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

SCO-PEG3-NH2

SCO-PEG3-NH2 is a cleavable ADC Linker containing 3 PEG units. SCO-PEG3-NH2 can be used as a copper-free click chemical reagent for catalyst-free click reactions.

  • CAS Number: 2141976-29-4
  • MF: C17H30N2O5
  • MW: 342.43
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NAMPT inhibitor-linker 2

NAMPT inhibitor-linker 2 is a drug-linker conjugates for ADC, composed of an NAMPT inhibitor as a payload, and a linker. ADC-4 consists of an NAMPT inhibitor-linker 2 and an anti-c-Kit monoclonal antibody, exihibits potent activity against c-Kit expressing cell lines such as GIST-T1 and NCI-H526, with IC50s of <7 pM and 40 pM, respectively.

  • CAS Number: 2241014-82-2
  • MF: C34H33FN6O5
  • MW: 624.66
  • Catalog: Drug-Linker Conjugates for ADC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-PEG2-Val-Cit-PABA

Mal-PEG2-Val-Cit-PABA is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1662687-83-3
  • MF: C27H38N6O9
  • MW: 590.63
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amino-Tri-(carboxyethoxymethyl)-methane hydrochloride

Amino-Tri-(carboxyethoxymethyl)-methane hydrochloride is a cleavable PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Amino-Tri-(carboxyethoxymethyl)-methan hydrochloride is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1][2].

  • CAS Number: 1416771-72-6
  • MF: C13H24ClNO9
  • MW: 373.78
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MC-Ala-Ala-PAB

MC-Ala-Ala-PAB is a cleavable ADC Linker (ADC Linker). Fmoc-Ala-Ala-PAB can be used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1949793-44-5
  • MF: C23H30N4O6
  • MW: 458.51
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-PEG1-Val-Cit-PABC-OH

Mal-PEG1-Val-Cit-PABC-OH is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2055041-37-5
  • MF: C27H38N6O8
  • MW: 574.63
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MC-VC-PABC-Aur0101

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

  • CAS Number: 1438849-92-3
  • MF: C68H100N12O14S
  • MW: 1341.66
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DBCO-PEG4-amine

DBCO-PEG4-amine is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-PEG4-amine can be used in the synthesis of FPM-PEG4-DBCO (a homobifunctional azide-to-azide cross-linker)[1].

  • CAS Number: 1840886-10-3
  • MF: C29H37N3O6
  • MW: 523.62
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hemiasterlin derivative-1

Hemiasterlin derivative-1 is a hemiasterlin derivative. Hemiasterlin derivative-1 can be used for the synthesis of the Antibody-drug conjugate (ADC)[1].

  • CAS Number: 1887046-60-7
  • MF: C20H36N2O5
  • MW: 384.51
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-PEG2-CH2COOH

Mal-PEG2-CH2COOH is an ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 173323-23-4
  • MF: C10H13NO6
  • MW: 243.21332
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AcBut

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

  • CAS Number: 400046-53-9
  • MF: C73H97IN6O25S3
  • MW: 1681.68
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-PEG2-Val-Cit-amido-PAB-OH

Mal-PEG2-Val-Cit-amido-PAB-OH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).

  • CAS Number: 2055041-38-6
  • MF: C29H42N6O9
  • MW: 618.68
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-16-Amino-10-benzyl-6,9,12,15-tetraoxo-3-oxa-5,8,11,14-tetraazahexadecanoic acid

Gly-Gly-Phe-Gly-NH-CH2-O-CH2COOH is an ADC Linker that can be used to synthesize Drug-Linker Conjugates for ADC. Especially for the synthesis of Deruxtecan (HY-13631E), a toxic drug-linker conjugate[1].

  • CAS Number: 1599440-20-6
  • MF: C18H25N5O7
  • MW: 423.42
  • Catalog: ADC Linker
  • Density: 1.339±0.06 g/cm3(Predicted)
  • Boiling Point: 971.9±65.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

N-Boc-N-methyl-D-Valinol

N-Boc-N-methyl-D-Valinol is an ADC linker with BOC protecting group.

  • CAS Number: 2165479-27-4
  • MF: C11H23NO3
  • MW: 217.30522
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NHS-SS-biotin

NHS-SS-biotin is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 122266-55-1
  • MF: C19H28N4O6S3
  • MW: 606.69
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sulfo DBCO-Maleimide

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

  • CAS Number: 2028281-86-7
  • MF: C28H26N4O8S
  • MW: 578.59
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-PEG8-acid

Bis-PEG8-acid is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Bis-PEG8-acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1246189-43-4
  • MF: C20H38O12
  • MW: 470.51
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-PEG4-Val-Cit-PAB-OH

Mal-PEG4-Val-Cit-PAB-OH is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2055041-39-7
  • MF: C33H50N6O11
  • MW: 706.78
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fmoc-8-amino-3,6-dioxaoctanoic acid

Fmoc-8-amino-3,6-dioxaoctanoic acid (Fmoc-NH-PEG2-CH2COOH) is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 166108-71-0
  • MF: C21H23NO6
  • MW: 385.410
  • Catalog: ADC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 631.4±45.0 °C at 760 mmHg
  • Melting Point: 90-92℃
  • Flash Point: 335.6±28.7 °C

Propargyl-PEG5-amine

Propargyl-PEG5-amine is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG5-amine is a PEG-based PROTAC linker can be used in the synthesis of PROTACs[1].

  • CAS Number: 1589522-46-2
  • MF: C13H25NO5
  • MW: 275.341
  • Catalog: ADC Linker
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 360.4±37.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 166.5±20.2 °C

Ald-Ph-amido-PEG11-C2-NH2

Ald-Ph-amido-PEG11-C2-NH2 is a non-cleavable 11 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1337889-01-6
  • MF: C32H56N2O13
  • MW: 676.79
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-PEG1-NHS ester

Mal-PEG1-NHS ester is a cleavable and PEG-based ADC linker used in the synthesis of antibody-drug conjugates (ADCs).

  • CAS Number: 1807518-72-4
  • MF: C13H14N2O7
  • MW: 310.259
  • Catalog: ADC Linker
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 488.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 249.2±31.5 °C

Me-Tet-PEG4-NHBoc

Me-Tet-PEG4-NHBoc is an ADC Linker containing 4 PEG units. Me-Tet-PEG4-NHBoc can utilize its own Tetrazine group to undergo a specific inverse electron demand Diels-Alder reaction (iEDDA) with compounds with TCO groups.

  • CAS Number: 2143955-71-7
  • MF: C26H40N6O7
  • MW: 548.63
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MP-Ala-Ala-PAB

MP-Ala-Ala-PAB is a cleavable ADC Linker (ADC Linker). Fmoc-Ala-Ala-PAB can be used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1949793-47-8
  • MF: C20H24N4O6
  • MW: 416.43
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-amido-PEG8-acid

Mal-amido-PEG8-acid (example 143) is an ADC linker, extracted from patent US2018339985[1].

  • CAS Number: 1334177-86-4
  • MF: C26H44N2O13
  • MW: 592.63300
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MethylCBI-azaindole-benzamide-MOM-Boc-ethylenediamine-D

MethylCBI-azaindole-benzamide-MOM-Boc-ethylenediamine-D is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2222445-87-4
  • MF: C44H51ClN6O10
  • MW: 859.36
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-PEG4-Val-Cit-PAB

Mal-PEG4-Val-Cit-PAB is a cleavable ADC linker containing a Maleimide group. Mal-PEG4-Val-Cit-PAB is used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1949793-41-2
  • MF: C36H55N7O12
  • MW: 777.86
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DBCO-PEG(4)-NH2

DBCO-NHCO-PEG4-amine is a cleavable ADC linker used to conjugate MMAE (HY-15162) and antibody (e.g., DBCO-VCpAB−MMAE and DBCO-TRX−MMAE with EC50s of 280 nM and 22 nM in SKBR3 cells, respectively)[1].

  • CAS Number: 1255942-08-5
  • MF: C29H37N3O6
  • MW: 523.621
  • Catalog: ADC Linker
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 784.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 428.0±32.9 °C

Azido-PEG5-alcohol

Azido-PEG5-alcohol is a non-cleavable 5 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1]. Azido-PEG5-alcohol is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[2].

  • CAS Number: 86770-68-5
  • MF: C10H21N3O5
  • MW: 263.291
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: 100 °C

Hydroxy-PEG1-acid

Hydroxy-PEG1-acid is a non-cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 89211-34-7
  • MF: C5H10O4
  • MW: 134.13000
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A