Synthesis and Biological Evaluation of Theranostic Trastuzumab–SN38 Conjugate for Near-IR Fluorescence Imaging and Targeted Therapy of HER2 Breast Cancer

Synthesis and biological evaluation of novel quaternary ammonium antibody drug conjugates based on camptothecin derivatives

“…SN38 is the active metabolite of irinotecan and DXd is the active metabolite of DS-8201a, both of which are promising candidates for ADC effector molecules [17][18][19][20][21]. Among these reported ADCs, linkers such as ester bond, carbonate [22], carbamate [23], β-glucuronide [24], AcLys-ValCit-PABC [25], Val-Ala-PABC [26], Ala-Ala-Ala [9], and GGFG [27] are usually used to link to effector molecules with primary, secondary amines or hydroxyl groups, and no relevant ADCs have been reported for highly cytotoxic camptothecin derivatives without connecting sites. Pillow et al reported a quaternary ammonium ADC based on tubulysin, a linker that ensured stable connection and traceless release of tertiary amines and exhibited excellent antitumor activity in vitro and in vivo [28].…”

Shifting the Antibody–Drug Conjugate Paradigm: A Trastuzumab-Gold-Based Conjugate Demonstrates High Efficacy against Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Mouse Model

“…Human cells that do not overexpress HER2, such as triplenegative breast cancer (MDA-MB-231) and noncancerous breast cells (MCF-10A), were chosen to assess selectivity. 29,58 We also include the cell viability for carboxylic acid precursors (1a, CREF and 1b, FIN) and auranofin (which contains the [Au(PEt 3 )] fragment present in Thio-2b and is being evaluated in different cancer clinical trials). 40,41 We routinely use auranofin in our cell viability studies of compounds that contain gold.…”

“…These doses were selected based on MTD studies with an anti-HER2 antibody and anti-HER2-based ADCs 66 as well as doses for MTD studies for auranofin and other gold(I)phosphane compounds 67 when dosed daily or every other day. Since our study was designed to assess the toxicity of ADCs which are typically dosed weekly, 58,68,69 these treatment doses and regimen were selected. Mice were intravenously injected with each dose of the drug once a week for 4 weeks.…”

Effective synthesis, development and application of a highly fluorescent cyanine dye for antibody conjugation and microscopy imaging

“…29 In spite of the fact that the relevance of cyanine conjugated antibodies is obviously high, recently, only a few examples have been published (Table S1 †). [30][31][32][33][34][35] In this regard, and as a continuation of our interest in the design and synthesis of novel asymmetric dyes [36][37][38][39][40][41][42] and antibody modification, we herein describe the development of a novel fluorescent cyanine dye. 37,43,44 The strengths of our novel asymmetric cyanine are as follows: first, we increased solubility by introducing a positively charged ionic core; second, we improved its photophysical properties, in particular increasing the Stokes shift by 25 nm, which improved image quality and reduced self-absorption, achieving an excitation maximum at the desirable 633 nm wavelength, and an improving photostability; and third, we added an azide-containing linker that enables its application in azide-alkyne click reactions, which results in an optimal fluorophore-antibody ratio.…”