- |||||||||| WP1066 / Moleculin, WPD Pharma
Journal: Combining organotypic tissue culture with light-sheet microscopy (OTCxLSFM) to study glioma invasion. (Pubmed Central) - Dec 11, 2023
Using this methodology, we can show that glioblastoma tissue infiltration can be effectively blocked through treatment with arsenic trioxide or WP1066, as well as genetic depletion of the tetraspanin, transmembrane receptor CD9, or signal transducer and activator of transcription 3 (STAT3). With our analysis pipeline, we gain single-cell level, three-dimensional information, as well as insights into the morphological appearance of the tumor cells.
- |||||||||| WP1066 / Moleculin, WPD Pharma
Journal: STAT3 Signalling Drives LDH Up-Regulation and Adiponectin Down-Regulation in Cachectic Adipocytes. (Pubmed Central) - Nov 29, 2023
These modifications are driven by the STAT3 signalling cascade since the inhibition of STAT3 with WP1066 impedes the formation of the cachectic condition and the alteration of lactate dehydrogenase and adiponectin levels. Collectively, these findings show that STAT3 is responsible for the altered lactate dehydrogenase and adiponectin levels that, in turn, could participate in the worsening of this pathology and highlight a step forward in the comprehension of the mechanisms underlying the onset of the cachectic condition in adipocytes.
- |||||||||| liposomal annamycin (L-ANN) / WPD Pharma, Moleculin
Enrollment closed, Enrollment change, Trial primary completion date: Study of Liposomal Annamycin for the Treatment of Subjects With Soft-Tissue Sarcomas (STS) With Pulmonary Metastases (clinicaltrials.gov) - Oct 25, 2023
P1b/2, N=36, Active, not recruiting,
Collectively, these findings show that STAT3 is responsible for the altered lactate dehydrogenase and adiponectin levels that, in turn, could participate in the worsening of this pathology and highlight a step forward in the comprehension of the mechanisms underlying the onset of the cachectic condition in adipocytes. Recruiting --> Active, not recruiting | N=55 --> 36 | Trial primary completion date: Aug 2023 --> May 2024
- |||||||||| WP1066 / Moleculin, WPD Pharma
Trial completion date, Trial initiation date, Trial primary completion date: WP1066 and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma (clinicaltrials.gov) - Oct 4, 2023
P2, N=39, Not yet recruiting,
Recruiting --> Active, not recruiting | N=55 --> 36 | Trial primary completion date: Aug 2023 --> May 2024 Trial completion date: Mar 2026 --> Dec 2028 | Initiation date: Jun 2023 --> Dec 2024 | Trial primary completion date: Mar 2025 --> Dec 2025
- |||||||||| WP1066 / Moleculin, WPD Pharma
Preclinical, Journal, Combination therapy: In vivo targeting of a tumor-antigen encoded DNA vaccine to dendritic cells in combination with tumor-selective chemotherapy eradicates established mouse melanoma. (Pubmed Central) - Aug 9, 2023
Liposomally co-loaded STAT3siRNA and WP1066 (a commercially available inhibitor of the JAK2/STAT3 pathway) were used as cancer therapeutics...Importantly, the findings in tumor growth inhibition studies revealed that only in vivo DC-targeted genetic immunization or only tumor-selective chemotherapy using the presently described systems failed to eradicate the established mouse melanoma. The presently described combination approach is expected to find future applications in combating various malignancies (with well-defined surface antigens).
- |||||||||| olamkicept (FE999301) / Ferring, WP1066 / Moleculin, WPD Pharma
Journal: Blockade of IL-11 Trans-Signaling or JAK2/STAT3 Signaling Ameliorates the Profibrotic Effect of IL-11. (Pubmed Central) - Jul 4, 2023
Fibroblasts co-stimulated with IL-11 and ionomycin showed increased expression of COL3 and phosphorylation of STAT3, which could be inhibited by TJ301 or WP1066...IL-11 induces fibrosis in SSc by regulating the trans-signaling pathway. Blockage of sgp130Fc or inhibition of the JAK2/STAT3 pathway could ameliorate the profibrotic effect of IL-11.
- |||||||||| liposomal annamycin (L-ANN) / WPD Pharma, Moleculin
Journal: Anthracycline-induced cardiotoxicity - are we about to clear this hurdle? (Pubmed Central) - May 16, 2023
To prevent cardiotoxicity, several strategies are being followed: (i) angiotensin-converting enzyme inhibitors, sartans, beta-blockers, aldosterone antagonists, and statins; (ii) iron chelators; and (iii) by development of new anthracycline derivatives with little or no cardiotoxicity. This review will discuss clinically evaluated doxorubicin analogues that were developed as potentially non-cardiotoxic anticancer agents and include recent development of a novel liposomal anthracycline (L-Annamycin) for the treatment of soft-tissue sarcoma metastatic to the lung and acute myelogenous leukaemia.
- |||||||||| liposomal annamycin (L-ANN) / WPD Pharma, Moleculin
Exploration of Annamycin Organotropism to Target Primary and Metastatic Liver Cancers (Section 15; Poster Board #25) - Mar 14, 2023 - Abstract #AACR2023AACR_7348;
Expanded studies to assess L-ANN activity in different tumor liver metastasis models as well as HCC models are being planned. It should be noted that L-ANN is currently undergoing clinical trials in patients with pulmonary metastasis soft tissue sarcoma and acute myeloid leukemia.
- |||||||||| WP1066 / Moleculin, WPD Pharma
Trial completion, Enrollment change, Trial completion date, Trial primary completion date: WP1066 in Children With Refractory and Progressive or Recurrent Malignant Brain Tumors (clinicaltrials.gov) - Feb 21, 2023
P1, N=10, Completed,
Conclusion(s): Thus, the application of WP1066 as a regulator of STAT3 phosphorylation may be a promising new neuroprotection strategy in neonatal HIE. Recruiting --> Completed | N=36 --> 10 | Trial completion date: Jul 2023 --> Feb 2023 | Trial primary completion date: Jul 2023 --> Feb 2023
- |||||||||| liposomal annamycin (L-ANN) / WPD Pharma, Moleculin
Trial completion, Enrollment change, Trial completion date, Trial primary completion date: Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - Jan 20, 2023
P1/2, N=20, Completed,
Active, not recruiting --> Completed | N=80 --> 53 Active, not recruiting --> Completed | N=75 --> 20 | Trial completion date: Dec 2022 --> Feb 2022 | Trial primary completion date: Sep 2022 --> Feb 2022
- |||||||||| WP1122 / Moleculin, CNS Pharma, WPD Pharma
Enrollment closed: Study to Assess the Safety and Pharmacokinetics of WP1122 in Healthy Volunteers (clinicaltrials.gov) - Nov 3, 2022
P1a, N=80, Active, not recruiting,
Active, not recruiting --> Completed | N=75 --> 20 | Trial completion date: Dec 2022 --> Feb 2022 | Trial primary completion date: Sep 2022 --> Feb 2022 Recruiting --> Active, not recruiting
- |||||||||| zuclomiphene (VERU-944) / Veru Inc, WP1066 / Moleculin, WPD Pharma
Biomarker, Journal: Experimental verification and validation of immune biomarkers based on chromatin regulators in ischemic stroke. (Pubmed Central) - Sep 20, 2022
Molecular docking simulations revealed that mevastatin, WP1066, cladribine, trichostatin A, mequitazine, and zuclomiphene may be potential immunomodulatory drugs for IS. Overall, the results of this study contribute to the identification of CR-related immune therapeutics target in IS and provide an important reference for further research.
- |||||||||| WP1066 / Moleculin, WPD Pharma
Journal, PD(L)-1 Biomarker, IO biomarker: Induction of M-MDSCs with IL6/GM-CSF from adherence monocytes and inhibition by WP1066. (Pubmed Central) - Jun 29, 2022
In conclusion, the present study described the generation of monocytic MDSCs from adherence monocytes and the inhibition of STAT3 inhibitor WP1066 on the induced MDSCs. The present study contributed to the development of a new clinical drug, WP1066 targeting MDSC.
- |||||||||| WP1066 / Moleculin, WPD Pharma
Preclinical, Journal: WP1066 induces cell death in a schwannomatosis patient-derived schwannoma cell line. (Pubmed Central) - Jun 24, 2022
It reduced cell viability and STAT-3 phosphorylation and induced expression of markers for both necroptosis and caspase-dependent cell death. The results demonstrate feasibility in creating patient-derived cell lines for use in precision medicine studies.
- |||||||||| WP1066 / Moleculin, WPD Pharma
Journal: Naringin Regulates Microglia BV-2 Activation and Inflammation via the JAK/STAT3 Pathway. (Pubmed Central) - Jun 4, 2022
BV-2 cells were obtained from the China Center for Type Culture Collection and randomly divided into five treatment groups: control, model, NAR (10 μM), WP1066 (5 μM), and NAR + WP1066...NAR treatment inhibited the proliferation, migration, and inflammation of BV-2 cells as well as the activation of microglia to the M1 phenotype. Conversely, NAR treatment promoted the activation of microglia to the M2 phenotype and enhanced the phagocytic function of BV-2 cells by regulating the activity of the JAK/STAT3 pathway.
- |||||||||| WP1122 / Moleculin, CNS Pharma, WPD Pharma
Enrollment open, Trial completion date, Trial primary completion date: Study to Assess the Safety and Pharmacokinetics of WP1122 in Healthy Volunteers (clinicaltrials.gov) - May 12, 2022
P1a, N=80, Recruiting,
WP1066 had an MFD identified at 8 mg/kg which is the target allometric dose based on prior preclinical modeling in combination with radiation therapy and a Phase II study is being planned for newly diagnosed MGMT promoter unmethylated glioblastoma patients. Trial completion date: Jul 2022 --> Oct 2022 | Trial primary completion date: Jul 2022 --> Oct 2022 | Not yet recruiting --> Recruiting
- |||||||||| liposomal annamycin (L-ANN) / WPD Pharma, Moleculin
Enrollment closed, Trial primary completion date: Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - Apr 6, 2022
P1/2, N=75, Active, not recruiting,
Trial completion date: Jul 2022 --> Oct 2022 | Trial primary completion date: Jul 2022 --> Oct 2022 | Not yet recruiting --> Recruiting Recruiting --> Active, not recruiting | Trial primary completion date: Feb 2022 --> Sep 2022
- |||||||||| WP1066 / Moleculin, WPD Pharma
Trial completion, Trial completion date, Trial primary completion date, Metastases: STAT3 Inhibitor WP1066 in Treating Patients With Recurrent Malignant Glioma or Progressive Metastatic Melanoma in the Brain (clinicaltrials.gov) - Mar 23, 2022
P1, N=8, Completed,
Recruiting --> Active, not recruiting | Trial primary completion date: Feb 2022 --> Sep 2022 Active, not recruiting --> Completed | Trial completion date: Jul 2022 --> Mar 2022 | Trial primary completion date: Jul 2022 --> Mar 2022
- |||||||||| liposomal annamycin (L-ANN) / WPD Pharma, Moleculin
New approach to target metastatic colorectal cancer organotropism with L-Annamycin (Section 27) - Mar 9, 2022 - Abstract #AACR2022AACR_5994;
P1b/2
Our previous in vivo studies of L-ANN in sarcoma lung metastasis models already led to initiation of multicenter clinical studies (NCT04887298). This study demonstrating L-ANN efficacy in CRC models provides convincing evidence for further preclinical development aimed at initiation of clinical studies in CRC metastatic patients.
- |||||||||| WP1066 / Moleculin, WPD Pharma
JAK-independent STAT5 signaling as a node of therapeutic vulnerability in glioblastoma (Section 5) - Mar 9, 2022 - Abstract #AACR2022AACR_2834;
Inhibition of Src family kinases (SFK), a family of upstream signaling effectors of the JAK/STAT pathway, attenuates both STAT3 and STAT5 activation. These results suggest that activation of STAT5 may provide a therapeutic escape mechanism to JAK-STAT3 inhibition in GBM, necessitating dual STAT3 and STAT5 inhibition to successfully inhibit the distinct oncogenic signals transmitted by STAT3 and STAT5 to promote GBM cell survival and resistance.
- |||||||||| WP1122 / Moleculin, CNS Pharma, WPD Pharma
Trial initiation date: Study to Assess the Safety and Pharmacokinetics of WP1122 in Healthy Volunteers (clinicaltrials.gov) - Feb 15, 2022
P1a, N=80, Not yet recruiting,
These results suggest that activation of STAT5 may provide a therapeutic escape mechanism to JAK-STAT3 inhibition in GBM, necessitating dual STAT3 and STAT5 inhibition to successfully inhibit the distinct oncogenic signals transmitted by STAT3 and STAT5 to promote GBM cell survival and resistance. Initiation date: Jan 2022 --> Apr 2022
- |||||||||| WP1122 / Moleculin, CNS Pharma, WPD Pharma
Journal, Epigenetic controller: Synergistic Anticancer Effect of Glycolysis and Histone Deacetylases Inhibitors in a Glioblastoma Model. (Pubmed Central) - Dec 27, 2021
Over the last decade, we have seen tremendous progress in research on 2-deoxy-D-glucose (2-DG) and its analogs...Novel 2-DG analogs such as WP1122 and others have revived the old concept of glycolysis inhibition as an effective anticancer strategy...We focused our efforts on the development of new combinations of anticancer agents coupled with 2-DG and its derivatives, targeting glioblastoma, which is in desperate need of novel approaches and therapeutic options and is particularly suited to glycolysis inhibition, due to its reliance on aerobic glycolysis. Herein, we present evidence that a combined treatment of 2-DG analogs and modulation of histone deacetylases (HDAC) activity via HDAC inhibitors (sodium butyrate and sodium valproate) exerts synergistic cytotoxic effects in glioblastoma U-87 and U-251 cells and represents a promising therapeutic strategy.
- |||||||||| WP1066 / Moleculin, WPD Pharma
Clinical, Journal: Radiation with STAT3 blockade triggers dendritic cell-T cell interactions in the glioma microenvironment and therapeutic efficacy. (Pubmed Central) - Dec 16, 2021
Herein, we present evidence that a combined treatment of 2-DG analogs and modulation of histone deacetylases (HDAC) activity via HDAC inhibitors (sodium butyrate and sodium valproate) exerts synergistic cytotoxic effects in glioblastoma U-87 and U-251 cells and represents a promising therapeutic strategy. This study indicates that the combination of STAT3 inhibition and WBRT enhances the therapeutic effect against gliomas in the CNS by inducing dendritic cell and T cell interactions in the CNS tumor.
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