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.


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Aminoethyl-SS-ethylalcohol

Aminoethyl-SS-ethylalcohol (Compound 3) is an Alkyl-Chain-based PROTAC linker can be used in the synthesis of PROTACs[1]. Aminoethyl-SS-ethylalcohol is also a glutathione cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[2].

  • CAS Number: 15579-01-8
  • MF: C4H11NOS2
  • MW: 153.27
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Boc-Dap-NE

Boc-Dap-NE, a dipeptide, is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).

  • CAS Number: 160800-65-7
  • MF: C23H36N2O5
  • MW: 420.54
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aminoethyl-SS-propionic acid

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

  • CAS Number: 15579-00-7
  • MF: C5H11NO2S2
  • MW: 181.27600
  • Catalog: ADC Linker
  • Density: 1.32g/cm3
  • Boiling Point: 339.5ºC at 760 mmHg
  • Melting Point: 138-141ºC
  • Flash Point: 159.1ºC

4-Succinimidyl-oxycarbonyl-α-(2-pyridyldithio)toluene

4-Succinimidyl-oxycarbonyl-α-(2-pyridyldithio)toluene is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 160854-54-6
  • MF: C17H14N2O4S2
  • MW: 374.43
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DBCO-Sulfo-Link-biotin

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

  • CAS Number: 1363444-70-5
  • MF: C31H35N5O7S2
  • MW: 653.77
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG10-acid

m-PEG10-acid is a non-cleavable 10 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1]. m-PEG10-acid is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[2].

  • CAS Number: 2409969-94-2
  • MF: C22H44O12
  • MW: 500.58
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DC41SMe

DC41-SMe is a DC1 derivative, shows cytotoxicity in Ramos, Namalwa, and HL60/s cells with IC50s ranging from 18-25 pM. DC1, a simplified analogue of CC-1065, is an antibody conjugate of cytotoxic DNA alkylators for the targeted treatment of cancer[1][2].

  • CAS Number: 1354787-71-5
  • MF: C38H36ClN5O4S2
  • MW: 726.31
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hemiasterlin

Hemiasterlin ((-)-Hemiasterlin) is an antimitotic marine natural product with potent anticancer effcts. Hemiasterlin can be used as a cytotoxic payload (ADC Cytotoxin) in antibody-drug conjugates (ADCs)[1].

  • CAS Number: 157207-90-4
  • MF: C30H46N4O4
  • MW: 526.71100
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-PEG17-NHS ester

Bis-PEG17-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2221948-93-0
  • MF: C46H80N2O25
  • MW: 1061.13
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Succinimidyloxycarbonylpropyl methanethiosulfonate

N-Succinimidyloxycarbonylpropyl methanethiosulfonate is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 690632-55-4
  • MF: C9H13NO6S2
  • MW: 295.33300
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azide-SS-biotin

Azide-C2-SS-C2-biotin is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1620523-64-9
  • MF: C14H24N6O2S3
  • MW: 404.57
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

beta-Amanitin

β-Amanitin is a cyclic peptide toxin in the poisonous Amanita phalloides mushroom. β-Amanitin inhibits inhibits eukaryotic RNA polymerase II and III. β-Amanitin inhibits protein synthesis. β-Amanitin can be used as a cytotoxic component of antibody-drug conjugates (ADCs)[1][2].

  • CAS Number: 21150-22-1
  • MF: C39H53N9O15S
  • MW: 919.95400
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG7-Amine

m-PEG7-Amine is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 170572-38-0
  • MF: C15H33NO7
  • MW: 339.42500
  • Catalog: ADC Linker
  • Density: 1.046
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-amido-PEG2-Val-Cit-PAB-PNP

Mal-amido-PEG2-Val-Cit-PAB-PNP is a cleavable 2 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2112738-13-1
  • MF: C39H50N8O14
  • MW: 854.86
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Maytansinol

Maytansinol inhibits microtubule assembly and induces microtubule disassembly in vitro.Target: Microtubule/Tubulinin vitro: Maytansinol disrupts the mitotic spindle and prevents mitotic exit in Drosophila. Maytansinol reduces the growth and/or survival of HCT116 cells in a dose-dependent manner and that the effect was more severe for p53+/+ than for p53-/- cells at both low and high doses. Maytansinol inhibits the growth of HCT116 human colon cancer cells. Maytansinol induces apoptosis in imaginal discs of wild-type larvae but not p53 mutant larvae. This parallels the finding in human HCT116 cells, in which Maytansinol was more effective when p53 was present, at least at some doses. Maytansinol induces apoptosis in imaginal discs of wild-type larvae but not p53 mutant larvae at 24 hours after exposure to drug.

  • CAS Number: 57103-68-1
  • MF: C28H37ClN2O8
  • MW: 565.055
  • Catalog: ADC Cytotoxin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 835.8±65.0 °C at 760 mmHg
  • Melting Point: >153C (dec.)
  • Flash Point: 459.3±34.3 °C

γ-Amanitin

γ-Amanitin an ADC cytotoxin and isolated from the mushroom. γ-Amanitin inhibits RNA polymerase II and disrupts synthesis of mRNA. γ-Amanitin shows similar effects to α-Amanitin (HY-19610) and β-Amanitin (HY-125586)[1].

  • CAS Number: 21150-23-2
  • MF: C39H54N10O13S
  • MW: 902.970
  • Catalog: ADC Cytotoxin
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 1566.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 901.2±34.3 °C

Azido-PEG9-acid

Azido-PEG9-acid is a non-cleavable 9 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).

  • CAS Number: 1670249-37-2
  • MF: C21H41N3O11
  • MW: 511.564
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methyltetrazine-DBCO

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

  • CAS Number: 1802238-48-7
  • MF: C34H33N7O7S
  • MW: 683.73
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DBCO-PEG4-Maleimide

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

  • CAS Number: 1480516-75-3
  • MF: C36H42N4O9
  • MW: 674.740
  • Catalog: ADC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 965.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 537.6±34.3 °C

Seco-DUBA

Seco-DUBA is a duocarmycin (DUBA) prodrug containing two hydroxyl groups, which can each be used for coupling to an antibody via a linker. Seco-DUBA can be used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1227961-59-2
  • MF: C29H23ClN4O4
  • MW: 526.97
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

sulfo-DGN462 sodium

sulfo-DGN462 sodium is degraded to DGN462 in culture medium and plasma. DGN462, a potent DNA-alkylating agent, shows anti-tumor activity, such as acute myeloid leukemia (AML)[1].

  • CAS Number: 1401203-09-5
  • MF: C53H60N5NaO12S2
  • MW: 1046.19
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MMAF

MMAF (Monomethylauristatin F) is an antitubulin agent that inhibit cell division; inhibits H3397 cell growth with an IC50 of 105 nM.

  • CAS Number: 745017-94-1
  • MF: C39H65N5O8
  • MW: 731.962
  • Catalog: ADC Cytotoxin
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 896.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 496.2±34.3 °C

Me-Tet-PEG9-NHS

Me-Tet-PEG9-NHS is an ADC Linker containing 9 PEG units. Me-Tet-PEG9-NHS can utilize its own Tetrazine group to undergo a specific inverse electron demand Diels-Alder reaction (iEDDA) with compounds with TCO groups.

  • CAS Number: 2143955-78-4
  • MF: C36H54N6O14
  • MW: 794.85
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(2-pyridyldithio)-PEG4acid

(2-pyridyldithio)-PEG4 acid is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 581065-93-2
  • MF: C16H25NO6S2
  • MW: 391.50
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cyclooctyne-O-amido-PEG2-PFP ester

Cyclooctyne-O-amido-PEG2-PFP ester is a non-cleavable 2 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2101206-61-3
  • MF: C23H26F5NO6
  • MW: 507.45
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fmoc-Val-Cit-PAB-PNP

Fmoc-Val-Cit-PAB-PNP is a peptide prodrug linker, is a linker for antibody-drug-conjugation (ADC).

  • CAS Number: 863971-53-3
  • MF: C40H42N6O10
  • MW: 766.8
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-MAD-MDCPT

7-MAD-MDCPT, a Camptothecin analog, is a toxin payload in antibody drug conjugates (ADCs)[1].

  • CAS Number: 765871-81-6
  • MF: C22H19N3O6
  • MW: 421.40
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-PEG21-NHS ester

Bis-PEG21-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2221948-98-5
  • MF: C54H96N2O29
  • MW: 1237.34
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fmoc-NH-(PEG)9-CH2CH2COOH

Fmoc-NH-PEG9-CH2CH2COOH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1191064-81-9
  • MF: C36H53NO13
  • MW: 707.805
  • Catalog: ADC Linker
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 803.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 440.0±34.3 °C

Azido-PEG7-amine

Azido-PEG7-amine is a non-cleavable 7 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1333154-77-0
  • MF: C16H34N4O7
  • MW: 394.46400
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A