Last update 01 Nov 2024

Aurora C

Last update 01 Nov 2024

Basic Info

Synonyms

AIE2, AIK3, AIRK3

+ [14]

Introduction

Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Also plays a role in meiosis and more particularly in spermatogenesis. Has redundant cellular functions with AURKB and can rescue an AURKB knockdown. Like AURKB, AURKC phosphorylates histone H3 at 'Ser-10' and 'Ser-28'. AURKC phosphorylates the CPC complex subunits BIRC5/survivin and INCENP leading to increased AURKC activity. Phosphorylates TACC1, another protein involved in cell division, at 'Ser-228'.

Drugs associated with Aurora C

NMI-900

Target

Aurora B x Aurora C

Mechanism

Aurora B inhibitors [+1]

Active Org.

GSK Plc

Originator Org.

GSK Plc

Active Indication

Neoplasms

Inactive Indication

Acute Myeloid Leukemia [+6]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Danusertib

Target

Aurora A x Aurora B x Aurora C x Bcr-Abl T315I

Mechanism

Aurora A inhibitors [+3]

Active Org.

Nerviano Medical Sciences S.r.l

Originator Org.

Nerviano Medical Sciences S.r.l

Active Indication

Philadelphia chromosome positive chronic myelogenous leukemia

Inactive Indication

Castration-Resistant Prostatic Cancer [+4]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Tozasertib

Target

Aurora A x Aurora B x Aurora C x Bcr-Abl T315I x FLT3

Mechanism

Aurora A inhibitors [+4]

Active Org.-

Originator Org.

Vertex Pharmaceuticals, Inc.

Active Indication-

Inactive Indication

Acute Lymphoblastic Leukemia [+11]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with Aurora C

EUCTR2012-005157-23-IT / Not yet recruitingPhase 1/2

A Phase I/II Study of Danusertib in Combination with Romidepsin in Adult Patients with Mature Peripheral T Cell Lymphoma (PTCL)

Start Date21 May 2013

Sponsor / Collaborator-

NCT01118611 / CompletedPhase 1IIT

A Cancer Research UK Phase I Trial to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Aurora B Inhibitor GSK1070916A in Patients With Advanced Solid Tumors

RATIONALE: Aurora B/C kinase inhibitor GSK1070916A (GSK1070916A) may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of GSK1070916A in treating patients with advanced solid tumors.

Start Date01 Mar 2010

Sponsor / Collaborator

Cancer Research UK

NCT00858377 / CompletedPhase 1

A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered AMG 900 in Adult Subjects With Advanced Solid Tumors

This first-in-human study of AMG 900 will be conducted in two parts: dose escalation and dose expansion. The dose escalation part of the study is aimed at evaluating the safety, tolerability and PK of oral AMG 900 in subjects with advanced solid tumors. Up to 50 subjects may be enrolled in dose escalation. The dose expansion part of the study will consist of 42 subjects in three taxane-resistant tumor types. The dose of AMG 900 will be dependent upon data from the dose escalation part of the study

Start Date10 Aug 2009

Sponsor / Collaborator

Amgen, Inc.

100 Clinical Results associated with Aurora C

100 Translational Medicine associated with Aurora C

0 Patents (Medical) associated with Aurora C

263

Literatures (Medical) associated with Aurora C

01 Dec 2024·Mammalian Genome

Comprehensive analysis of chromosomal breakpoints and candidate genes associated with male infertility: insights from cytogenetic studies and expression analyses

Article

Author: Kakavand, Kianoush ; Sabbaghian, Marjan ; Hassanzadeh, Vahideh ; Masoudi, Najmeh Sadat ; Meybodi, Anahita Mohseni ; Moradi, Shabnam Zarei ; Shahhoseini, Maryam ; Zamanian, Mohammadreza ; Hossein Garakani, Melika ; Ghaheri, Azadeh

The study aimed to investigate prevalent chromosomal breakpoints identified in balanced structural chromosomal anomalies and to pinpoint potential candidate genes linked with male infertility. This was acchieved through a comprehensive approach combining RNA-seq and microarray data analysis, enabling precise identification of candidate genes. The Cytogenetics data from 2,500 infertile males referred to Royan Research Institute between 2009 and 2022 were analyzed, with 391 cases meeting the inclusion criteria of balanced chromosomal rearrangement. Of these, 193 cases exhibited normal variations and were excluded from the analysis. By examining the breakpoints, potential candidate genes were suggested. Among the remaining 198 cases, reciprocal translocations were the most frequent anomaly (129 cases), followed by Robertsonian translocations (43 cases), inversions (34 cases), and insertions (3 cases).Some patients had more than one chromosomal abnormality. Chromosomal anomalies were most frequently observed in chromosomes 13 (21.1%), 14 (20.1%), and 1 (16.3%) with 13q12, 14q12, and 1p36.3 being the most prevalent breakpoints, respectively. Chromosome 1 contributed the most to reciprocal translocations (20.2%) and inversions (17.6%), while chromosome 14 was the most involved in the Robertsonian translocations (82.2%). The findings suggested that breakpoints at 1p36.3 and 14q12 might be associated with pregestational infertility, whereas breakpoints at 13q12 could be linked to both gestational and pregestational infertility. Several candidate genes located on common breakpoints were proposed as potentially involved in male infertility. Bioinformatics analyses utilizing three databases were conducted to examine the expression patterns of 78 candidate genes implicated in various causes of infertility.‏ In azoospermic individuals, significant differential expression was observed in 19 genes: 15 were downregulated (TSSK2, SPINK2, TSSK4, CDY1, CFAP70, BPY2, BTG4, FKBP6, PPP2R1B, SPECC1L, CENPJ, ‏SKA3, FGF9, NODAL, CLOCK), while four genes were upregulated ‏(‏HSPB1, MIF, PRF1, ENTPD6). In the case of Asthenozoospermia, seven genes showed significant upregulation (PRF1, DDX21, KIT, SRD5A3, MTCH1, DDX50, NODAL). Though RNA-seq data for Teratozoospermia were unavailable, microarray data revealed differential expression insix genes: three downregulated (BUB1, KLK4, PIWIL2) and three upregulated (AURKC, NPM2, RANBP2). These findings enhance our understanding of the molecular basis of male infertility and could provide valuable insights for future diagnostic and therapeutic strategies.

01 Sep 2024·Acta Crystallographica Section D Structural Biology

Surface-mutagenesis strategies to enable structural biology crystallization platforms

Article

Author: Hilpmann, André ; Egner, Ursula ; Hillig, Roman Christian ; Pütter, Vera ; Holton, Simon James ; Schaefer, Martina

A key prerequisite for the successful application of protein crystallography in drug discovery is to establish a robust crystallization system for a new drug-target protein fast enough to deliver crystal structures when the first inhibitors have been identified in the hit-finding campaign or, at the latest, in the subsequent hit-to-lead process. The first crucial step towards generating well folded proteins with a high likelihood of crystallizing is the identification of suitable truncation variants of the target protein. In some cases an optimal length variant alone is not sufficient to support crystallization and additional surface mutations need to be introduced to obtain suitable crystals. In this contribution, four case studies are presented in which rationally designed surface modifications were key to establishing crystallization conditions for the target proteins (the protein kinases Aurora-C, IRAK4 and BUB1, and the KRAS–SOS1 complex). The design process which led to well diffracting crystals is described and the crystal packing is analysed to understand retrospectively how the specific surface mutations promoted successful crystallization. The presented design approaches are routinely used in our team to support the establishment of robust crystallization systems which enable structure-guided inhibitor optimization for hit-to-lead and lead-optimization projects in pharmaceutical research.

01 Aug 2024·iScience

Spatio-temporal requirements of Aurora kinase A in mouse oocyte meiotic spindle building

Article

Author: Drutovic, David ; Blengini, Cecilia S ; Schindler, Karen ; Schier, Jan ; Vaskovicova, Michaela

Meiotic spindles are critical to ensure chromosome segregation during gamete formation. Oocytes lack centrosomes and use alternative microtubule-nucleation mechanisms for spindle building. How these mechanisms are regulated is still unknown. Aurora kinase A (AURKA) is essential for mouse oocyte meiosis because in pro-metaphase I it triggers microtubule organizing-center fragmentation and its expression compensates for the loss of the two other Aurora kinases (AURKB/AURKC). Although knockout mouse models were useful for foundational studies, AURK spatial and temporal functions are not yet resolved. We provide high-resolution analyses of AURKA/AURKC requirements during meiotic spindle-building and identify the subcellular populations that carry out these functions: 1) AURKA is required in early spindle assembly and later for spindle stability, whereas 2) AURKC is required in late pro-metaphase, and 3) Targeted AURKA constructs expressed in triple AURK knockout oocytes reveal that spindle pole-localized AURKA is the most important population controlling spindle building and stability mechanisms.

News (Medical) associated with Aurora C

15 Mar 2023

·www.prnewswire.com

Jacobio Pharma to Present Data of Three Preclinical Studies at the 2023 AACR Annual Meeting

BEIJING and SHANGHAI and BOSTON, Mass., March 14, 2023 /PRNewswire/ -- Jacobin Pharma (1167.HK) today announced that the company will present the results of three preclinical studies of KRASmulti inhibitor JAB-23425, CD73-STING iADC JAB-X1800, and Aurora kinase A inhibitor JAB-2485 in form of the abstract during the American Association for Cancer Research (AACR) Annual Meeting 2023 (the "AACR 2023") from April 14 to 19, 2023. Details for the 2023 AACR abstracts are as follows: Abstract Number:1660 Abstract Title : Preclinical investigation of orally bioavailable, potent KRASMulti inhibitor JAB-23425 Session: Novel Antitumor Agents 4 Time: April 17, 2023, 9:00 AM – 12:30 PM (ET) KRASmulti inhibitor JAB-23425 targets multiple KRAS mutants in both RAS(ON) and RAS (OFF), with good selectivity over HRAS and NRAS. JAB-23425 has significant antitumor effect on cancer models with multiple KRAS mutations (such as G12D, G12V, and G13D) and amplification of wild type KRAS, and has no inhibitory effect on KRAS-independent cells. The KRASmulti inhibitor JAB-23425 is expected to solve the unmet clinical needs of patients with KRAS-mutated tumors. JAB-23425 is a leading compound of Jacobio's KRASmulti inhibitor. Abstract Number: 2923 Abstract Title : JAB-X1800: a potent immunostimulatory antibody-drug conjugate (iADC) targeting CD73 Session: Therapeutic Antibodies 2 Time: April 17, 2023, 1:30 PM – 5:00 PM (ET) JAB-X1800 is the world's first iADC by conjugating Jacobio's STING agonist to CD73 antibody, which is expected to turn the tumor from "cold" to "hot," and combine synergize with anti-PD-1 mAb. Abstract Number: 1645 Abstract Title: JAB-2485: a potent, highly selective small-molecule Aurora kinase A inhibitor that targets cell division Session : Novel Antitumor Agents 4 Time: April 17, 2023, 9:00 AM – 12:30 PM (ET) JAB-2485 is one of the top two highly selective Aurora A inhibitors with 1500-fold selectivity over Aurora kinase B and Aurora kinase C, with high activity and low bone marrow toxicity as well as favorable PK properties. "Jacobio leverages our IADDP (Induced Allosteric Drug Discovery Platform) to develop drugs aiming specific undruggable targets," said Dr. WANG Yinxiang, chairman and CEO of Jacobio, "These preclinical data are part of the research and development achievements of Jacobio since its establishment 8 years ago, and we will continue to transform the fundamental research in academia into clinical achievements through independent R&D in the future." The 2023 AACR Annual Meeting will be held in Orlando, Florida, USA from April 14th to April 19th. For more information, please visit the official website of the AACR: About Jacobio Jacobio(1167.HK) is committed to providing more products and solutions to people's health. Our mission is to provide compelling innovations for creating a pipeline of life-changing medicines. Our vision is to become a global leader recognized for our impact in drug R&D together with our partners. The company's R&D centers are located in Beijing, Shanghai and MA, with a platform and expertise in developing allosteric inhibitors against protein tyrosine phosphatase, KRAS and transcriptional factors. SOURCE Jacobio Pharma

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Aurora C

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