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Last update 08 May 2025

TACC3

Last update 08 May 2025

Basic Info

Synonyms

ERIC-1, ERIC1, maskin

+ [4]

Introduction

Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors (By similarity). Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:21297582, PubMed:23532825). May be involved in the control of cell growth and differentiation. May contribute to cancer (PubMed:14767476).

Drugs associated with TACC3

AO-252

Target

TACC3

Mechanism

TACC3 inhibitors

Active Org.

A2a Pharmaceuticals, Inc.

[+1]

Originator Org.

OncoCube Therapeutics LLC [+1]

Active Indication

Endometrial Carcinoma [+5]

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SNIPER(TACC3)-16

Target

FGFR3 x TACC3

Mechanism

FGFR3 antagonists [+1]

Active Org.

National Institute of Health Sciences

Originator Org.

National Institute of Health Sciences

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

KHS-101

Target

TACC3

Mechanism

TACC3 inhibitors

Active Org.

The Scripps Research Institute [+2]

Originator Org.

The Scripps Research Institute

Active Indication

Glioblastoma [+3]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with TACC3

NCT06136884

/ RecruitingPhase 1

A First-In-Human, Phase 1 Study Evaluating Oral TACC3 PPI Inhibitor, AO-252, in Advanced Solid Tumors

The purpose of this study is to assess the safety, tolerability and efficacy of the study drug AO-252 and identify the best dose for use in future studies.

Start Date02 Nov 2023

Sponsor / Collaborator

A2a Pharmaceuticals, Inc.

100 Clinical Results associated with TACC3

100 Translational Medicine associated with TACC3

0 Patents (Medical) associated with TACC3

433

Literatures (Medical) associated with TACC3

02 Jun 2025·Journal of Cell Biology

Structural characterization and inhibition of the interaction between ch-TOG and TACC3

Article

Author: Royle, Stephen J. ; Rostkova, Elena ; Bayliss, Richard ; Tomlinson, Darren C. ; Larocque, Gabrielle ; Fielding, Alistair J. ; Pfuhl, Mark ; Burgess, Selena G. ; Richards, Mark W. ; Shelford, James ; Tiede, Christian ; Daviter, Tina ; Sampson, Josephina ; Calabrese, Antonio N.

The mitotic spindle is a bipolar array of microtubules, radiating from the poles which each contain a centrosome, embedded in pericentriolar material. Two proteins, ch-TOG and TACC3, have multiple functions at the mitotic spindle due to operating either alone, together, or in complex with other proteins. To distinguish these activities, we need new molecular tools to dissect their function. Here, we present the structure of the α-helical bundle domain of ch-TOG that mediates its interaction with TACC3 and a structural model describing the interaction, supported by biophysical and biochemical data. We have isolated Affimer tools to precisely target the ch-TOG-binding site on TACC3 in live cells, which displace ch-TOG without affecting the spindle localization of other protein complex components. Inhibition of the TACC3–ch-TOG interaction led unexpectedly to fragmentation of the pericentriolar material in metaphase cells and delayed mitotic progression, uncovering a novel role of TACC3–ch-TOG in maintaining pericentriolar material integrity during mitosis to ensure timely cell division.

01 Mar 2025·Virchows Archiv

FGFR3::TACC3 fusions in head and neck carcinomas: a study of nine cases highlighting phenotypic heterogeneity, frequent HPV association, and a morphologically distinct subset in favor of a putative entity

Article

Author: Bell, Diana ; Antonescu, Cristina R ; Agaimy, Abbas ; Laco, Jan ; Dermawan, Josephine K ; Kester, Lennart A ; Breimer, Gerben E ; Bishop, Justin A ; Stoehr, Robert ; Rijken, Johannes A ; Cramer, Thomas ; Whaley, Rumeal D

AbstractThe FGFR3::TACC3 fusion has been reported in subsets of diverse cancers including urothelial and squamous cell carcinomas (SCC). However, the morphology of FGFR3::TACC3-positive head and neck carcinomas has not been well studied and it is unclear if this fusion represents a random event, or if it might characterize a morphologically distinct tumor type. We describe nine FGFR3::TACC3 fusion–positive head and neck carcinomas affecting six males and three females aged 38 to 89 years (median, 59). The tumors originated in the sinonasal tract (n = 4), parotid gland (n = 2), and one case each in the oropharynx, submandibular gland, and larynx. At last follow-up (9–21 months; median, 11), four patients developed local recurrence and/or distant metastases, two died of disease at 11 and 12 months, one died of other cause, one was alive with disease, and two were disease-free. Three of six tumors harbored high risk oncogenic HPV infection (HPV33, HPV18, one unspecified). Histologically, three tumors revealed non-keratinizing transitional cell-like or non-descript morphology with variable mixed inflammatory infiltrate reminiscent of mucoepidermoid or DEK::AFF2 carcinoma (all were HPV-negative), and three were HPV-associated (all sinonasal) with multiphenotypic (1) and non-intestinal adenocarcinoma (2) pattern, respectively. One salivary gland tumor showed poorly cohesive large epithelioid cells with prominent background inflammation and expressed AR and GATA3, in line with a possible salivary duct carcinoma variant. Two tumors were conventional SCC. Targeted RNA sequencing revealed an in-frame FGFR3::TACC3 fusion in all cases. This series highlights heterogeneity of head and neck carcinomas harboring FGFR3::TACC3 fusions, which segregates into three categories: (1) unclassified HPV-negative category, morphologically distinct from SCC and other entities; (2) heterogeneous group of HPV-associated carcinomas; and (3) conventional SCC. A driver role of the FGFR3::TACC3 fusion in the first category (as a potential distinct entity) remains to be further studied. In the light of available FGFR-targeting therapies, delineation of these tumors and enhanced recognition is recommended.

01 Mar 2025·Bioorganic Chemistry

Isoxazole-pyrimidine derivatives as TACC3 inhibitors: A novel modality to targeted cancer therapy

Article

Author: Banoglu, Erden ; Saatci, Özge ; Çalışkan, Kübra ; Lengerli, Deniz ; Şahin, Özgür ; Çalışkan, Burcu ; Çalışkan, Özge Akbulut ; Vempati, Sridhar ; Lim, Chaemin

Inhibiting the function of transforming acidic coiled-coil 3 (TACC3) offers a promising therapeutic approach for various cancers, such as breast, ovarian, and lung cancers.Our previous work introduced BO-264 as a novel chemotype for inhibiting TACC3 function, though it exhibited relatively low metabolic stability. In this study, sixty-two compounds were designed and synthesized to modify the structure of BO-264 to improve its metabolic stability while maintaining its potency. The tractable SAR results obtained by these novel analogs indicated that appropriate substitutions on the left-end phenyl-isoxazole and right-end morpholine groups improved metabolic stability while preserving potency. Among these, compound 13b exhibited approximately sevenfold improvement in metabolic stability and bioavailability while maintaining strong potency and a favorable safety profile. 13b markedly increased the levels of p-Histone H3 (Ser10), cleaved PARP, and p-H2AX (Ser139), indicative of mitotic arrest, apoptosis, and DNA damage, respectively. In addition, the protein-drug binding assay, DARTS, identified TACC3 as a biologically significant target of 13b, positioning it as an advanced lead compound for further development of clinically relevant TACC3 inhibitors in cancers with elevated TACC3 expression.

News (Medical) associated with TACC3

11 Dec 2024

·www.prnewswire.com

A2A Pharmaceuticals, Inc. Announces Phase 1 Clinical Trial Advancements in TACC3 Inhibition Program Targeting Multiple Cancers

NEW YORK, Dec. 11, 2024 /PRNewswire/ -- A2A Pharmaceuticals, Inc. ("A2A or "the company"), a clinical-stage pioneering biopharmaceutical company focused on developing innovative cancer therapies, today announced significant progress in its clinical studies exploring TACC3 (Transforming Acidic Coiled-Coil 3) inhibition in patients with ovarian cancer, triple-negative breast cancer (TNBC), and endometrial cancer, as well as other malignancies. A2A Pharmaceuticals has progressed into cohort 4, an important inflection point in its Phase 1 clinical trial to assess the safety and efficacy of its lead TACC3 inhibitor, A0-252. Early results have shown strong safety and efficacy profiles with the potential for a wide therapeutic index in these patient populations. "We are excited about the advancements in our TACC3 program and its potential for patients with challenging cancer diagnoses. The company is continually exploring collaborations and partnerships to accelerate development timelines and enhance patient access to cutting-edge treatments," said Sotirios Stergiopoulos, M.D. President, CEO and Founder, A2A Pharmaceuticals, Inc. "Our focus on understanding the biology of cancer and leveraging innovative targeted therapies underscores our commitment to transforming cancer care and improving outcomes for patients." "While our current focus with AO-252 is on addressing the unmet needs in ovarian, TNBC, and endometrial cancers, we are equally excited about its potential to benefit patients in other indications in the future," said Robbin Frnka, vice president of Clinical Operations. "This is just the beginning of our journey, and we look forward to exploring broader applications of this promising treatment option to make an even greater impact across multiple indications of need." "This trial represents a promising step forward in delivering therapies that could impact the standard of care for patients," said Alex Spira, Principal Investigator of Next Oncology Virginia. "A2A Pharmaceuticals is committed to supporting the cancer community by advancing novel therapies that target the underlying biology of tumors." Key Highlights of the TACC3 Program: The selected cancers are characterized by limited treatment options and high rates of recurrence in patients. A2A's TACC3 inhibitor is designed to disrupt critical cellular mechanisms involved in cancer cell proliferation, providing a much-needed new avenue of treatment for patients battling these aggressive malignancies. Beyond these indications, pre-clinical studies suggest A2A's TACC3 PPI inhibitor may also show efficacy in other solid tumors, including gastric and prostate cancers, sarcomas and certain hematologic malignancies. Ongoing research efforts are focused on expanding the indication spectrum and optimizing treatment regimens for diverse cancer types. About A2A Pharmaceuticals, Inc. A2A Pharmaceuticals, Inc. is a biotechnology company dedicated to developing innovative therapeutics for cancer treatment. With a focus on novel targets and precision medicine approaches, A2A Pharmaceuticals strives to improve the quality of life and survival rates for cancer patients through the advancement of targeted therapies. Media Contact: Julie Ferguson Communications Consultant, JFPRMEDIAGROUP A2A Pharmaceuticals, Inc. 312-385-0098 [email protected] SOURCE A2A Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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TACC3

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