ADC Cytotoxin

Paclitaxel (Taxol) is a natural product and a microtubule polymer stabilizer. Paclitaxel has anti-tumor activity and causes cell death by inducing mitotic arrest, apoptosis, and cell autophagy.

Mertansine (DM1) refers to the thiol-containing maytansinoid, DM1 (N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine) attached to a monoclonal antibody through reaction of the thiol group with the SPP (N-succinimidyl 4-(2-pyridyldithio)) linker to create an antibody-drug conjugate or ADC. Experimental ADCs with the SPP-DM1 design include lorvotuzumab mertansine.

Doxorubicin hydrochloride (Adriamycin) belongs to the anthracycline class of antibiotics and is an inhibitor of human DNA topoisomerase I II (IC50=0.8 2.67 μM). Doxorubicin hydrochloride exhibits cytotoxicity and antitumor activity. Doxorubicin hydrochloride reduces the phosphorylation of AMPK and its downstream target protein acetyl coenzyme A carboxylase, and induces apoptosis and autophagy.

Duocarmycin TM is a DNA alkylator. Duocarmycin TM is an exceptionally potent antitumor antibiotic.

Dexamethasone (Hexadecadrol) is a glucocorticoid receptor agonist and IL receptor modulator with anti-inflammatory and immunosuppressive properties that induces autophagy and inhibits LPS-induced inflammatory responses in macrophages.

Exatecan (DX-8951f) is a DNA topoisomerase I (TOP1) inhibitor with an IC50 value of 2.2 μM (0.975 μg/mL).Exatecan has antitumor activity and may be used in cancer research.

Dxd (OQM5SD32BQ) is a potent inhibitor of DNA topoisomerase I with an IC50 of 0.31 μM. It is used as a conjugated drug of HER2-targeting ADC.

Aldoxorubicin hydrochloride is an albumin-binding prodrug of Doxorubicin, a DNA topoisomerase II inhibitor. Aldoxorubicin hydrochloride is released from albumin under acidic conditions. Aldoxorubicin hydrochloride exhibits potent antitumor activities in various cancer cell lines and in murine tumor models.

Methotrexate (WR19039) is a folate analog, an inhibitor of the dihydrofolate reductase DHFR. Methotrexate has antimetabolic, antitumor, and immunosuppressive activities, and is commonly used in rheumatoid arthritis and various tumors.

SN-38 (NK012) is the active metabolite of Irinotecan, a DNA topoisomerase I (Topo I) inhibitor, which inhibits DNA and RNA synthesis (IC50=0.077/1.3 μM). SN-38 has antitumor activity and induces autophagy.

Daunorubicin hydrochloride (Rubidomycin hydrochloride), an anthracycline aminoglycoside antineoplastic, inhibits DNA replication and repair and RNA and protein synthesis.

DRF-1042, an orally active camptothecin analog, exhibits anticancer and insecticidal activities by inhibiting DNA topoisomerase I. It has been studied for its efficacy against solid tumors, including prostate and colon cancers.

SG2057 (DRG16), a potent antitumor agent, is a pyrrolobenzodiazepine (PBD) dimer connected by a pentyldioxy linkage. This compound selectively binds to the minor groove of DNA, forming both interstrand and intrastrand cross-linked adducts, contributing to its high antitumor activity.

MMAF (MonoMethyl auristatin F), an antimitotic agent, inhibits cell division by blocking the polymerization of tubulin.

Camptothecin (CPT) belongs to the alkaloid group of natural products and is a specific DNA topoisomerase I (Topo I) inhibitor (IC50=679 nM) with specificity. Camptothecin has antitumor activity and induces apoptosis.

DM4 (Ravtansine) can be used in the preparation of antibody drug conjugate and it is an antitubulin agent. It can inhibit cell division.

Methotrexate disodium is an tetrahydrofolate dehydrogenase inhibitor

Monomethyl auristatin E (MMAE) (MMAE), an antimitotic agent, inhibits cell division by blocking the polymerization of tubulin and also has inhibition of antibody-drug conjugates (ADCs) activity.

Thailanstatin A is an ultra-potent inhibitor of eukaryotic RNA splicing (IC50 = 650 nM). It inhibits multiple cancer cell lines via non-covalent binding to the SF3b subunit of the U2 snRNA subcomplex of the spliceosome, displaying low-nM to sub-nM IC50s. Thailanstatin A, as a payload for ADCs, is conjugated to the lysines on trastuzumab, yielding linker-less ADC.

PNU-159682, a metabolite of anthracycline neomycin, is a DNA topoisomerase II inhibitor with excellent cytotoxicity.

alpha-Amanitin (alpha-Amanitin) is the lethal toxin in Trichoderma viride and acts in vivo via the enterohepatic circulation and transport system. alpha-Amanitin induces cell death and can be used in the synthesis of ADCs. alpha-Amanitin has been shown to induce cell death and can be used in the synthesis of ADCs.

Eribulin (B1939) is a nonpaclitaxel microtubule kinetic inhibitor with anticancer activity that inhibits polymerization of microtubule protein subunits by preventing lengthening and shortening of microtubules during cell division.Eribulin is used in the study of metastatic breast cancer and solid tumors.

N-Acetyl-Calicheamicin (N-Acetyl-γ-calicheamicin) is an antibiotic with high anti-tumor activity.

Ansamitocin p-3 (Maytansinol isobutyrate) is an inhibitor of microtubule with IC50 of 3.4 μM for tubulin polymerization.

MMAF-OMe (Monomethyl auristatin F methyl ester) is an antitubulin agent which 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. MMAF-Ome is also an ADC cytotoxin.

Fluticasone propionate (CCI-187881), derived from fluticasone used to remedy asthma and allergic rhinitis, is a high affinity, selective GR (glucocorticoid receptor) agonist.

7-Epi 10-desacetyl paclitaxel (10-Deacetyl-7-epipaclitaxel) shows IC50 values of 0.085 nM, against HeLa cells.

Exatecan Mesylate (DX8951f) is a DNA topoisomerase I inhibitor (IC50: 2.2 μM, 0.975 μg/mL).

Taltobulin (HTI-286) is a synthetic analog of the tripeptide cysteine, a microtubule protein inhibitor that inhibits liver tumor cell proliferation in vitro and tumor growth in vivo.Taltobulin is cytotoxic, induces mitotic arrest and apoptosis, and may be used in the study of breast cancer and microtubule tissue-related diseases.

Budesonide (Pulmicort), an anti-inflammatory corticosteroid, has shown the effective glucocorticoid activitie and few mineralocorticoid activities. According to reports, Budesonide has extensively inhibitory effects against multiple cells types and mediators referred to allergic and nonallergic-mediated inflammatory. What's more, the anti-inflammatory action of budesonide has been revealed to contribute to the effectiveness of asthma.

1. 7-Ethylcamptothecin has the superior antitumor activity than CPT. (a). 7-Ethylcamptothecin has a stronger growth-inhibiting activity against tumor cells. (b). 7-Ethylcamptothecin remains in the intestinal tract for a longer time and in higher amounts when administered in vivo.

Dexamethasone acetate (NSC 39471) is the acetate salt form of Dexamethasone, a synthetic adrenal corticosteroid with potent anti-inflammatory properties. In addition to binding to specific nuclear steroid receptors, dexamethasone also interferes with NF-kB activation and apoptotic pathways. This agent lacks the salt-retaining properties of other related adrenal hormones.

Auristatin E, a cytotoxic tubulin modifier, disrupts cell division by inhibiting tubulin polymerisation. This compound demonstrates potent and selective antitumor activities, serving as an MMAE analog and cytotoxin in antibody-drug conjugates.

Auristatin F is an effective inhibitor of microtubule and vascular damaging agent. Auristatin F can be used in antibody-drug conjugates.

Maytansinol (Ansamitocin P-0) inhibits microtubule assembly and causes microtubule disassembly in vitro.

10-Deacetyl-7-xylosyl paclitaxel (7-Xylosyl-10-deacetyltaxol) is a Paclitaxel derivative with improved pharmacological features and higher water solubility,used in Chinese clinics to treat cancer.

DM1-SMe (DM1-SSMe) is a potent inhibitor of maytansinoid microtubular. DM1-SMe is about 3 to 10-fold more potent than the parent drug Maytansine, with IC50s of 0.003 to 0.01 nM for DM1-SMe in a panel of human tumor cell lines.

Taltobulin trifluoroacetate is a synthetic analogue of the tripeptide hemiasterlin, is a potent agent of antimicrotubule that circumvents P-glycoprotein-mediated resistance in vitro and in vivo.

(4-NH2)-Exatecan is a topoisomerase inhibitor with potential anticancer activity for the synthesis of antibody drug conjugates (ADCs).

Glucocorticoid receptor agonist-1, a potent glucocorticoid receptor agonist, has an IC50 of 2.8 nM[1].

Aldoxorubicin has effective antitumor activities in various cancer cell lines and in murine tumor models. Aldoxorubicin is an albumin-binding prodrug of Doxorubicin (DNA topoisomerase II inhibitors).

Doxorubicin (Adriamycin) is a Topoisomerase II (Top2) inhibitor with antineoplastic activity.

10-Methoxycamptothecin, a natural bioactive derivative of camptothecin (CPT) isolated from *Camptotheca acuminata*, exhibits potent anti-cancer properties.

MMAD (Demethyldolastatin 10) is a potent tubulin inhibitor. MMAD is a toxin payload in antibody drug conjugates (ADCs).

Nucleoside Derivatives - Fluoro-modified nucleosides; 5-Modified pyrimidine nucleosides; 3’-Deoxy nucleosides

Compound I, NH2-bicyclo[1.1.1]pentane-7-MAD-MDCPT hydrochloride, is a topoisomerase I inhibitor that demonstrates effective antibody-drug conjugate (ADC) activity both in vivo and in vitro, with delivery to cells facilitated through targeted antibody conjugation [1].

Fmoc-MMAF-OMe is a tubulin polymerization inhibitor and anticancer agent featuring an Fmoc protecting group. Its active component, MMAF, serves as the cytotoxic (ADC Cytotoxin) element in conventional antibody-drug conjugates (ADCs) [1].

Tubulysin E is a natural product isolated from the myxobacterial species Archangium geophyra and Angiococcus disciformis, and is a highly cytotoxic peptide.

Benzyl DC-81 (Compound 6a), an anticancer agent, exhibits antiproliferative activity against A375 and MCF-7 cells [1].