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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SMPT

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

  • CAS Number: 112241-19-7
  • MF: C18H16N2O4S2
  • MW: 388.46100
  • Catalog: ADC Linker
  • Density: 1.43g/cm3
  • Boiling Point: 547ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 284.6ºC

Amino-PEG11-OH

Amino-PEG11-OH is non-cleavable 11 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 15332-94-2
  • MF: C22H47NO11
  • MW: 501.61
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Succinimidyl 3-maleimidopropionate

BMPS is a nonclaevable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).

  • CAS Number: 55750-62-4
  • MF: C11H10N2O6
  • MW: 266.20700
  • Catalog: ADC Linker
  • Density: 1.55g/cm3
  • Boiling Point: 448.8ºC at 760mmHg
  • Melting Point: 168-170 °C(lit.)
  • Flash Point: 225.2ºC

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

β-D-tetraacetylgalactopyranoside-PEG1-N3

β-D-tetraacetylgalactopyranoside-PEG1-N3 is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 153252-36-9
  • MF: C18H27N3O11
  • MW: 461.42
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DBCO-NHCO-PEG4-acid

DBCO-Amide-PEG5-acid is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1870899-46-9
  • MF: C32H40N2O9
  • MW: 596.67
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dolastatin 15

Dolastatin 15 (DLS 15), a depsipeptide derived from Dolabella auricularia, is a potent antimitotic agent structurally related to the antitubulin agent Dolastatin 10. Dolastatin 15 induces cell cycle arrest and apoptosis in multiple myeloma cells. Dolastatin 15 can be used as an ADC cytotoxin[1][2][3].

  • CAS Number: 123884-00-4
  • MF: C45H68N6O9
  • MW: 837.05600
  • Catalog: ADC Cytotoxin
  • Density: 1.2g/cm3
  • Boiling Point: 943.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 524.2ºC

N-Succinimidyl maleimidoacetate

AMAS is a heterobifunctional crosslinker with NHS ester and maleimide groups that allows covalent conjugation of amine- and sulfhydryl-containing molecules.

  • CAS Number: 55750-61-3
  • MF: C10H8N2O6
  • MW: 252.180
  • Catalog: ADC Linker
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 430.1±47.0 °C at 760 mmHg
  • Melting Point: 174-175ºC
  • Flash Point: 213.9±29.3 °C

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

SG2057

SG2057 (DRG16) is a PBD dimer containing a pentyldioxy linkage which binds sequence selectively in the minor groove of DNA forming DNA interstrand and intrastrand cross-linked adducts. SG2057 is a highly active antitumor agent[1].

  • CAS Number: 260417-62-7
  • MF: C33H36N4O6
  • MW: 584.662
  • Catalog: ADC Cytotoxin
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 820.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 449.7±34.3 °C

Glucocorticoid receptor agonist-1 phosphate Gly-Glu TFA

Glucocorticoid receptor agonist-1 phosphate Gly-Glu (TFA) is a cleavable linker, that can be used to synthesize Antibody-Drug Conjugates (ADCs).

  • CAS Number: 2734877-83-7
  • MF: C44H51F3N3O15P
  • MW: 949.86
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aldoxorubicin•HCl

Aldoxorubicin (INNO-206) hydrochloride is an albumin-binding proagent of Doxorubicin (DNA topoisomerase II inhibitor), which is released from albumin under acidic conditions. Aldoxorubicin hydrochloride (INNO-206) has potent antitumor activities in various cancer cell lines and in murine tumor models.

  • CAS Number: 1361563-03-2
  • MF: C37H43ClN4O13
  • MW: 787.21
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CL2 Linker

CL2 Linker is an ADC linker. CL2-SN-38 and CL2A-SN-38 are equivalent in drug substitution (~6), cell binding (Kd ~1.2 nM), cytotoxicity (IC50 ~2.2 nM), and serum stability in vitro (t1/2 ~20 hours)[1][2].

  • CAS Number: 2270986-66-6
  • MF: C68H103N11O22
  • MW: 1426.61
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DMAC-PDB

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

  • CAS Number: 663599-04-0
  • MF: C12H16N2O3S2
  • MW: 300.40
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-PEG5-NHS ester

Bis-PEG5-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 756526-03-1
  • MF: C22H32N2O13
  • MW: 532.49500
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DBCO-N-bis(PEG4-NHS ester)

DBCO-N-bis(PEG4-NHS ester) is a PEG linker which contains two PEG4-NHS ester and a DBCO group. DBCO-N-bis(PEG4-NHS ester) is useful for protein modification or labeling.

  • CAS Number: 2639395-38-1
  • MF: C49H62N4O18
  • MW: 995.03
  • 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

CCK2R Ligand-Linker Conjugates 1

CCK2R ligand CRL is a ligand-linker conjugate; which conjugates to the cytotoxic antimicrotubule agents Desacetyl Vinblastine Hydrazide (DAVBH) and Tubulysin B Hydrazide (TubBH) via a hydrophilic peptide linker[1].

  • CAS Number: 1452145-13-9
  • MF: C72H110N12O27S
  • MW: 1607.77
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Biotin-PEG4-PFP ester

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

  • CAS Number: 1334172-58-5
  • MF: C27H36F5N3O8S
  • MW: 657.647
  • Catalog: ADC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 804.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 440.6±34.3 °C

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

N-Bromoacetyl-β-alanine

N-Bromoacetyl-β-alanine is an alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1]. N-Bromoacetyl-β-alanine is also a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[2].

  • CAS Number: 89520-11-6
  • MF: C5H8BrNO3
  • MW: 210.02600
  • Catalog: ADC Linker
  • Density: 1.682g/cm3
  • Boiling Point: 433.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 215.9ºC

Aminooxy-PEG2-azide

Aminooxy-PEG2-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1]. Aminooxy-PEG2-azide is also a non-cleavable 2 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[2].

  • CAS Number: 1043426-13-6
  • MF: C6H14N4O3
  • MW: 190.20
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Propargyl-PEG4-NHS ester

Propargyl-PEG4-NHS ester is a nonclaevable 4-unit PEG linker for antibody-drug-conjugation (ADC).

  • CAS Number: 1428629-70-2
  • MF: C16H23NO8
  • MW: 357.356
  • Catalog: ADC Linker
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 463.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 233.9±31.5 °C

Mal-VC-PAB-PNP

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

  • CAS Number: 1096584-62-1
  • MF: C32H37N7O11
  • MW: 695.68
  • 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

Azido-PEG8-NHS ester

Azido-PEG8-NHS ester is a cleavable 8 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1]. Azido-PEG8-NHS ester is also a PEG- and Alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs[2].

  • CAS Number: 1204834-00-3
  • MF: C23H40N4O12
  • MW: 564.58300
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-PEG4-Val-Cit-PAB-PNP

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

  • CAS Number: 2112738-09-5
  • MF: C40H53N7O15
  • MW: 871.89
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hydroxy-PEG3-SS-PEG3-alcohol

Hydroxy-PEG3-SS-PEG3-alcohol is also a cleavable 6 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 5662-81-7
  • MF: C16H34O8S2
  • MW: 293.33800
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Me-Tet-PEG2-NHS

Me-Tet-PEG2-NHS is an ADC Linker containing 2 PEG units. Me-Tet-PEG2-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: 2740357-12-2
  • MF: C23H28N6O7
  • MW: 500.50
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A