CEP synergistically promoted MP pharmacodynamics to decrease the cell viability of the mitogen-activated PBMCs, possibly via inhibiting P-glycoprotein function and potentiating GC receptor translocation. The present study provides new evidence of the therapeutic effect of Cepharanthin® alone or in combination with GC for the management of chronic ITP.

Further experiments showed that As2 overcomes multidrug resistance and sensitizes drug-resistant leukemia and lymphoma cell lines to treatments with the common cytostatic drugs vincristine, daunorubicin, and cytarabine at low micromolar concentrations. Downregulation of XIAP (x-linked inhibitor of apoptosis protein) and apoptosis induction independent of Bcl-2 (B-cell lymphoma 2) and caspase-3 expression levels suggest the activation of additional apoptosis-promoting mechanisms. Due to the selective apoptosis induction, the synergistic effects with common anti-cancer drugs, and the ability to overcome multidrug resistance in vitro, As2 represents a promising candidate for further preclinical investigations with respect to refractory malignancies.

P=N/A, N=74, Recruiting, Peking University People's Hospital | Trial primary completion date: Feb 2024 --> Dec 2024

P1, N=40, Completed, Wake Forest University Health Sciences | Unknown status --> Completed | Phase classification: P2 --> P1

Remarkably, the enhanced KG1a cell sensitivity to DNR after SB203580 pretreatment was associated with an increased upregulation of miR-328-3p and slight downregulation of miR-26b-5p, compared to DNR effect. Altogether, these findings could contribute to the development of a new therapeutic strategy by targeting the p38 MAPK pathway to improve treatment outcomes in patients with refractory or relapsed AML.

P2, N=42, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Apr 2024 --> Sep 2024

P1, N=35, Completed, Washington University School of Medicine | Active, not recruiting --> Completed

However, despite the massive increase in the number of marine natural products classified as 'anticancer leads,' most of which correspond to general cytotoxic agents, and only a few have been characterized regarding their molecular targets and mechanisms of action. The current review presents a critical analysis of inhibitors of HIF-1 and HIF-2 and hypoxia-selective compounds that have been sourced from marine organisms and that might act as new chemotherapeutic candidates or serve as templates for the development of structurally similar derivatives with improved anticancer efficacy.

P=N/A, N=37, Not yet recruiting, First Affiliated Hospital Xi'an Jiaotong University

Analogue 3 exhibited superior in vivo efficacy to echinomycin without significant toxicity in mouse xenograft model. The low dose of 3 needed to be efficacious in vivo is also noteworthy and our data suggest that 3 is an attractive and potentially novel agent for the treatment of colon cancer.

P3, N=154, Recruiting, Zhongnan Hospital

In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1)...The body weight loss was similar in all mice treated with any DOX formulation, suggesting no difference in toxicity. In conclusion, LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue.

DNR induces Cyr61 production in B-ALL cells, and increased Cyr61 levels reduce the chemosensitivity of B-ALL cells. Consequently, targeting Cyr61 or related ATM signaling pathway may present a promising treatment strategy to enhance the chemosensitivity of patients with B-ALL.

P=N/A, N=78, Recruiting, Ruijin Hospital

Valproate can affect drug resistance in gastric cancer via a unique mechanism independent of MDR1 expression.

This case suggests that dose capping of anthracyclines in the treatment of newly diagnosed AML may be an effective and safe treatment alternative in those with extreme BMI elevations beyond what has been studied in the literature. Given the increasing incidence of morbid obesity, further studies are needed to confirm appropriate dosing of anthracycline-based regimens at upper BMI extremes (>60 kg/m2).

Significantly, PL suppressed AML development in a mouse xenograft model, and its combination with current AML treatments (cytarabine, daunorubicin and azacytidine) had synergistic effects, indicating translational therapeutic potential. Taken together, these data position PL as a novel anti-AML candidate drug that can target leukaemia stem/progenitors and is amenable to combinatorial therapeutic strategies.

P=N/A, N=90, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Recruiting

To achieve this, we introduced genes from the aclarubicin biosynthetic pathway encoding the sugar N-methyltransferases AclP and AknX2. DoxA is the key enzyme that determines the efficiency of the biosynthesis of N,N-dimethylated anthracyclines, and engineering of this enzyme will be a major step forwards towards the efficient production of more N,N-dimethylated anthracyclines, including N,N-dimethyldoxorubicin. This study provides valuable insights into the biosynthesis of clinically relevant daunorubicin derivatives, highlighting the importance of combinatorial biosynthesis.

P1, N=31, Terminated, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | N=50 --> 31 | Not yet recruiting --> Terminated; The sponsor has adjusted its R&D strategy.

P1, N=38, Terminated, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | N=63 --> 38 | Recruiting --> Terminated | Trial primary completion date: Mar 2022 --> Jun 2023; The sponsor has adjusted its R&D strategy.

P2, N=45, Terminated, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | N=81 --> 45 | Unknown status --> Terminated; The sponsor has adjusted its R&D strategy.

P1/2, N=41, Terminated, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | N=104 --> 41 | Not yet recruiting --> Terminated; The sponsor has adjusted its R&D strategy.

P1, N=56, Terminated, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | N=30 --> 56 | Trial completion date: Jan 2024 --> May 2023 | Recruiting --> Terminated | Trial primary completion date: Jan 2022 --> May 2023; The sponsor has adjusted its R&D strategy.

P1, N=45, Completed, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | Not yet recruiting --> Completed | N=30 --> 45 | Trial completion date: Apr 2024 --> Oct 2023 | Trial primary completion date: Apr 2022 --> Oct 2023

P1, N=21, Terminated, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | N=30 --> 21 | Recruiting --> Terminated; The sponsor has adjusted its R&D strategy.

TRIM59 expression interference may enhance the chemosensitivity of K562 cells to DNR, and its mechanism may be related to the regulation of Wnt/β-catenin signaling pathway.

The results of the study have shown that cytotoxic drugs can alter the expression of antigens that are important for immunotherapy. Importantly, daunorubicin, prednisolone and vincristine caused down-modulation of CD19 and CD58, suggesting that these drugs are better avoided during bridging therapy prior to bispecific antibodies or CAR-T cell therapy. In addition, immunophenotypic changes on blast cells induced by different drugs could also influence risk-based treatment assignment.

P2, N=28, Terminated, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | N=73 --> 28 | Recruiting --> Terminated; The sponsor has adjusted its R&D strategy.

P1/2, N=1, Terminated, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | N=90 --> 1 | Not yet recruiting --> Terminated; Adjust the research strategy.

Compound 6l decreased EGFR protein concentration by a 6.10-fold change, compared to imatinib as a reference standard...Besides, the DNA fragmentation images described the great potential of both candidates 6a and 6l in inducing DNA degradation at lower concentrations compared to etoposide and doxorubicin. Moreover, compound 6l, with the most promising EGFR/TOPO II inhibition and DNA intercalation, was selected for further investigation for its apoptosis induction ability by measuring caspases 3, 7, 8, and 9, Bax, p53, MMP2, MMP9, and BCL-2 proteins. Additionally, molecular docking was used to explain the SAR results based on the differences in the molecular features of the investigated congeners and the target receptors' topology.

Recently, several DNA intercalators have attracted much interest given their ability to inhibit RNA Polymerase I transcription (BMH-21), evict histones (Aclarubicin) or induce chromatin trapping of FACT (Curaxin CBL0137)...These DNA intercalators have a cumulative impact on general transcription machinery by inducing accumulation of topological defects and impacting nuclear chromatin. Therefore, their cytotoxic capabilities may be the result of compounding deleterious effects on chromatin homeostasis.

P1, N=29, Completed, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | Not yet recruiting --> Completed

P2, N=104, Recruiting, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | Not yet recruiting --> Recruiting

P1, N=18, Active, not recruiting, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Active, not recruiting

P1/2, N=30, Recruiting, Huijing Wu

P2, N=28, Recruiting, Wuhan Union Hospital, China

Cardiotoxicity was induced in rabbits via daunorubicin administration (daunorubicin, 3 mg/kg/week; for five and 10 weeks), while the control group received saline solution...Furthermore, plasma levels of miR-34a-5p were strongly correlated with the myocardial expression of this miRNA. To the best of our knowledge, this is the first study that describes alterations in miRNA expression in the myocardium during the transition from subclinical, ANT-induced cardiotoxicity to an overt cardiotoxic phenotype; we also revealed how these changes in miRNA expression are strongly correlated with quantitative markers of cardiotoxicity.

P=N/A, N=50, Recruiting, The First Affiliated Hospital with Nanjing Medical University

P2, N=42, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Jan 2024 --> Apr 2024

The accumulation of MOLM-13 cells in the CHT was reduced in larvae receiving EHop-016 treatment. Our findings demonstrate that targeting Rac1 in AML holds promise as a complementary treatment to established chemotherapy and should be further investigated.

Similar overall best response rates were observed in patients receiving induction with daunorubicin combined with cytarabine arabinoside (daunorubicin + ara-C) (74% [23/31]) or FLAG-IDA/NOVE-HiDAC (78% [39/50], p=0.78)...Mutations in TP53 (OR 8.2 [95% CI 2.01, 37.1], p=0.004) and RAS pathway (OR 5.1 [95%CI 1.2, 23.7], p=0.03) were associated with inferior treatment response for intensively-treated patients, and poorer performance status (ECOG) was associated with inferior treatment response in both intensively- (OR 10.4 [95%CI 2.0, 78.5], p=0.009) and nonintensively-treated groups (OR 12 [95%CI 2.04, 230.3], p=0.02). In patients with paired samples prior to and after therapy (N=26), there was a significant residual mutation burden remaining irrespective of response to blast-reduction therapy.