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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FBN33428

FBN33428, also known as Fmoc-​Phe-​Lys(Boc)​-​PAB; is a Hydrolyzable linker for making ADC conjugate. FBN33428 is useful for mkaing hydrolyzable prodrugs for delivery of anticancer drugs to metastatic cells. FBN33428 was first reported in WO 9813059. 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: 206133-42-8
  • MF: C42H48N4O7
  • MW: 720.867
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Boc-C16-COOH

Boc-C16-COOH is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Boc-C16-COOH is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs[1]

  • CAS Number: 843666-40-0
  • MF: C22H42O4
  • MW: 370.56600
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Calicheamicin

Calicheamicin is a cytotoxic agent that causes double-strand DNA breaks.

  • CAS Number: 108212-75-5
  • MF: C55H74IN3O21S4
  • MW: 1368.348
  • Catalog: ADC Cytotoxin
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-PEG10-NHS ester

Bis-PEG10-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2221949-02-4
  • MF: C32H52N2O18
  • MW: 752.76
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

gmbs

GMBS is a heterobifunctional cross-linker. GMBS is often used to prepare antibody-enzyme and hapten-carrier protein conjugates.

  • CAS Number: 80307-12-6
  • MF: C12H12N2O6
  • MW: 280.233
  • Catalog: ADC Linker
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 461.3±47.0 °C at 760 mmHg
  • Melting Point: 123-129ºC
  • Flash Point: 232.8±29.3 °C

S-Me-DM4

S-Me-DM4 is a metabolite of DM4 S-methylated by intracellular enzyme. DM4 (HY-100503) is a microtubule-depolymerizing maytansinoid with strong cytotoxicity. DM4 can be used as an ADC Cytotoxin molecule[1].

  • CAS Number: 890654-03-2
  • MF: C39H56ClN3O10S
  • MW: 794.39
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azido-PEG3-Val-Cit-PAB-OH

Azido-PEG3-Val-Cit-PAB-OH is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 2055024-65-0
  • MF: C27H44N8O8
  • MW: 608.69
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BCN-HS-PEG2-VA-PABC-SG3199

BCN-HS-PEG2-VA-PABC-SG3199 (Compound 4) is a pyrrolobenzodiazepine that can be used as a drug linker of antibody-drug conjugates (ADC)[1].

  • CAS Number: 2126805-05-6
  • MF: C66H83N9O18S
  • MW: 1322.48
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Propargyl-PEG8-NHS ester

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

  • CAS Number: 2182601-74-5
  • MF: C24H39NO12
  • MW: 533.57
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

bisSP1

bisSP1 is an antibody drug conjugates linker[1].

  • CAS Number: 2253947-15-6
  • MF: C12H23N9O2
  • MW: 325.37
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ald-Ph-amido-PEG4-propargyl

Ald-Ph-amido-PEG4-propargyl is a non-cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1969299-27-1
  • MF: C19H25NO6
  • MW: 363.40
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DBCO-PEG3 acetic-EVCit-PAB

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

  • CAS Number: 2253947-17-8
  • MF: C54H72N8O13
  • MW: 1041.20
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fomc-Gly-Gly-Phe-Gly-OH

Fomc-Gly-Gly-Phe-Gly-OH (compound D5) can be used as an intermediate in the synthesis of ADC dual-drug-linker. Fomc-Gly-Gly-Phe-Gly-OH synthetic intermediate GGFGE further forms an important ADC dual-drug link assembly unit[1].

  • CAS Number: 1817857-75-2
  • MF: C30H30N4O7
  • MW: 558.58
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vipivotide tetraxetan Linker

Vipivotide tetraxetan Linker is a useful peptide linker for synthesis of Vipivotide tetraxetan (PSMA-617). Vipivotide tetraxetan (PSMA-617) is a ligand used to synthesize 177Lu-PSMA-617, which is a radioactive molecule for the treatment of prostate cancer[1].

  • CAS Number: 1703768-74-4
  • MF: C33H45N5O9
  • MW: 655.74
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m-PEG3-CH2CH2COOH

m-PEG3-CH2CH2COOH is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).

  • CAS Number: 67319-28-2
  • MF: C10H20O6
  • MW: 236.262
  • Catalog: ADC Linker
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 352.3±32.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 129.8±18.6 °C

NMS-P945

NMS-P945 is an ADC linker that can be used in the synthesis of antibody-drug conjugates (ADCs). NMS-P945 is suitable for conjugation to mAbs with reproducible Drug Antibody Ratio (DAR) >3.5[1].

  • CAS Number: 1466546-35-9
  • MF: C61H76ClN11O12S
  • MW: 1222.84
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Maleimido-tri(ethylene glycol)-propionic acid

Maleimido-tri(ethylene glycol)-propionic acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Maleimido-tri(ethylene glycol)-propionic acid is used for the preparation of neolymphostin-based ADC precursors for site-specific cysteine mutant trastuzumab-A114C conjugation[1].

  • CAS Number: 518044-40-1
  • MF: C13H19NO7
  • MW: 301.293
  • Catalog: ADC Linker
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 634.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 337.3±31.5 °C

N-Boc-PEG4-bromide

N-Boc-PEG5-bromide is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs)[1].

  • CAS Number: 1392499-32-9
  • MF: C15H30BrNO6
  • MW: 400.31
  • Catalog: ADC Linker
  • Density: 1.223±0.06 g/cm3
  • Boiling Point: 459.3±40.0 °C
  • Melting Point: N/A
  • Flash Point: N/A

UAA crosslinker 1

UAA crosslinker 1 act as substrates for pylRS/tRNA pair that enable its incorporation into a target protein.

  • CAS Number: 1167421-25-1
  • MF: C9H17N5O4
  • MW: 259.26200
  • Catalog: ADC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2',3'-cGAMP-C2-SH

2',3'-cGAMP-C2-SH is a ADC cytotoxin that is extracted from patent US20210015941, example 24[1].

  • CAS Number: 2133823-39-7
  • MF: C22H28N10O12P2S
  • MW: 718.53
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

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

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

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

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

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

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

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