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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MMAF (Hydrochloride)

MMAF hydrochloride is an antitubulin agent that inhibit cell division; inhibits H3397 cell growth with an IC50 of 105 nM.

  • CAS Number: 1415246-68-2
  • MF: C39H66ClN5O8
  • MW: 768.42300
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

m-PEG3-Amine

m-PEG3-Amine is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 74654-07-2
  • MF: C7H17NO3
  • MW: 163.21500
  • Catalog: ADC Linker
  • Density: 0.978g/cm3
  • Boiling Point: 223.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 86.1ºC

Succinic anhydride

Succinic anhydride is a cyclic anhydride and an ADC linker extracted from patent WO2009064913A1. It can react with compound 4 of the patent to link the prodrug to an amine or hydroxy 1 group of a targeting polypeptide[1].

  • CAS Number: 108-30-5
  • MF: C4H4O3
  • MW: 100.073
  • Catalog: ADC Linker
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 261.0±0.0 °C at 760 mmHg
  • Melting Point: 118-120 °C(lit.)
  • Flash Point: 122.1±15.9 °C

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

Azidoethyl-SS-propionic acid

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

  • CAS Number: 2228857-32-5
  • MF: C5H9N3O2S2
  • MW: 207.27
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Propargyl-PEG6-NHS ester

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

  • CAS Number: 2093153-99-0
  • MF: C20H31NO10
  • MW: 445.46
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fmoc-N-(2-Boc-aminoethyl)-Gly-OH

Fmoc-N-(2-Boc-aminoethyl)-Gly-OH is a Fmoc-protected glycine derivative that can be used in antibody drug coupling (ADC) synthesis. ADC consists of antibodies that are linked to ADC cytotoxins via ADC junctions[1].

  • CAS Number: 141743-15-9
  • MF: C24H28N2O6
  • MW: 440.48900
  • Catalog: ADC Linker
  • Density: 1.25 g/cm3
  • Boiling Point: 638.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 339.8ºC

Tetraethylene glycol monotosylate

Tetraethylene glycol monotosylate is a cleavable and acylhydrazone-based ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 77544-60-6
  • MF: C15H24O7S
  • MW: 348.41200
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Boc-Val-Cit-PAB-PNP

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

  • CAS Number: 870487-10-8
  • MF: C30H40N6O10
  • MW: 644.6728
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG8-Amine

m-PEG8-Amine is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 869718-81-0
  • MF: C17H37NO8
  • MW: 383.47800
  • Catalog: ADC Linker
  • Density: 1.054
  • Boiling Point: 448ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 213.9ºC

Maytansinoid dM4

Maytansinoid DM4 is a thiol-containing maytansine derivative with highly potent cytotoxicity. Maytansinoid DM4 can be used as a cytotoxic moiety of ADC[1][2].

  • CAS Number: 799840-96-3
  • MF: C39H56ClN3O10S
  • MW: 794.394
  • Catalog: ADC Cytotoxin
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 940.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 522.4±34.3 °C

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

Aminooxy-PEG4-alcohol

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

  • CAS Number: 106492-60-8
  • MF: C8H19NO5
  • MW: 209.24000
  • 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

Amino-ethyl-SS-PEG3-NHBoc

Amino-ethyl-SS-PEG3-NHBoc is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2144777-87-5
  • MF: C15H32N2O5S2
  • MW: 384.55
  • 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

Boc-Hyp-OMe

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

  • CAS Number: 74844-91-0
  • MF: C11H19NO5
  • MW: 245.272
  • Catalog: ADC Linker
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 335.2±42.0 °C at 760 mmHg
  • Melting Point: 92-96 °C(lit.)
  • Flash Point: 156.6±27.9 °C

Gly-Gly-Gly-PEG4-methyltetrazine

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

  • CAS Number: 2353409-82-0
  • MF: C23H34N8O7
  • MW: 534.57
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azidoethyl-SS-propionic NHS ester

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

  • CAS Number: 2243566-44-9
  • MF: C9H12N4O4S2
  • MW: 304.35
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fmoc-NH-ethyl-SS-propionic NHS ester

Fmoc-NH-ethyl-SS-propionic NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2128735-23-7
  • MF: C24H24N2O6S2
  • MW: 500.59
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Puwainaphycin F

Puwainaphycin F, a cyanobacterial cyclic lipopeptide, is a moderate cytotoxin isolated from the soil cyanobacterium Cylindrospermum alatosporum C24/89. Puwainaphycin F causes necrotic cell death to mammalian cells via cell membrane permeabilization and subsequent unusual actin relocalization[1].

  • CAS Number: 1379577-47-5
  • MF: C53H87N13O15
  • MW: 1146.34
  • Catalog: ADC Cytotoxin
  • 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

m-C-tri(CH2-PEG1-NHSester)

m-C-tri(CH2-PEG1-NHS ester) is a non-cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 173414-89-6
  • MF: C26H33N3O15
  • MW: 627.55
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Doxorubicin Hydrochloride

Doxorubicin hydrochloride is a cytotoxic anthracycline antibiotic for the treatment of multiple cancers. The possible mechanisms by which doxorubicin acts in the cancer cell are intercalation into DNA and disruption of topoisomerase-II-mediated DNA repair.

  • CAS Number: 25316-40-9
  • MF: C27H30ClNO11
  • MW: 579.980
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: 810.3ºC at 760 mmHg
  • Melting Point: 216ºC
  • Flash Point: 443.8ºC

alpha-Amanitin

alpha-Amanitin is the principal toxin of several deadly poisonous mushrooms, exerting its toxic function by inhibiting RNA-polymerase II.

  • CAS Number: 23109-05-9
  • MF: C39H54N10O14S
  • MW: 918.97000
  • Catalog: ADC Cytotoxin
  • Density: 1.57 g/cm3
  • Boiling Point: 1622.2ºC at 760 mmHg
  • Melting Point: 254-255ºC(lit.)
  • Flash Point: 934.9ºC

Tup hydrochloride

Tup hydrochloride is a cleavable ADC linker.

  • CAS Number: 1200041-11-7
  • MF: C12H18ClNO3
  • MW: 259.73
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG5-CH2CO2H

Azido-PEG5-CH2CO2H is a cleavable 5 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 217180-81-9
  • MF: C12H23N3O7
  • MW: 321.327
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azidoethyl-SS-ethylamine

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

  • CAS Number: 1807512-40-8
  • MF: C4H10N4S2
  • MW: 178.28
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A