Overall, the findings suggest that compound 4b has a promising future as a starting point for the development of new anticancer drugs.

P2, N=235, Not yet recruiting, Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.

P2, N=67, Completed, Curacle Co., Ltd. | Active, not recruiting --> Completed | Phase classification: P2a --> P2 | Trial completion date: Mar 2024 --> Jun 2023 | Trial primary completion date: Feb 2024 --> May 2023

P3, N=420, Recruiting, Summit Therapeutics

P1, N=48, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting | Trial primary completion date: Apr 2025 --> Nov 2024

P2, N=44, Not yet recruiting, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Here, we develop a smart DNA-based nanodrug, termed Endo-rDFN, by precisely assembling the antiangiogenic agent, endostar (Endo), into a reconfigurable DNA framework nanotube (rDFN) that could recognize tumor-overexpressed nucleolin to achieve the targeted delivery and controllable release of Endo. Endo-rDFN can not only effectively enhance the tumor-targeting capability of Endo and maintain its efficient accumulation in tumor tissues but also achieve on-demand release of Endo at tumor sites via the specific DNA aptamer for tumor-overexpressed nucleolin, named AS1411. We also found that Endo-rDFN exhibited significant inhibition of angiogenesis and tumor growth, while also providing effective protection against multiorgan injury (heart, liver, spleen, kidney, lung, etc.) to some extent, without compromising the function of these organs. Our study demonstrates that rDFN represents a promising vector for reducing antiangiogenic therapy-induced multiorgan injury, highlighting its potential for promoting the clinical application of antiangiogenic agents.

P2, N=30, Recruiting, Tianjin Medical University Cancer Institute and Hospital

P2, N=146, Recruiting, Ludwig-Maximilians - University of Munich | Not yet recruiting --> Recruiting | Phase classification: P2a --> P2 | Trial completion date: Jan 2027 --> Jul 2027 | Initiation date: Oct 2023 --> Apr 2024 | Trial primary completion date: Oct 2026 --> Apr 2027

P1, N=45, Recruiting, Boehringer Ingelheim | Active, not recruiting --> Recruiting | Trial primary completion date: Aug 2024 --> Apr 2025

On the contrary, some patients with mucosal, acral or KIT-mutant melanoma may benefit from TKI-based therapies. Further studies focused on biomarker discovery and randomized trials are necessary to better understand the role of VEGFR1-3 as a therapeutic target in melanoma.

P2, N=60, Completed, AbbVie | Active, not recruiting --> Completed

P2, N=120, Recruiting, Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.

P1, N=122, Recruiting, HC Biopharma Inc. | Not yet recruiting --> Recruiting

P2, N=296, Recruiting, Akeso | Trial primary completion date: Mar 2024 --> Dec 2024

P1, N=47, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

Mechanistically, CPD-002 hindered the activation of VEGFR2/PI3K/AKT pathway in VEGF-induced HUVECs and AIA rat synovium, as evidenced by reduced p-VEGFR2, p-PI3K, and p-AKT protein levels alongside elevated PTEN protein levels. Totally, CPD-002 showed anti-rheumatoid effects via attenuating angiogenesis through the inhibition of the VEGFR2/PI3K/AKT pathway.

P1, N=122, Not yet recruiting, HC Biopharma Inc.

P2, N=36, Recruiting, Theratocular Biotek Co. | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2023 --> Mar 2024

P1, N=19, Active, not recruiting, National Cancer Institute (NCI)

P2, N=16, Recruiting, Nanjing First Hospital, Nanjing Medical University

P1/2, N=515, Not yet recruiting, Sinocelltech Ltd.

P1/2, N=233, Recruiting, Akeso | N=148 --> 233

P2/3, N=300, Recruiting, AbbVie | Phase classification: P2b --> P2/3

P2, N=170, Active, not recruiting, OnQuality Pharmaceuticals (USA) LLC | Recruiting --> Active, not recruiting | Trial completion date: Mar 2024 --> Jun 2024 | Trial primary completion date: Oct 2023 --> Feb 2024

In hematoxylin and eosin and TUNEL staining, 3 weeks of CPC+PLGA+ENDO-treatment yielded higher tissue necrosis and apoptosis than other groups; computed tomography and magnetic resonance imaging results showed the posterior edge bone damage reduced as a result of the CPC+PLGA+ENDO grafting in vertebral pedicle. Overall, the feasibility and reliability of CPC-loaded Endostar in the treatment of bone metastasis in lung cancer were investigated in this study, so as to promote the basic research and treatment of bone metastasis in lung cancer and other malignant tumors.

P2, N=126, Completed, Xinqiao Hospital of Chongqing | Unknown status --> Completed

Here, we developed a trifunctional fusion protein, DR30206, composed of Bevacizumab (an antibody against VEGF), and a variable domain of heavy chain of heavy chain antibody (VHH) against PD-L1 and the extracellular domain (ECD) protein of TGF-β receptor II (TGF-β RII), which are fused to the N- and C-terminus of Bevacizumab, respectively. Finally, in vivo experiments showed that the antitumor activity of DR30206 was superior to those of monoclonal antibody of PD-L1 or VEGF, PD-L1 and TGF-β bispecific antibody or the combination inhibition of PD-L1 and VEGF. Our findings suggest there is a great potential for DR30206 to become a therapeutic for the treatment of multiple cancer types, especially lung cancer, colon adenocarcinoma and breast carcinoma.

P1/2, N=250, Recruiting, Akeso | N=160 --> 250 | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2023 --> Aug 2024

The juxtamembrane inhibition of VEGFR1 suppresses its basal phosphorylation even at high receptor concentrations and transiently stabilizes tyrosine phosphorylation after ligand stimulation. We conclude that a subtle imbalance in phosphatase activation or removing juxtamembrane inhibition is sufficient to induce ligand-independent activation of VEGFR1 and sustain tyrosine phosphorylation.

P2, N=104, Recruiting, Akeso | Trial completion date: Jan 2025 --> Dec 2026 | Trial primary completion date: Oct 2022 --> Dec 2024

Endostar combined with cisplatin might exert anti-tumor effects by down-regulating the expression of METTL3 and FMOD.

In this work, the cytotoxicity of monoclonal antibody (Cetuximab, Ce) and Fenbendazole (Fen), as well as their combination therapy were tested with the MTT assay. Furthermore, the cell cycle analysis and Annexin V apoptosis assay were carried out for Ce, Fen, and a combination of them. In addition, the molecular docking studies were used to describe the molecular levels of interactions for both (Fen and colchicine) or (Fen and sorafenib) within the binding pockets of the colchicine binding site (CBS) and vascular endothelial growth factor-2 receptor (VEGFR-2), respectively.

These findings suggest CU06-1004 as a potential therapeutic agent for folic acid-induced AKI.

P2, N=36, Not yet recruiting, Harbin Medical University

P2, N=50, Not yet recruiting, Harbin Medical University

P1, N=25, Recruiting, Chengdu Origen Biotechnology Co., Ltd.

P1, N=45, Not yet recruiting, Caregen Co. Ltd.

Exosomal ANGPTL1 suppressed GBM angiogenesis by inhibiting the VEGFA/VEGFR2/Akt/eNOS axis.

Compound 12b had potent activity against VEGFR-2 with an IC value of 0.063 ± 0.003 μM, compared to sunitinib with IC = 0.035 ± 0.012 μM...Cell cycle and apoptosis investigations showed that compound 12b could stop the cell cycle at the S phase and significantly increase total apoptosis in the MDA-MB-468 cell line by 18.98-fold compared to the control. Moreover, compound 12b increased the caspase-3 level in the MDA-MB-468 cell line by 7.32-fold as compared to the control.

P1, N=182, Recruiting, Zhejiang Doer Biologics Co., Ltd. | Not yet recruiting --> Recruiting

The findings revealed that almost all of the compounds had considerable binding to AURKA and VEGFR-2 residues, with binding affinities ranging from -9.8 to -7.9 kcal/mol. Consequently, the results of the biological investigations and the docking scores demonstrated that thiazolidinone molecule 5e containing 4-chlorophenyl substituent may be considered as a potential moiety for glioblastoma cancer treatments.