Last update 01 Nov 2024

MUC1 x Tubulin

Last update 01 Nov 2024

Basic Info

Related Targets

MUC1Tubulin

Drugs associated with MUC1 x Tubulin

SAR-566658

Target

MUC1 x Tubulin

Mechanism

MUC1 modulators [+1]

Active Org.-

Originator Org.

ImmunoGen, Inc.

Active Indication-

Inactive Indication

Breast Cancer [+2]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with MUC1 x Tubulin

NL-OMON46882 / CompletedPhase 2

Open-label Phase 2 study evaluating efficacy and safety of SAR566658 treatment in patients with CA6 positive metastatic Triple Negative Breast Cancer - ACT14884

Start Date26 Jul 2017

Sponsor / Collaborator

Sanofi-Aventis Ltd.

NCT02984683 / TerminatedPhase 2

Open-label Phase 2 Study Evaluating Efficacy and Safety of SAR566658 Treatment in Patients With CA6 Positive Metastatic Triple Negative Breast Cancer

Primary Objective:
To evaluate the tumor Objective Response Rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) of SAR566658 in participants with anti-carbonic anhydrase 6 (CA6)-positive metastatic triple negative breast cancer (TNBC). Part 1: To select the SAR566658 dose based on ORR and safety of 2 dose levels of SAR566658. Part 2: Part 2a: To demonstrate the activity of SAR566658 based on ORR in participants overexpressing CA6 (membrane intensity of 2+, 3+ in greater than or equal to (>=) 30% of tumor cells) treated at the selected dose in an expanded cohort, in addition to the participants treated in Part 1. - Part 2b: To assess the efficacy in participants with metastatic TNBC and mild CA6 expression.
Secondary Objectives:
To assess:
Disease Control Rate (DCR), Duration of Response (DOR), Progression-Free Survival (PFS), and Time To Progression (TTP).
The impact of ocular primary prophylaxis on the incidence of keratopathies.
The potential immunogenicity of SAR566658.
To evaluate the global safety profile.

Start Date23 Mar 2017

Sponsor / Collaborator

Sanofi

NCT01156870 / CompletedPhase 1

Dose Escalation, Safety and Pharmacokinetic, First in Man Study, of SAR566658 Administered as a Single Agent by Intravenous Infusion in Adult Patients With CA6-Positive and Refractory Solid Tumors

Primary Objective:
To determine the maximum tolerated dose (MTD) of SAR566658
Secondary Objectives:
To characterize the safety profile of SAR566658
To evaluate the pharmacokinetic profile of SAR566658
To assess the potential immunogenicity of SAR566658
To assess preliminary antitumor activity
To assess the effect of SAR566658 at recommended dose on CYP3A enzyme activity using midazolam
To assess safety in the alternative schedules of SAR566658 administration

Start Date08 Sep 2010

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with MUC1 x Tubulin

100 Translational Medicine associated with MUC1 x Tubulin

0 Patents (Medical) associated with MUC1 x Tubulin

Literatures (Medical) associated with MUC1 x Tubulin

01 Apr 2022·Translational Lung Cancer ResearchQ2 · MEDICINE

Picropodophyllin inhibits the growth of pemetrexed-resistant malignant pleural mesothelioma via microtubule inhibition and IGF-1R-, caspase-independent pathways

Q2 · MEDICINE

Article

Author: Sun, Rong ; Amano, Yoshihiro ; Haque, Eshat Fahmida ; Isobe, Takeshi ; Tanino, Ryosuke ; Tong, Xuexia ; Tsubata, Yukari

BackgroundAcquired pemetrexed resistance leads to treatment interruption in patients with malignant pleural mesothelioma (MPM). Insulin-like growth factor-I receptor (IGF-1R) inhibitor is a candidate for treating pemetrexed-naïve MPM. However, the efficacy of cytotoxic and targeted drugs in acquired-pemetrexed resistant MPM is unclear. We explored anticancer drugs, including the IGF-1R inhibitor picropodophyllin, against acquired pemetrexed-resistant MPMs.MethodsAcquired pemetrexed-resistant human MPM cell lines, named as H2452/PEM and 211H/PEM after their parental lines H2452 and 211H, respectively, were established by exposure to pemetrexed in vitro. Picropodophyllin and siRNA for IGF-1R knockdown were used to evaluate the efficacy of IGF-1R inhibition. Immunofluorescence was used to evaluate microtubule localization. The efficacy of picropodophyllin was evaluated in 3-dimensional MPM models.ResultsThe acquired pemetrexed-resistant MPM lines retained their resistance after the removal of culture treatment. IGF-1R levels in H2452/PEM cells were higher than those in H2452 cells but not in 211H/PEM cells compared to the respective parental line. Picropodophyllin induced sub-G1 arrest in H2452/PEM cells but induced G2/M phase arrest in 211H/PEM cells, leading to caspase-independent cell death in the two acquired pemetrexed-resistant MPM lines. Although picropodophyllin inhibited phosphorylation of IGF-1R, specific inhibition of IGF-1R by RNA interference did not reduce the viability of pemetrexed-resistant MPM lines. Additionally, picropodophyllin reduced the viability of both IGF-1R knockdown pemetrexed-resistant MPM cells. Picropodophyllin was cytotoxic in acquired-pemetrexed-resistant MPM lines because of inhibition of microtubule formation and induction of aberrant mitosis. Moreover, combination treatment with picropodophyllin and vinorelbine synergistically affected the pemetrexed-resistant MPM lines but not the parental lines. Furthermore, we observed a similar efficacy of picropodophyllin in 3-dimensional pemetrexed-resistant MPM models.ConclusionsPicropodophyllin may offer novel therapeutic properties for treating acquired pemetrexed-resistant MPM. Targeting tubulin may be an important strategy in the treatment of MPM after the discontinuation of pemetrexed.

01 Jul 2018·Molecular NeurobiologyQ2 · MEDICINE

Validation of Reference Genes for Expression Studies in Human Meningiomas under Different Experimental Settings

Q2 · MEDICINE

Article

Author: Kalff, Rolf ; Walter, Jan ; Freitag, Diana ; Koch, Arend ; Lawson McLean, Aaron

Quantitative polymerase chain reaction (qPCR) is a sensitive technique for the quantitative analysis of gene expression levels. To compare mRNA transcripts across tumour and non-pathological tissue, appropriate reference genes are required for internal standardisation. Validation of these reference genes in meningiomas has not yet been reported. After mRNA transcription of meningioma (WHO grade I-III) and meningeal tissue from three different experimental sample types (fresh tissue, primary cell cultures and FFPE tissue), 13 candidate reference genes (ACTB, B2M, HPRT, VIM, GAPDH, YWHAZ, EIF4A2, MUC1, ATP5B, GNB2L, TUBB, CYC1, RPL13A) were chosen for quantitative expression analysis. Two statistical algorithms (GeNorm and NormFinder) were used for validation of gene expression stability. All candidate housekeepers tested for stability were checked within and across the three tissue analysis groups. Pearson correlation, the ΔC _t method and ranking analysis identified the most non-regulated genes suitable for internal standardisation. TUBB, HPRT and ACTB were the most stably expressed genes for all analysis groups across meningioma and non-pathological meningeal tissue combined. In contrast, analysis of the consistency of reference gene expression within specific meningioma and meningeal tissues resulted in specific reference gene rankings for each tissue type. Future gene expression analyses require reference genes to be chosen that are suitable for the tissue types and for the experimental paradigms being studied. Validation of candidate housekeeper genes in meningiomas for quantitative real-time polymerase chain reaction revealed for the first time TUBB, ACTB and HPRT as the most consistently expressed genes among meningioma and non-pathological meningeal tissue across a range of experimental settings.

01 Jan 2017·Advanced Healthcare Materials

Synergistic Anticancer Effect of Peptide‐Docetaxel Nanoassembly Targeted to Tubulin: Toward Development of Dual Warhead Containing Nanomedicine

Article

Author: Biswas, Atanu ; Jana, Batakrishna ; Mohapatra, Saswat ; Ghosh, Surajit ; Saha, Abhijit ; Ghosh, Subhajit ; Mondal, Prasenjit

Microtubule dynamics play a crucial role in cancer cell division. Various drugs are developed to target microtubule. Although a few of them show potential in treatment of cancer, but success rate is limited due to their poor bioavailability and lack of specificity. Thus, development of highly bioavailable and target specific anticancer drug is extremely necessary. To address these key issues, here, a combination of approaches such as development of a dodecapeptide‐docetaxel nanoassembly targeted to tubulin and MUC1 (mucin 1, cell surface associated glycoprotein) targeting oligonucleotide aptamer conjugated liposome for delivering peptide‐docetaxel nanoassembly into the breast cancer cell have been demonstrated. These studies reveal that the peptide forms nanoassembly and entraps docetaxel drug. Further, the liposomal formulation of peptide‐docetaxel exerts synergistic anticancer effect, activates key mitotic check point proteins, and inhibits bipolar spindle formation, metastatic cancer cell migration, and growth of tumor mimicking 3D multicellular spheroid.

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