N4O5
  • MW: 863.05
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cyclooctyne-O-amido-PEG3-NHS ester

Cyclooctyne-O-amido-PEG3-NHS ester is a non-cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2101206-34-0
  • MF: C23H34N2O9
  • MW: 482.52
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Seco-DUBA hydrochloride

Seco-DUBA hydrochloride is a toxin for ADC drug SYD985[1].

  • CAS Number: 1795733-93-5
  • MF: C29H23ClN4O4.xClH
  • MW:
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DBCO-Sulfo-NHS ester

DBCO-Sulfo-NHS ester sodium is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1400191-52-7
  • MF: C25H21N2NaO8S
  • MW: 532.50
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Boc-Hyp-OH

Boc-Hyp-OH is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Boc-Hyp-OH is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1][2]

  • CAS Number: 13726-69-7
  • MF: C10H17NO5
  • MW: 231.246
  • Catalog: ADC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 390.9±42.0 °C at 760 mmHg
  • Melting Point: 123-127 °C(lit.)
  • Flash Point: 190.2±27.9 °C

Acid-PEG2-SS-PEG2-acid

Acid-PEG2-SS-PEG2-acid is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1807539-10-1
  • MF: C14H26O8S2
  • MW: 386.481
  • Catalog: ADC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 573.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 300.9±30.1 °C

DC1

DC1, an analogue of the minor groove-binding DNA alkylator CC-1065, is an antibody conjugate of cytotoxic DNA alkylators for the targeted treatment of cancer.

  • CAS Number: 169901-27-3
  • MF: C34H28ClN5O4S
  • MW: 638.14
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

D-Proline, 4-hydroxy-, methyl ester hydrochloride

D-Proline, 4-hydroxy-, methyl ester hydrochloride is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). D-Proline, 4-hydroxy-, methyl ester hydrochloride is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1][2

  • CAS Number: 114676-59-4
  • MF: C6H12ClNO3
  • MW: 181.617
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 121-123 ºC
  • Flash Point: N/A

m-PEG12-OH

m-PEG12-OH is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1]. m-PEG12-OH is also a non-cleavable 12 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[2].

  • CAS Number: 2050595-03-2
  • MF: C25H52O13
  • MW: 560.67
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(4E)-TCO-PEG4-DBCO

TCO-PEG4-DBCO is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1801863-88-6
  • MF: C38H49N3O8
  • MW: 675.81
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azetidin-3-ol hydrochloride

Azetidin-3-ol hydrochloride is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azetidin-3-ol hydrochloride is also a alkyl chain-based PROTAC linker that can be used in the synthes PROTAC.

  • CAS Number: 18621-18-6
  • MF: C3H8ClNO
  • MW: 109.555
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: 170.7ºC at 760 mmHg
  • Melting Point: 90-92°C
  • Flash Point: 120.4ºC

MC-Val-Cit-PAB-OH

MC-Val-Cit-PAB is a cathepsin cleavable ADC linker that is used for making antibody-drug conjugate. FDA approved drugs such as brentuximab vedotin use this linker.

  • CAS Number: 159857-80-4
  • MF: C28H40N6O7
  • MW: 572.65300
  • Catalog: ADC Linker
  • Density: 1.276
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aminoxyacetamide-PEG3-azide

Aminoxyacetamide-PEG3-azide is a non-cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1379761-16-6
  • MF: C10H21N5O5
  • MW: 291.30
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CL2A

CL2A is a complicated PEG8- and triazole-containing PABC-peptide-mc linker. CL2A is cleavable through pH sensitivity, giving rise to bystander effect, and binds the antibody at a cysteine residue via a disulfide bond. Labetuzumab govitecan used this linker[1].

  • CAS Number: 1846605-04-6
  • MF: C51H79N9O18
  • MW: 1106.22
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amino-Tri-(t-butoxycarbonylethoxymethyl)-methane

Tris[[2-(tert-butoxycarbonyl)ethoxy]methyl]methylamine is a cleavable PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Amino-Tri-(t-butoxycarbonylethoxymethyl)-methane is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

  • CAS Number: 175724-30-8
  • MF: C25H47NO9
  • MW: 505.64200
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BS3 Crosslinker disodium

BS3 Crosslinker disodium is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 127634-19-9
  • MF: C16H18N2Na2O14S2
  • MW: 572.42900
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mc-Val-Cit-PABC-PNP

Mc-Val-Cit-PABC-PNP is a cathepsin cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).

  • CAS Number: 159857-81-5
  • MF: C35H43N7O11
  • MW: 737.756
  • Catalog: ADC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1034.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 579.4±34.3 °C

CL2-SN-38

CL2-SN-38 is a part of the antibody drug conjugate (ADC), can conjugate with the anti-Trop-2-humanized antibody hRS7. The anti-Trop-2 hRS7-CL2A-SN-38 ADC provides significant and specific antitumor effects against a range of human solid tumor types[1].

  • CAS Number: 1036969-20-6
  • MF: C83H107N11O23
  • MW: 1626.80
  • Catalog: Drug-Linker Conjugates for ADC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG4-Val-Cit-PAB-OH

Azido-PEG4-Val-Cit-PAB-OH is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1]. Azido-PEG4-Val-Cit-PAB-OH is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[2].

  • CAS Number: 2055024-64-9
  • MF: C29H48N8O9
  • MW: 652.74
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A