A cytotoxic agent used in antibody-drug conjugates

A drug-linker conjugate for Antibody-drug conjugates (ADCs) by using the anti-mitotic agent, monomethyl auristatin E (MMAE), linked via the cleavable peptide Val-Cit-PAB..

A novel potent DNA-intercalating payload dimer (PBD dimer) payload for antibody-drug conjugates (ADCs).

MMAF-Ome belongs to ADC, and inhibits several tumor cell lines with IC50s of 0.056 nM, 0.166 nM, 0.183 nM, and 0.449 nM for MDAMB435/5T4, MDAMB361DYT2, MDAMB468, and Raji (5T4-) cell lines, respectively.

Maytansinol inhibits microtubule assembly and induces microtubule disassembly in vitro. Target: Microtubule/Tubulin in vitro: Maytansinol disrupts the mitotic spindle and prevents mitotic exit in Drosophila. Maytansinol reduces the growth and/or survival of HCT116 cells in a dose-dependent manner and that the effect was more severe for p53+/+ than for p53-/- cells at both low and high doses. Maytansinol inhibits the growth of HCT116 human colon cancer cells. Maytansinol induces apoptosis in imaginal discs of wild-type larvae but not p53 mutant larvae. This parallels the finding in human HCT116 cells, in which Maytansinol was more effective when p53 was present, at least at some doses. Maytansinol induces apoptosis in imaginal discs of wild-type larvae but not p53 mutant larvae at 24 hours after exposure to drug.

Ansamitocin P-3, a potent anti-tumor maytansinoid found in Actinosynnema pretiosum, is a maytansine analog which displays potent cytotoxicity against the human solid tumor cell lines A-549 and HT-29.

Calicheamicin, also known as Calicheamicin gamma(1,I) or Calichemicin gamma1, is an potent enediyne antitumor antibiotics derived from the bacterium Micromonospora echinospora. Calicheamicin targets DNA and cause strand scission. Calicheamicin binds with DNA in the minor groove, wherein it then undergos a reaction analogous to the Bergman cyclization to generate a diradical species. This diradical, 1,4-didehydrobenzene, then abstracts hydrogen atoms from the deoxyribose (sugar) backbone of DNA, which ultimately leads to strand scission. The specificity of binding of calicheamicin to the minor groove of DNA is due to the aryltetrasaccharide group of the molecule.

Daun02 is a daunorubicin b-galactoside prodrug for use in conjunction.

Daunorubicin HCl inhibits both DNA and RNA synthesis and inhibits DNA synthesis with Ki of 0.02 μM.

DM1-SMCC is DM1 with a reactive linker SMCC, which can react with antibody to make antibody drug conjugate.

Fmoc-Val-Cit-PAB is a linker for antibody-drug-conjugation (ADC).

Fmoc-Val-Cit-PAB-PNP is a peptide prodrug linker, is a linker for antibody-drug-conjugation (ADC).

MC-Val-Cit-PAB, also known as MC-Val-Cit-PAB-OH, is a cathepsin cleavable ADC peptide linker. MC-Val-Cit-PAB is useful for making ADC conjugate (antibody-drug conjugate). FDA approved drugs such as brentuximab vedotin used this linker.

Mc-Val-Cit-PABC-PNP is a cathepsin cleavable ADC peptide linker. For example, FDA approved drug, brentuximab vedotin, adopts this linker.

N3-PEG3-vc-PAB-MMAE is a drug-linker conjugate for ADC with potent antitumor activity by using the anti-mitotic agent, monomethyl auristatin E (MMAE), linked via the peptide N3-PEG3-vc-PAB.

OSW-1 is a natural anti-enterovirus and anti-cancer compound that targets oxysterol-binding protein (OSBP) with Ki of 26 and 54 nM for OSBP and ORP4L, respectively.

PNU-159682 is a major bioactive metabolite of Nemorubicin in human liver microsomes; > 3,000-fold cytotoxic than its parent compound(MMDX and doxorubicin).

SG3199 is a PBD dimer warhead component of antibody-drug conjugate (ADC) payload tesirine, demonstrates potently cytotoxic against a panel of human solid tumour and haematological cancer cell lines with mean GI50 of 151.5 pM.

SGD-1882 (PBD dimer, Pyrrolobenzodiazepine dimer) is a novel potent DNA-intercalating payload dimer (PBD dimer) payload for antibody-drug conjugates (ADCs)..

Tesirine ( SG3249) is a cathepsin B-cleavable valine-alanine pyrrolobenzodiazepine (PBD) dimer as antibody-drug conjugate (ADC) payload.

Monomethyl auristatin E (MMAE; Vedotin) is a hot topic in Antibody-drug conjugates (ADCs) studies. It is an antimitotic agent which inhibits cell division by blocking the polymerisation of tubulin.

Maytansine, a benzoansamacrolide, is a highly potent microtubule-targeted compound that induces mitotic arrest and kills tumor cells at subnanomolar concentrations. However, it failed as an anticancer agent in human clinical trials because of lack of tumo