Nitro-PDS-Tubulysin M

Nitro-PDS-Tubulysin M 是基于季铵的生物可逆连接，用于靶向递送，可以改善药代动力学和治疗指数。MC-Sq-Cit-PAB-Dolastatin10 用于抗体-药物偶联物 (antibody-drug conjugates) 以治疗各种疾病或病症，例如肿瘤抗原的过表达。

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Background

Nitro-PDS-Tubulysin M has a bioreversible linkage based on a quaternary ammonium for targeted delivery and it can improve pharmacokinetics and the therapeutic index. Nitro-PDS-Tubulysin M is used for the antibody-drug conjugates (ADC) to treat various diseases or disorders, e.g. characterized by the overexpression of a tumor antigen[1,2].

ADC2-2 (anti-CD22 10F4v3 LC K149C Nitro-PDS-Tubulysin M) displays target-specific killing in WSU-DLCL2 human diffuse large B-cell lymphoma tumors with IC50 of 0.147 nM, and ADC2-1 (anti-Napi2b 10H1.11.4B LC K149C Nitro-PDS-Tubulysin M) displays target-specific killing in human ovarian cancer IGROV-1 and OVCAR-3x2.1 with IC50s of 2.07 nM, 1.004 nM, respectively[1].

[1]. FLYGARE, John A, et al. Quaternary amine compounds and antibody-drug conjugates thereof. WO2016090050A1. [2]. Staben LR, et al. Targeted drug delivery through the traceless release of tertiary and heteroaryl amines from antibody-drug conjugates. Nat Chem. 2016 Dec;8(12):1112-1119.