NMS-P528 

NMS-P528 is a DNA minor groove alkylating agent and ADC payload. NMS-P528 undergoes intramolecular cyclization to form reactive electrophilic derivatives, which in turn induce DNA damage, cell cycle arrest, and Apoptosis. NMS-P528 shows no significant anti-tumor activity as a free payload in a HER2-negative Raji lymphoma mouse xenograft model. NMS-P528 serves as the cytotoxic payload for the antibody-drug conjugate EV20/NMS-P945. NMS-P528 can be used in research related to breast cancer, gastric cancer, colon adenocarcinoma, Burkitt's lymphoma, neuroblastoma, pancreatic cancer, prostate cancer, head and neck cancer, ovarian cancer, and melanoma^[1][2][3].

NMS-P528 (gradient concentrations; 72 h) potently inhibits the proliferation of a panel of 30 distinct tumor cell lines, with a mean IC₅₀ of 0.202 nM following 72-hour treatment^[1].
NMS-P528 (gradient concentrations; 72-144 h) circumvents multi-drug resistance in A2780/ADR ovarian cancer cells, and exhibits similar antiproliferative activity against parental A2780 cells, with resistance indices of 1.2 (72 h) and 1.8 (144 h)^[1].
NMS-P528 (30 μM; up to 24 h) has a short plasma half-life in mouse, rat, and cynomolgus monkey plasma, which are 0.46, 0.22, and 0.34 h respectively, due to rapid spirocyclization and subsequent inactivation^[1].
NMS-P528 (gradient concentrations; 144 h) potently inhibits the proliferation of the tumor cell lines HCC1569, HCC1954, NCI-N87, Hs-578-T and SW620, with a mean IC₅₀ value ranging from 0.010 to 0.025 nM after 144 h of treatment^[1].
NMS-P528 (1 nM; 24-72 h) induces DNA damage, cell cycle arrest and apoptosis in HCC1954 breast cancer cells, which is evidenced by increased positive rate of p-H2AX, decreased BrdUrd incorporation and expanded sub-G₁ cell population^[1].
NMS-P528 induces apoptosis in human neuroblastoma cell lines SK-N-AS, COG-N-453, NBL-S, Felix and NB-1 at its IC₅₀ concentration, which is confirmed by an increased annexin V-positive rate^[2].
NMS-P528, delivered via EV20/NMS-P945, exerts potent, target-dependent cytotoxic activity against a variety of tumor cell lines in vitro, with stronger activity in HER-3-highly expressing cells including MDA-MB-435, Sk-mel 24, DU145, Fadu, OVCAR-8, SNU638 and WM115^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

NMS-P528 (0.5 mg/kg; i.v.; single dose) does not inhibit tumor growth in a Raji Burkitt lymphoma xenograft model in female SCID mice^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

510.05

C₂₇H₂₈ClN₃O₃S

1466546-45-1

ClC[C@@H](C1=C2C=C(O)C3=C1C(C)=CS3)CN2C(C(N4)=CC5=C4C=CC(OCCN6CCCC6)=C5)=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Valsasina B, et al. Novel Thienoduocarmycin-Trastuzumab ADC Demonstrates Strong Antitumor Efficacy with Favorable Safety Profile in Preclinical Studies. Molecular cancer therapeutics. 2023 Dec 01;22(12):1465-1478.  [Content Brief]

  [2]. Sano R, et al. An antibody-drug conjugate directed to the ALK receptor demonstrates efficacy in preclinical models of neuroblastoma. Science translational medicine. 2019 Mar 13;11(483):eaau9732.  [Content Brief]

  [3]. Capone E, et al. EV20/NMS-P945, a Novel Thienoindole Based Antibody-Drug Conjugate Targeting HER-3 for Solid Tumors. Pharmaceutics. 2021 Apr 02;13(4):483.