P1, N=16, Completed, APR Applied Pharma Research s.a. | Recruiting --> Completed

Compound 5 was the most active derivative against HepG-2 and HuH-7 cell lines with IC50 = 0.75 ± 0.04 and 3.43 ± 0.16 μM, respectively, in contrast to Sorafenib which shows IC50 values of 5.23 ± 0.31 and 4.58 ± 0.21 μM, respectively...Hybrid 5 stops HepG-2's cell cycle at the S phase 48.02 % higher than untreated. Docking experiments assessed AKT and VEGFR2 binding patterns.

P2, N=109, Active, not recruiting, Cardiol Therapeutics Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Nov 2024 --> Jan 2025

P2/3, N=110, Not yet recruiting, Cardiol Therapeutics Inc.

Compound 16c boosted the level of the apoptotic caspase-3 and inhibited the level of TNF-α and IL-6 in tumor cells. Molecular docking and molecular dynamics (MD) simulations indicated the outstanding binding potential of compound 16c against VEGFR-2. Compound 16c is a good candidate for the creation of a novel antiangiogenic lead anticancer medication.

Finally, we recommended KGs-guided four repurposable drug molecules (Fluoxetine, Vatalanib, TGX221 and RO3306) against GBM through molecular docking, drug likeness, ADMET analyses and molecular dynamics simulation studies. Thus, the discoveries of this study could serve as valuable resources for wet-lab experiments in order to take a proper treatment plan against GBM.

We utilized MT to treat cardiotoxin (CTX) injury-induced skeletal muscle inflammation in C57BL6/J mice...However, after treatment with MT, S100A9 protein expression and the numbers and activity of Ly6g+/Mpo+ neutrophils were significantly inhibited, thus reducing the inflammatory cytokine levels and exerting an anti-inflammatory effect by early clearing neutrophils. MT can mitigate localized inflammation induced by injured skeletal muscle, achieved by decreasing S100A9 protein expression and clearing neutrophils in mice, which may help advance therapeutic strategies for skeletal muscle localized inflammation.

This review discusses several potent alkaloids, such as homoharringtonine, chaetominine, matrine, and jerantinine B, which induce apoptosis, cell cycle arrest, and autophagy and inhibit signaling pathways including PI3K/Akt/mTOR, MAPK, and NF-κB...In addition, targeting leukemia stem cells (LSCs) with alkaloids such as zalypsis offers promise due to its ability to induce apoptosis without significantly affecting normal hematopoietic stem cells...For example, jerantinine B targets AML cells, while vincristine has shown success in lymphocytic leukemia...However, adverse effects such as neutropenia and hepatotoxicity necessitate careful management. Collectively, these findings emphasize the need for further research into alkaloid-based combination therapies to enhance efficacy and minimize toxicity, providing a promising avenue for innovative leukemia treatments.

Moreover, drug-likeness and pre-ADMET evaluation showed that the compounds had suitable drug properties. This study may be a new milestone in terms of the promising importance of carbonitrile-substituted pyrazole-tosyl amide scaffolds as apoptosis-inducing agents for cancer therapy in the future.

P2, N=25, Completed, Cardiol Therapeutics Inc. | Active, not recruiting --> Completed

Our findings elucidate that TWEAK facilitates keratinocyte apoptosis by augmenting caspase-3 activity, leading to DSG1/3 depletion and apoptosis in pemphigus. Importantly, naloxone can counter TWEAK-induced apoptosis in pemphigus pathogenesis, offering a potential therapeutic intervention.

Moreover, DCM-C + E and CM-C + E showed the highest toxicity in KG-1a and EoL-1 cells. Using two peptides likely improves the probability of micelles binding to the FLT3 receptor and induces cytotoxicity in leukemic stem cells.

P=N/A, N=74, Active, not recruiting, Poitiers University Hospital | Trial primary completion date: Jul 2024 --> Jul 2026

P2, N=25, Active, not recruiting, Cardiol Therapeutics Inc. | Trial completion date: Dec 2024 --> Sep 2024 | Trial primary completion date: Nov 2024 --> Jun 2024

This was followed by the induction of mitochondrial intrinsic apoptosis via the activation of caspases 9 and 3, cleavage of PARP, and the suppression of pro-apoptotic Bid. Astilbin-induced p53-mediated apoptosis in OSCC cells as herbal medicinal ingredients.

Computational in silico modeling of the new hybrids revealed that they presented acceptable physicochemical values as well as drug-like characteristics, which may introduce them as drug-like candidates. The study proved that compound X1 might be a novel candidate for the development of anticancer agents as it presents antiproliferative activity mediated by apoptosis.

P2, N=8, Terminated, Sanofi | Phase classification: P1b/2 --> P2

P2, N=25, Active, not recruiting, Cardiol Therapeutics Inc. | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Nov 2024

Our findings point to significant anticancer activities of Schiff bases tethered OSe agents, suggesting their promising potential for development as effective anticancer drugs.

Our results highlight the potential of Utt-B as an effective chemosensitizer, which can augment the efficacy of Sor against HCC and circumvent Sor-induced toxic side effects. Moreover, this is the first and only report to date on the chemosensitizing potential of Utt-B and the only report that demonstrates the therapeutic efficacy and pharmacological safety of a novel combinatorial regimen involving Utt-B and Sor for combating HCC.

P2, N=64, Not yet recruiting, Sanofi | Initiation date: Jun 2024 --> Nov 2024

MiR-34b promotes cellular senescence and oxidative stress by targeting TWIST1, a known oncogene and EMT regulator. This study delved into the mechanism of miR-34b-mediated tumor suppression and provided novel insights for development of miR-34b based therapeutics for cervical cancer.

P1, N=16, Recruiting, APR Applied Pharma Research s.a. | Not yet recruiting --> Recruiting

The antimetastatic effect of 4d was associated with the upregulation of DUSP1. Overall, these compelling results underscore the tremendous potential of 4d for treating TNBC.

In vivo study illustrated the anticancer activity of compound 2n by reduction of tumor mass and volume, and the tumor inhibition ratio reached 56.1% with an improvement of hematological parameters. Accordingly, compound 2n can be further developed as a selective target-oriented chemotherapeutic against breast cancer.

P2, N=100, Cardiol Therapeutics Inc.

P1, N=16, Not yet recruiting, APR Applied Pharma Research s.a.

P1, N=140, Recruiting, VA Office of Research and Development | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: May 2024 --> May 2025

P3, N=534, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting | Trial primary completion date: May 2024 --> Nov 2024

On the other hand, molecular docking and ADMET studies were performed for the examined candidates as well. Overall, our findings point to significant anticancer activities of the organoselenium tethered amidic acids, suggesting their promising cytotoxic potential as effective anticancer drugs.

Taken together, ARID1A loss significantly heightens sensitivity to RITA in CRC, revealing a novel synthetic lethal interaction between ARID1A and RITA. These findings present a promising therapeutic approach for colorectal cancer characterized by ARID1A loss-of-function mutations.

P1, N=14, Completed, Keystone Nano, Inc | Unknown status --> Completed | N=24 --> 14 | Trial completion date: Aug 2019 --> Nov 2023 | Trial primary completion date: Aug 2019 --> Aug 2023

P2, N=71, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting

P=N/A, N=74, Active, not recruiting, Poitiers University Hospital | Recruiting --> Active, not recruiting

A completely new activity of FOXM1, mediated through steroid/cholesterol biosynthetic process and protein secretion in cancer cells was also detected. Collectively, STL001 offers intriguing translational opportunities as combination therapies targeting FOXM1 activity in a variety of human cancers driven by FOXM1.

P2, N=20, Recruiting, Sun Yat-sen University

The ideal environment for tyrosine kinase inhibitor therapy is produced by a favorable oxidative status. We discuss the latest studies that aim to manipulate the redox system to alter the apoptosis of cancerous cells.

Adjuvant treatment for Glioblastoma Grade 4 with Temozolomide (TMZ) inevitably fails due to therapeutic resistance, necessitating new approaches...We assessed TMZ, Methotrexate (MTX), and Cytarabine (Ara-C) (apoptosis inducers) combined with XPO1/Bcl-2/Mcl-1-inhibitors (apoptosis rescue) in GB cell lines and primary GB stem-like cells (GSCs)...TMZ, MTX, and Ara-C combined with E, V, and A evidenced highly lethal effects when combined. As no significant cell death induction in mouse brain slices was observed, we conclude that this drug combination is effective in vitro and expected to have low side effects in vivo.

P2, N=64, Not yet recruiting, Sanofi

Furthermore, GIC-20 also enhanced the sensitivity of resistant MIA-PaCa-2-AMG510R cells to AMG510, suggesting the great potential of GIC-20 in overcoming the acquired resistance of KRASG12C inhibitors. Overall, GIC-20 represents a novel dual ferroptosis/apoptosis inducer warranting further development for cancer therapeutics and overcoming drug resistance.

P2, N=25, Active, not recruiting, Cardiol Therapeutics Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2024 --> Jun 2024

P1, N=90, Recruiting, D. Walter Wray