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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Bis-Tos-(2-hydroxyethyl disulfide)

Bis-Tos-(2-hydroxyethyl disulfide) is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 69981-39-1
  • MF: C18H22O6S4
  • MW: 462.62400
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-Boc-azetidine-3-carboxylic acid

1-Boc-azetidine-3-carboxylic acid is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). 1-Boc-azetidine-3-carboxylic acid is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1][2]

  • CAS Number: 142253-55-2
  • MF: C9H15NO4
  • MW: 201.220
  • Catalog: ADC Linker
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 321.0±35.0 °C at 760 mmHg
  • Melting Point: 100.1-101.9°C
  • Flash Point: 147.9±25.9 °C

SPP

SPP is a disulfide linker, can be used to form cytotoxic compound- linker conjugate[1].

  • CAS Number: 341498-08-6
  • MF: C14H16N2O4S2
  • MW: 340.41800
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DBCO-Maleimide

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

  • CAS Number: 1395786-30-7
  • MF: C25H21N3O4
  • MW: 427.452
  • Catalog: ADC Linker
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 790.5±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 431.9±32.9 °C

Mal-Ala-Ala-PAB-PNP

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

  • CAS Number: 2003260-14-6
  • MF: C30H33N5O10
  • MW: 623.61
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-((S)-2-((S)-2-(6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)propanamido)benzyl (4-nitrophenyl) carbonate

MC-Val-Ala-PAB-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1639939-40-4
  • MF: C32H37N5O10
  • MW: 651.66
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-PEG8-Val-Cit-PAB-MMAE

Mal-PEG8-Val-Cit-PAB-MMAE is a cleavable 8 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2353409-69-3
  • MF: C81H131N11O23
  • MW: 1626.97
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cyclopropaneacetamide-Exatecan

Cyclopropaneacetamide-Exatecan (Compound 2-A) is an ADC Cytotoxin and an Exatecan analogue. Cyclopropaneacetamide-Exatecan can be used in the synthesis of ADC such as anti-B7H3 antibody-Exatecan analogue conjugate (compound ADC-2)[1].

  • CAS Number: 2414254-36-5
  • MF: C29H28FN3O6
  • MW: 533.55
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Me-Tet-PEG8-NHBoc

Me-Tet-PEG8-NHBoc is an ADC Linker containing 8 PEG units. Me-Tet-PEG8-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: 2143968-21-0
  • MF: C34H56N6O11
  • MW: 724.84
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-2-((S)-2-amino-3-methylbutanamido)-5-ureidopentanoic acid

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

  • CAS Number: 159858-33-0
  • MF: C11H22N4O4
  • MW: 274.32
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MC-Val-Cit-PAB-tubulysin5a

MC-Val-Cit-PAB-tubulysin5a 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-tubulysin5a 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: 2055896-86-9
  • MF: C66H96N11O13S
  • MW: 1283.60
  • Catalog: Drug-Linker Conjugates for ADC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Propargyl-PEG2-amine

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

  • CAS Number: 944561-44-8
  • MF: C7H13NO2
  • MW: 143.18400
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG6-Amine

m-PEG6-Amine is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 184357-46-8
  • MF: C13H29NO6
  • MW: 295.37200
  • Catalog: ADC Linker
  • Density: 1.036
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MC-Val-Cit-PAB-clindamycin

MC-Val-Cit-PAB-clindamycin 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-clindamycin 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: 1639793-13-7
  • MF: C46H72ClN8O11S
  • MW: 980.63
  • Catalog: Drug-Linker Conjugates for ADC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG6-NHS ester

Azido-PEG6-NHS ester is a cleavable 6 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1]. Azido-PEG6-NHS ester is also a PEG- and Alkyl/ether based PROTAC linker that can be used in the synthesis of PROTACs[2].

  • CAS Number: 2055014-64-5
  • MF: C19H32N4O10
  • MW: 476.48
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Biotin-PEG1-azide

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

  • CAS Number: 1204085-48-2
  • MF: C14H24N6O3S
  • MW: 356.44400
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Taltobulin trifluoroacetate

Taltobulin trifluoroacetate (HTI-286; SPA-110) is an analogue of Hemiasterlin; potent tubulin inhibitor; ADCs cytotoxin.IC50 value:Target: tubulinin vitro: HTI-286 significantly inhibited proliferation of all three hepatic tumor cell lines (mean IC50 = 2 nmol/L +/- 1 nmol/L) in vitro. Interestingly, no decrease in viable primary human hepatocytes (PHH) was detected under HTI-286 exposure [1]. In all cell lines tested, HTI-286 was a potent inhibitor of proliferation and induced marked increases in apoptosis. Despite similar transcriptomic changes regarding cell death and cell cycle regulating genes after exposure to HTI-286 or docetaxel, array analysis revealed distinct molecular signatures for both compounds [2].in vivo: Intravenous administration of HTI-286 significantly inhibited tumor growth in vivo (rat allograft model) [1]. HTI-286 significantly inhibited growth of PC-3 and LNCaP xenografts and retained potency in PC-3dR tumors. Simultaneous castration plus HTI-286 therapy was superior to sequential treatment in the LNCaP model [2].

  • CAS Number: 228266-41-9
  • MF: C29H44F3N3O6
  • MW: 587.671
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fmoc-NH-PEG6-CH2CH2COOH

Fmoc-NH-PEG6-CH2CH2COOH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 882847-34-9
  • MF: C30H41NO10
  • MW: 575.64700
  • Catalog: ADC Linker
  • Density: 1.202±0.06 g/cm3 (20ºC 760 Torr)
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Piericidin A1

Piericidin A (AR-054) is a natural mitochondrial NADH-ubiquinone oxidoreductase (complex I) inhibitor. Piericidin A is a potent neurotoxin and inhibits mitochondrial respiration by disrupting the electron transport system through its action on NADH-ubiquinone reductase. Piericidin A is also a potential quorum-sensing inhibitor that suppresses the expression of the virulence genes of Erwinia carotovora subsp. atroseptica (Eca). Piericidin A is an ADC cytotoxin and has anti-bacterial, anticancer, insecticidal activity[1][2][2].

  • CAS Number: 2738-64-9
  • MF: C25H37NO4
  • MW: 415.566
  • Catalog: Bacterial
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 591.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 311.6±30.1 °C

N-Boc-cis-4-Hydroxy-D-proline

N-Boc-cis-4-Hydroxy-D-proline is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). N-Boc-cis-4-Hydroxy-D-proline is also a alkyl chain-based PROTAC linker that can be used in the synth

  • CAS Number: 135042-12-5
  • 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: 145ºC
  • Flash Point: 190.2±27.9 °C

Me-Tet-PEG4-NHS

Me-Tet-PEG4-NHS is an ADC Linker containing 4 PEG units. Me-Tet-PEG4-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: 2143968-22-1
  • MF: C26H34N6O9
  • MW: 574.58
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MC-Val-Cit-PAB-Retapamulin

MC-Val-Cit-PAB-retapamulin 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-retapamulin 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: 1639793-15-9
  • MF: C58H86N7O10S
  • MW: 1073.41
  • Catalog: Drug-Linker Conjugates for ADC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-N-Boc-3-hydroxyazetidine

1-N-Boc-3-hydroxyazetidine is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). 1-N-Boc-3-hydroxyazetidine is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs

  • CAS Number: 141699-55-0
  • MF: C8H15NO3
  • MW: 173.210
  • Catalog: ADC Linker
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 253.7±33.0 °C at 760 mmHg
  • Melting Point: 42-44°C
  • Flash Point: 107.2±25.4 °C

DBCO-NHCO-PEG4-NHS ester

DBCO-NHCO-PEG4-NHS ester ester is a MMP-2- and cathepsin B- (CatB) cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2100306-58-7
  • MF: C34H39N3O10
  • MW: 649.69
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Boc-NH-PEG1-CH2CH2COOH

Boc-NH-PEG1-CH2CH2COOH is a cleavable (1 unit PEG) ADC linker and also a PEG- and Alkyl/ether-based PROTAC linker can be used in the synthesis of antibody-drug conjugates (ADCs) or PROTACs[1][2].

  • CAS Number: 1260092-44-1
  • MF: C10H19NO5
  • MW: 233.262
  • Catalog: ADC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 385.0±27.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 186.7±23.7 °C

Azide-C2-Azide

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

  • CAS Number: 629-13-0
  • MF: C2H4N6
  • MW: 112.09300
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Me-Tet-PEG2-COOH

Me-Tet-PEG2-COOH is an ADC Linker containing 2 PEG units. Me-Tet-PEG2-COOH can use its own Tetrazine group to undergo a specific inverse electron demand Diels-Alder reaction (iEDDA) with compounds with TCO groups.

  • CAS Number: 2741759-99-7
  • MF: C18H23N5O5
  • MW: 389.41
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-PEG9-NHS ester

Bis-PEG9-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1008402-79-6
  • MF: C30H48N2O17
  • MW: 708.70500
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Boc-cis-4-hydroxy-D-proline methyl ester

N-Boc-cis-4-hydroxy-D-proline methyl ester is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). N-Boc-cis-4-hydroxy-D-proline methyl ester is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1

  • CAS Number: 114676-69-6
  • MF: C11H19NO5
  • MW: 245.27200
  • Catalog: ADC Linker
  • Density: 1.216g/cm3
  • Boiling Point: 335.2ºC at 760mmHg
  • Melting Point: 80 °C
  • Flash Point: 156.6ºC

Boc-trans-D-Hyp-OMe

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

  • CAS Number: 135042-17-0
  • MF: C11H19NO5
  • MW: 245.272
  • Catalog: ADC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 387.6±42.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 188.2±27.9 °C