unesbulin (BMIi-1) / PTC Therap 
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 0 Diseases   3 Trials   3 Trials   54 News 


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  • ||||||||||  unesbulin (BMIi-1) / PTC Therap
    Trial primary completion date:  A Phase 1b Study of PTC596 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma and High Grade Glioma (clinicaltrials.gov) -  Jun 21, 2024   
    P1,  N=64, Active, not recruiting, 
    Unesbulin 300 mg twice per week plus DTIC 1,000 mg/m2 once every 21 days was identified as the RP2D, demonstrating a favorable benefit-risk profile in a heavily pretreated population of adults with advanced LMS. Trial primary completion date: Aug 2024 --> Mar 2024
  • ||||||||||  unesbulin (BMIi-1) / PTC Therap
    Determining the nuclear and cytoplasmic function of BMI-1 in diffuse intrinsic pontine glioma during M phase (Section 21) -  Mar 5, 2024 - Abstract #AACR2024AACR_2605;    
    We have previously shown that PTC596, a potent BMI-1 modulator, induces chromosome scattering, M phase cell-cycle arrest, BMI-1 phosphorylation and translocation to the cytoplasm leading to the inhibition of its PRC1 canonical function and cell death...We are currently investigating potential pathways involved in BMI-1 nuclear-cytosol translocation through bioinformatic analyses, protein-protein interaction simulations, and pharmacological inhibitor assays. Collectively, these studies aim to elucidate the molecular mechanisms underlying BMI-1 functions in DIPG, thereby potentially paving the way for the development of targeted therapeutic strategies related to M phase progression.
  • ||||||||||  unesbulin (BMIi-1) / PTC Therap
    Journal:  PTC596-Induced BMI-1 Inhibition Fights Neuroblastoma Multidrug Resistance by Inducing Ferroptosis. (Pubmed Central) -  Jan 26, 2024   
    Of particular interest is the observation that PTC596, alone or in combination with PRIMA-1 and etoposide, significantly reduced GSH levels, increased peroxide production, stimulated lipid peroxidation, and induced ferroptosis. Therefore, these findings suggest that PTC596, by inhibiting BMI-1 and triggering ferroptosis, could be a promising approach to fight chemoresistance.
  • ||||||||||  unesbulin (BMIi-1) / PTC Therap
    Trial completion date, Trial primary completion date:  OU-SCC-PTC-001: Unesbulin in Women With Ovarian Cancer Receiving Neoadjuvant Chemotherapy (clinicaltrials.gov) -  Dec 21, 2023   
    P1,  N=27, Active, not recruiting, 
    The combination therapy of 1000 mg/m IV DTIC q21d and 300 mg unesbulin BIW in a staggered regimen is well tolerated in patients with LMS. Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Jan 2024 --> Jun 2024
  • ||||||||||  unesbulin (BMIi-1) / PTC Therap
    Enrollment closed, Trial completion date, Trial primary completion date, Combination therapy, Metastases:  A Study of Unesbulin (PTC596) in Combination With Dacarbazine in Participants With Advanced Leiomyosarcoma (LMS) (clinicaltrials.gov) -  Feb 10, 2023   
    P1b,  N=41, Active, not recruiting, 
    Trial primary completion date: Dec 2022 --> Dec 2023 Recruiting --> Active, not recruiting | Trial completion date: Aug 2022 --> Jul 2023 | Trial primary completion date: Aug 2022 --> Jul 2023
  • ||||||||||  unesbulin (PTC596) / PTC Therap
    A Rare Case of Metastatic Uterine Leiomyosarcoma to the Pancreas (Crown Ballroom) -  Sep 4, 2022 - Abstract #ACG2022ACG_673;    
    She subsequently received 6 cycles of Docetaxel and gemcitabine followed by pelvic radiation...She was started on Doxorubicin and is currently under evaluation for dacarbazine and the PTC596 trial...EUS-FNA biopsy is the key to diagnosing and differentiating metastatic from new primary lesions. Given the rarity, the treatment for metastatic ULMS to the pancreas is situationally determined and non-standardized, generally is still the combination of surgery, hormonal, and chemotherapy.
  • ||||||||||  unesbulin (PTC596) / PTC Therap
    Rational development of synergistic therapies alongside BMI1 inhibition for group 3 medulloblastoma (Section 23) -  Mar 9, 2022 - Abstract #AACR2022AACR_5388;    
    The combined treatment alongside PTC-596 has demonstrated synergistic efficacy against MB cells with minimal toxicity to hNSCs in vitro and is currently being evaluated in preclinical studies. This study provides the foundation for clinical validation of small-molecule inhibitors synergistic with PTC-596 to improve the durability of remissions and extend survival of patients with treatment-refractory Group 3 MB.
  • ||||||||||  unesbulin (BMIi-1) / PTC Therap
    Enrollment closed, Trial primary completion date:  OU-SCC-PTC-001: Unesbulin in Women With Ovarian Cancer Receiving Neoadjuvant Chemotherapy (clinicaltrials.gov) -  Mar 8, 2022   
    P1b,  N=27, Active, not recruiting, 
    This study provides the foundation for clinical validation of small-molecule inhibitors synergistic with PTC-596 to improve the durability of remissions and extend survival of patients with treatment-refractory Group 3 MB. Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2021 --> Dec 2022
  • ||||||||||  unesbulin (PTC596) / PTC Therap
    Preclinical, Journal:  Preclinical and Early Clinical Development of PTC596, a Novel Small Molecule Tubulin-Binding Agent. (Pubmed Central) -  Feb 11, 2022   
    In a first-in human Phase 1 clinical trial in cancer patients, PTC596 monotherapy drug exposures were compared to those predicted to be efficacious based on mouse models. PTC596 is currently being tested in combination with dacarbazine in a clinical trial in adults with leiomyosarcoma and in combination with radiation in a clinical trial in children with diffuse intrinsic pontine glioma.
  • ||||||||||  cisplatin / Generic mfg.
    [VIRTUAL] Bmi1 Resistance Pathway and Immune Checkpoint Blockade in Lung Cancer (McCormick Place West, Outside Room W375) -  Oct 30, 2021 - Abstract #ASTRO2021ASTRO_1742;    
    These results suggest that chemoradiation therapy leads to the activation of Bmi1 as a resistance mechanism, which in turn results in the activation of inhibitory immune checkpoint PD-L1 leading to immune escape and acquired resistance to immunotherapy. Treatment with PTC-596 demonstrated synergistic benefits to anti-PD-L1 immunotherapy after pre-chemoradiation treatment of preclinical mouse lung tumor model.
  • ||||||||||  cisplatin / Generic mfg.
    Journal, Checkpoint inhibition, PD(L)-1 Biomarker, IO biomarker:  Bmi1 Resistance Pathway and Immune Checkpoint Blockade in Lung Cancer. (Pubmed Central) -  Oct 29, 2021   
    These results suggest that chemoradiation therapy leads to the activation of Bmi1 as a resistance mechanism, which in turn results in the activation of inhibitory immune checkpoint PD-L1 leading to immune escape and acquired resistance to immunotherapy. Treatment with PTC-596 demonstrated synergistic benefits to anti-PD-L1 immunotherapy after pre-chemoradiation treatment of preclinical mouse lung tumor model.
  • ||||||||||  unesbulin (PTC596) / PTC Therap
    Journal:  Diffuse intrinsic pontine glioma cells are vulnerable to mitotic abnormalities associated with BMI-1 modulation. (Pubmed Central) -  Sep 17, 2021   
    Treatment of DIPG stem-like cells with PTC596, a BMI-1 modulator, and IR impairs the kinetics of DNA damage response (DDR)...At the single-cell level, the analysis reveals that BMI-1 pathway is upregulated in undifferentiated cells and positively correlates with stemness in DIPG tumors. Implications: Together, our findings indicate that BMI-1 modulation is associated with mitotic abnormalities, impaired DDR and cell death, supporting the combination of BMI-1 modulation and radiation as a promising novel therapy for children with DIPG.
  • ||||||||||  unesbulin (PTC596) / PTC Therap
    Clinical, Journal:  Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer. (Pubmed Central) -  Aug 12, 2021   
    Post-treatment, MRI analysis showed decreased tumor size, while single cell transcriptomics concomitantly detected near complete ablation of the mutant-KRAS-associated subpopulation, signifying the presence of a pharmacologically targetable, tumor-associated subpopulation. Our findings therefore hold promise for the development of a targeted therapy for KRAS-mutant adenocarcinomas.