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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DBCO-PEG4-DBCO

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

  • CAS Number: 2182601-68-7
  • MF: C48H50N4O8
  • MW: 810.93
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-sulfone-PEG3-Azide

Bis-sulfone-PEG3-Azide is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).

  • CAS Number: 1802908-01-5
  • MF: C33H40N4O9S2
  • MW: 700.82
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Monomethyl auristatin E

Monomethyl auristatin E (MMAE) is a synthetic derivative of dolastatin 10 and functions as a potent mitotic inhibitor by inhibiting tubulin polymerization. MMAE is widely used as a cytotoxic component of antibody-drug conjugates (ADCs) to treat several different cancer types.

  • CAS Number: 474645-27-7
  • MF: C39H67N5O7
  • MW: 717.979
  • Catalog: ADC Cytotoxin
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 873.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 482.1±34.3 °C

(2S,4S)-1-tert-Butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate

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

  • CAS Number: 102195-79-9
  • 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: 82-86ºC
  • Flash Point: 156.6±27.9 °C

DBCO-​C6-​acid

DBCO-C6-acid is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-C6-acid can be used in the synthesis of carmaphycin analogues[1].

  • CAS Number: 1425485-72-8
  • MF: C21H19NO3
  • MW: 333.380
  • Catalog: ADC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 634.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 337.5±31.5 °C

Amino-PEG9-acid

Amino-PEG9-acid is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1191079-83-0
  • MF: C21H43NO11
  • MW: 485.566
  • Catalog: ADC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 578.3±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 303.6±30.1 °C

6-Azido-hexylamine

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

  • CAS Number: 349553-73-7
  • MF: C6H14N4
  • MW: 142.20200
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SPDP-dPEG

LC-PEG8-SPDP is a cleavable ADC linker used for the antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1252257-56-9
  • MF: C31H49N3O13S2
  • MW: 735.863
  • Catalog: ADC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fmoc-NH-PEG2-CH2CH2COOH

Fmoc-NH-PEG2-CH2CH2COOH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 872679-70-4
  • MF: C22H25NO6
  • MW: 399.437
  • Catalog: ADC Linker
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 622.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 330.0±31.5 °C

Paclitaxel-d5

Paclitaxel D5 is a deuterium-labeled Paclitaxel. Paclitaxel is a naturally occurring antineoplastic agent and stabilizes tubulin polymerization[1].

  • CAS Number: 1129540-33-5
  • MF: C47H46D5NO14
  • MW: 858.93700
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fmoc-MMAE

Fmoc-MMAE is a protective group-conjugated monomethyl auristatin E (MMAE), which is a potent tubulin inhibitor. Fmoc-MMAE can be used in the synthesis of ADC[1].

  • CAS Number: 474645-26-6
  • MF: C54H77N5O9
  • MW: 940.22
  • Catalog: ADC Cytotoxin
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 1036.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 580.6±34.3 °C

Hydroxy-PEG2-(CH2)2-Boc

Hydroxy-PEG2-(CH2)2-Boc is a uncleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Hydroxy-PEG2-(CH2)2-Boc is extracted from patent WO2004008101A2 (compound 196)[1].

  • CAS Number: 133803-81-3
  • MF: C11H22O5
  • MW: 234.28900
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG4-C2-acid

Azido-PEG4-C2-acid a PEG-based PROTAC linker can be used in the synthesis of vRucaparib-TP4. Azido-PEG4-C2-acid is also a non-cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).

  • CAS Number: 1257063-35-6
  • MF: C11H21N3O6
  • MW: 291.30100
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PNU-159682

PNU-159682, a highly potent metabolite of the anthracycline nemorubicin with outstanding cytotoxicity, is a potent ADCs cytotoxin.

  • CAS Number: 202350-68-3
  • MF: C32H35NO13
  • MW: 641.619
  • Catalog: ADC Cytotoxin
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 838.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 460.9±34.3 °C

rel-1-((1R,8S,9s)-Bicyclo[6.1.0]non-4-yn-9-yl)-3-oxo-2,7,10,13,16-pentaoxa-4-azanonadecan-19-oic acid

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

  • CAS Number: 1881221-47-1
  • MF: C22H35NO8
  • MW: 441.52
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

vc-PAB-DMEA-PNU159682

vc-PAB-DMEA-PNU159682 (compound I.47) can be used to synthesize the ADC molecule based on Sulfomaleimide-based Linker. vc-PAB-DMEA-PNU159682 has good serum stability[1].

  • CAS Number: 2227350-96-9
  • MF: C56H72N8O19
  • MW: 1161.21
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NMS-P528

NMS-P528 is a Duocarmycin derivative that can be used as an ADC payload. NMS-P528 can be used to synthesize NMS-P945[1].

  • CAS Number: 1466546-45-1
  • MF: C27H28ClN3O3S
  • MW: 510.05
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

THP-PEG7

THP-PEG6-OH is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1]. THP-PEG6-OH is also a non-cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[2].

  • CAS Number: 42607-87-4
  • MF: C17H34O8
  • MW: 232.23900
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TKN87180

TKN87180 is a Hydrolyzable linker for making ADC conjugate. TKN87180 was first reported in Bioorganic & Medicinal Chemistry Letters (2004), 14(16), 4323-4327. This product has not formal name. For the convenience of scientific communication, we named it by combining its Inchi key (3 letters from the first letter of each section) with the last 5 digits of its CAS number or its molecule weight if its CAS number is not available.

  • CAS Number: 756487-18-0
  • MF: C37H49N5O8
  • MW: 691.826
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CL2A-SN-38

CL2A-SN-38, SN-38 (topoisomerase-I inhibitor) derivative, is a peptide linker. CL2A-SN-38 is conjugated to the anti-Trop-2-humanized antibody, SN-38-anti-Trop-2 antibody-drug conjugate (ADC) against several human solid tumor types, provides significant and specific antitumor effects against a range of human solid tumor types[1].

  • CAS Number: 1279680-68-0
  • MF: C73H97N11O22
  • MW: 1480.61
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Boc-Val-Ala-PAB-PNP

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

  • CAS Number: 1884578-00-0
  • MF: C27H34N4O9
  • MW: 558.58
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MC-Val-Ala-OH

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

  • CAS Number: 1342211-31-7
  • MF: C18H27N3O6
  • MW: 381.42
  • Catalog: ADC Linker
  • Density: 1.232±0.06 g/cm3(Predicted)
  • Boiling Point: 695.4±50.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

N-Boc-PEG6-alcohol

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

  • CAS Number: 331242-61-6
  • MF: C17H35NO8
  • MW: 381.46200
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Py-MAA-Val-Cit-PAB-MMAE

Py-MAA-Val-Cit-PAB-MMAE (AAJ8D6-PY-Val-Cit-MMAE) is an ADC Linker of Zapadcine-3a. Zapadcine-3a is an anti-TRAILR2 ADC with broad spectrum, and antineoplastic effect. Zapadcine-3a can be swallowed up into lysosome of tumor cells by binding to TRAILR2. Then Zapadcine-3a releases small molecular compound to specifically kill various TRAILR2-pos. Zapadcine-3a potently eradicates tumor cells and cures tumor[1].

  • CAS Number: 2247398-68-9
  • MF: C72H111N13O16S
  • MW: 1446.79
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DC41

DC41 is a DC1 derivative. 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: 1354787-69-1
  • MF: C37H34ClN5O4S
  • MW: 680.21
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

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

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

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