PM534, a Novel Colchicine Site Tubulin Inhibitor with Broad-Spectrum and Resistance-Overcoming Antitumor Activity

Sep 22, 2026

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PM534 is evaluated as a novel colchicine-binding domain tubulin inhibitor for anticancer therapy. In vitro testing on 14 human cancer cell lines, including breast, ovarian, and prostate cancers, shows strong potency, with half-growth effects in the low-nanomolar range. Continuous and short exposure drives irreversible G2–M arrest, multinucleation, impaired angiogenesis, and reduced HUVEC functions. In multiple xenograft models, PM534 increases median survival without systemic toxicity, induces apoptosis/mitotic catastrophe/necrosis, and retains activity against multidrug-resistant P-glycoprotein or β-III tubulin overexpression. A phase I trial is ongoing.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Introduction

Tubulin regulation and druggable sites

Microtubule-destabilizing vs microtubule-stabilizing agents

PM534, a Novel Colchicine Site Tubulin Inhibitor with Broad-Spectrum and Resistance-Overcoming Antitumor Activity Pablo Aviles1, Marcelo Lima Ribeiro1, Maria Jose Guilln1, Marta Martinez-Diez1, Maria Jose Muñoz-Alonso1, Gema Santamaria-Nuñez1, Daniel Torralba1, Patricia Alamo2,3, Alberto Gallardo4, Mara A. Oliva5, Ramon Mangues2,3, J. Fernando Diaz5, and Carmen Cuevas1 | | | A | | B | S | | T | R | | A | | C | T | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | This study evaluates PM534, a novel colchicine-binding domain inhibitor, for its potential in cancer therapy. PM534 exhibited potent in vitro efficacy against a panel of 14 human cancer cell lines, including breast, ovarian, and prostate cancers, with concentration needed to reduce the growth of treated cells to half that of untreated cells values in the low nanomolar range. Both continuous (72 hours) and short-term (1–24 hours) exposure led to irreversible effects, inducing G2–M cell cycle arrest and multinucleation. Additionally, PM534 also impaired angiogenic process. It effectively inhibited HUVEC functions, including adhesion, with an IC50 of 2.3 nmol/L, markedly more potent than colchicine (IC50 ¼ 1,800 nmol/L) . At concentrations as low as 1.6 nmol/L, PM534 delayed wound closure in migration assays, completely inhibiting migration above 4 nmol/L. Additionally, PM534 abrogated invasion and disrupted capillary-like network formation at concentrations starting from 0.5 nmol/L without
􀀶 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | inducing cytotoxicity. In vivo PM534 demonstrated robust antitumor efficacy across six xenograft models, including ovarian (A2780 and ES-2), triple-negative breast (MDA-MB-231 and HCC1937), and prostate (VCaP and 22Rv1) tumors. This treatment also led to statistically significant increases in median survival times across all models, without inducing signs of systemic toxicity. Mechanistically, PM534 induced apoptosis, mitotic catastrophe, and necrosis in tumor tissues. Importantly, PM534 retained efficacy in models overexpressing multidrug resistance proteins P-glycoprotein or β-III tubulin, overcoming common resistance mechanisms that limit the effectiveness of other tubulinbinding agents. Collectively, these findings highlight PM534 as a promising antitumor agent with potent activity against diverse and treatment-resistant malignancies. A phase I clinical trial (NCT\#5835609) is underway to assess the therapeutic potential of PM534 in patients with advanced solid tumors. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Introduction Tubulin is a GTP-regulated protein that plays a central role in the formation of microtubules. When bound to GTP, tubulin is in its active form, allowing it to self-assemble into microtubules. After the microtubules are formed, tubulin’s intrinsic GTPase activity is activated, converting GTP into GDP. The GDP-bound form of tubulinis inactive, which leads to the disassembly of microtubules. Curre

FAQs

What is PM534 and which tubulin target does it inhibit?

PM534 is a novel colchicine-binding domain inhibitor targeting tubulin regulatory interactions involved in microtubule dynamics.

How does PM534 affect cancer cell behavior in vitro?

PM534 shows potent growth inhibition across a panel of cancer cell lines and induces irreversible G2–M cell cycle arrest and multinucleation. It also impairs angiogenesis-related functions in endothelial cells.

Does PM534 work in vivo and how does it relate to drug resistance?

PM534 demonstrates robust antitumor efficacy across multiple xenograft models with increased median survival and no signs of systemic toxicity. It retains efficacy in models overexpressing multidrug resistance proteins P-glycoprotein or β-III tubulin, overcoming common resistance mechanisms.

Sep 22, 2026

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