Name: SPP
Brand: BOC Sciences
Rating: 5 (1 reviews)

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Synonyms

N-succinimidyl 4-(2-pyridyldithio)pentanoate; (2,5-dioxopyrrolidin-1-yl) 4-(pyridin-2-yldisulfanyl)pentanoate

IUPAC Name

Canonical SMILES

CC(CCC(=O)ON1C(=O)CCC1=O)SSC2=CC=CC=N2

InChI

InChI=1S/C14H16N2O4S2/c1-10(21-22-11-4-2-3-9-15-11)5-8-14(19)20-16-12(17)6-7-13(16)18/h2-4,9-10H,5-8H2,1H3

InChIKey

GTBCXYYVWHFQRS-UHFFFAOYSA-N

PSA

127.17000

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In Vivo

In breast carcinoma SKBr3 cells, no SPP linker cleavage was observed, as detected by fluorescence dequenching upon internalization. By contrast, the conjugate did display fluorescence dequenching when diverted to the lysosomal pathway by geldanamycin, an effect partly due to proteolytic degradation rather than disulfide reduction. To understand why linker reduction was inefficient, redox potentials of endocytic compartments by expressing a redox-sensitive variant of GFP fused to various endocytic proteins was measured. Unexpectedly, it was found that recycling endosomes, late endosomes, and lysosomes are not reducing, but oxidizing and comparable with conditions in the endoplasmic reticulum.

NCT Number	Condition Or Disease	Phase	Start Date	Sponsor	Status
NCT00184080	Non-Hodgkin's Lymphoma	Phase 2	2014-05-21	University of Southern California	Completed
NCT00299806	Hypertension	Phase 3	2016-11-18	Novartis	Completed
NCT00376636	Hypertension	Phase 2	2007-10-30	Speedel Pharma Ltd.	Completed
NCT00344110	Hypertension	Phase 3	2016-11-18	Novartis	Completed
NCT00299832	Hypertension	Phase 3	2016-11-18	Novartis	Completed

1.Metabolites of antibody-maytansinoid conjugates: characteristics and in vitro potencies

Widdison W, Wilhelm S, Veale K, Costoplus J, Jones G, Audette C, Leece B, Bartle L, Kovtun Y, Chari R

Several antibody-maytansinoid conjugates (AMCs) are in clinical trials for the treatment of various cancers. Each of these conjugates can be metabolized by tumor cells to give cytotoxic maytansinoid metabolites that can kill targeted cells. In preclinical studies in mice, the cytotoxic metabolites initially formed in vivo are further processed in the mouse liver to give several oxidized metabolic species. In this work, the primary AMC metabolites were synthesized and incubated with human liver microsomes (HLMs) to determine if human liver would likely give the same metabolites as those formed in mouse liver. The results of these HLM metabolism studies as well as the subsequent syntheses of the resulting HLM oxidation products are presented. Syntheses of the minor impurities formed during the conjugation of AMCs were also conducted to determine their cytotoxicities and to establish how these impurities would be metabolized by HLM.