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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tans-4-Hydroxy-D-proline methyl ester hydrochloride

tans-4-Hydroxy-D-proline methyl ester hydrochloride is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). tans-4-Hydroxy-D-proline methyl ester hydrochloride is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1][2].

  • CAS Number: 481704-21-6
  • MF: C6H12ClNO3
  • MW: 181.617
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Campathecin

Campathecin is a potent DNA enzyme topoisomerase I inhibitor, with an IC50 of 679 nM.

  • CAS Number: 7689-03-4
  • MF: C20H16N2O4
  • MW: 348.352
  • Catalog: ADC Cytotoxin
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 757.0±60.0 °C at 760 mmHg
  • Melting Point: 260 °C (dec.)(lit.)
  • Flash Point: 411.6±32.9 °C

DTSSP Crosslinker

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

  • CAS Number: 81069-02-5
  • MF: C14H16N2O14S4
  • MW: 564.54200
  • Catalog: ADC Linker
  • Density: 1.94
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Paclitaxel

Paclitaxel is a potent anticancer medication which can promote microtubule (MT) assembly, inhibit MT depolymerization, and change MT dynamics required for mitosis and cell proliferation.

  • CAS Number: 33069-62-4
  • MF: C47H51NO14
  • MW: 853.906
  • Catalog: ADC Cytotoxin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 957.1±65.0 °C at 760 mmHg
  • Melting Point: 213 °C (dec.)(lit.)
  • Flash Point: 532.6±34.3 °C

Glucocorticoid receptor agonist-1 phosphate Gly-Glu-Br

Glucocorticoid receptor agonist-1 phosphate Gly-Glu-Br is an ADC linker that can be used to synthesize ABBV-154, ABBV-927, ABBV-368 or their analogs[1].

  • CAS Number: 2344809-82-9
  • MF: C44H51BrN3O14P
  • MW:
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Docosanedioic acid

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

  • CAS Number: 505-56-6
  • MF: C22H42O4
  • MW: 370.566
  • Catalog: ADC Linker
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 527.0±23.0 °C at 760 mmHg
  • Melting Point: 72-80 °C(lit.)
  • Flash Point: 286.6±19.1 °C

N-Succinimidyl 6-maleimidohexanoate

6-Maleimidohexanoic acid N-hydroxysuccinimide ester(ECMS) is a useful protective group in antibody drug conjugates.

  • CAS Number: 55750-63-5
  • MF: C14H16N2O6
  • MW: 308.287
  • Catalog: ADC Linker
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 480.6±47.0 °C at 760 mmHg
  • Melting Point: 70-73 °C(lit.)
  • Flash Point: 244.5±29.3 °C

Aeruginosin 865

Aeruginosin 865, isolated from terrestrial cyanobacterium Nostoc sp. Lukešová 30/93, is the first aeruginosin-type peptide containing both a fatty acid and a carbohydrate moiety. Aeruginosin 865 inhibits translocation of NF-kB to the nucleus. Aeruginosin 865 has anti-inflammatory effect[1]

  • CAS Number: 1611990-01-2
  • MF: C41H64N6O14
  • MW: 864.98
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-tert-Butoxycarbonyl-trans-4-hydroxy-D-proline

N-tert-Butoxycarbonyl-trans-4-hydroxy-D-proline is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). N-tert-Butoxycarbonyl-trans-4-hydroxy-D-proline is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1][2].

  • CAS Number: 147266-92-0
  • 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: 123ºC
  • Flash Point: 190.2±27.9 °C

diMal-O-CH2COOH

diMal-O-CH2COOH is a cleavable ADC linker.

  • CAS Number: 1620837-47-9
  • MF: C13H12N2O7
  • MW: 308.24
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

INNO-206

Aldoxorubicin (INNO-206) is an albumin-binding prodrug of doxorubicin, which is released from albumin under acidic conditions. Aldoxorubicin (INNO-206) has potent antitumor activities in various cancer cell lines and in in murine tumor models.

  • CAS Number: 1361644-26-9
  • MF: C37H42N4O13
  • MW: 750.748
  • Catalog: ADC Cytotoxin
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MC-GGFG-NH-CH2-O-CH2-cyclopropane-COOH

MC-GGFG-NH-CH2-O-CH2-cyclopropane-COOH is an ADC linker that can be combined with the cytotoxic Camptothecin (HY-16560) to form ADC-related drug-linker conjugates (Drug-Linker Conjugates for ADC ).MC-GGFG-NH-CH2-O-CH2-cyclopropane-COOH is conjugated to Camptothecin, which can further bind to the antibody Trastuzumab (HY-P9907) to form Antibody-Drug Conjugates (ADCs)[1].

  • CAS Number: 2778374-70-0
  • MF: C31H40N6O10
  • MW: 656.68
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CC-885-CH2-PEG1-NH-CH3

CC-885-CH2-PEG1-NH-CH3 is a neoDegrader that can be used in the synthesis of Antibody neoDegrader Conjugate (AnDC)[1][2].

  • CAS Number: 2722698-03-3
  • MF: C26H30ClN5O5
  • MW: 528.00
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Agrochelin

Agrochelin, an alkaloid cytotoxic antibiotic, is produced by the fermentation of a marine Agrobacterium sp. Agrochelin has cytotoxic activity in tumor cell lines[1].

  • CAS Number: 247115-74-8
  • MF: C23H34N2O4S2
  • MW: 466.66
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-PEG7-NHS ester

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

  • CAS Number: 1334170-02-3
  • MF: C26H40N2O15
  • MW: 476.47488
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tubulysin A

Tubulysin A(TubA) is a myxobacterial product that can function as an antiangiogenic agent in many in vitro assays; anti-microtubule, anti-mitotic, an apoptosis inducer, anticancer, anti-angiogenic, and antiproliferative.IC50 value: Target: microtubuleTubulysin A is a novel antibiotic, which is anti-microtubule, anti-mitotic, apoptosis inducer, anticancer, anti-angiogenic, and antiproliferative. Tubulysins are cytotoxic peptides, which include 9 members (A-I). Tubulysin A has potential application as an anticancer agent. It arrests cells in the G2/M phase. Tubulysin A inhibits polymerization more efficiently than vinblastine and induces depolymerization of isolated microtubules. Tubulysin A has potent cytostatic effects on various tumor cell lines with IC50 in the picomolar range.

  • CAS Number: 205304-86-5
  • MF: C43H65N5O10S
  • MW: 844.06900
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG3-maleimide

Azido-PEG3-maleimide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1]. Azido-PEG3-maleimide is also a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[2].

  • CAS Number: 1858264-36-4
  • MF: C15H23N5O6
  • MW: 369.373
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Val-Cit-PAB-OSBT (GMP)

Val-Cit-PAB-OSBT GMP is a GMP grade Val-Cit-PAB-OSBT (HY-78736). Val-Cit-PAB-OSBT is a degradable ADC linker, which is composed of the polypeptide Val-Cit-PAB and OSBT groups coupled together[1].

  • CAS Number: 2210262-26-1
  • MF: C24H43N5O4Si
  • MW: 493.71
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TCO-GK-PEG4-NHS ester

TCO-GK-PEG4-NHS ester is an ADC Linker, and can be used for synthesis of [18F]AlF-NOTA-Tz-TCO-GK-2Rs15d. [18F]AlF-NOTA-Tz-TCO-GK-2Rs15d binds with high affinity and immunoreactivity to HER2[1].

  • CAS Number: 2307311-19-7
  • MF: C33H52N4O14
  • MW: 728.78
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

sulfo-SPDB

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

  • CAS Number: 1193111-39-5
  • MF: C13H14N2O7S3
  • MW: 406.45
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

DBCO acid 2

DBCO acid 2 is a Click Chemistry intermidate used for antibody-drug conjugates.

  • CAS Number: 1207355-31-4
  • MF: C20H17NO3
  • MW: 319.354
  • Catalog: ADC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 635.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 338.2±31.5 °C

H2N-PEG8-CH2CH2COO<sup>t</sup>Bu

Amino-PEG8-Boc is a cleavable 8 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 756526-06-4
  • MF: C23H47NO10
  • MW: 497.62000
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DMAC-SPDB

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

  • CAS Number: 663599-05-1
  • MF: C16H19N3O5S2
  • MW: 397.47
  • 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

sulfo-SPDB-DM4

sulfo-SPDB-DM4 is a drug-linker conjugate for ADC by using the maytansinebased payload (DM4) via the sulfo-SPDB linker.

  • CAS Number: 1626359-59-8
  • MF: C46H63ClN4O17S3
  • MW: 1075.66
  • Catalog: Drug-Linker Conjugates for ADC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Propargyl-PEG3-NHS ester

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

  • CAS Number: 1428629-71-3
  • MF: C14H19NO7
  • MW: 313.303
  • Catalog: ADC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 427.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 212.1±31.5 °C

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