A Phase 1 Multi-center, Open-label Dose Escalation and Expansion Study of PCA062 Administered Intravenously in Adult Patients With p-CAD Positive Tumors

A first-in-human sttudy using PCA062 in patients with p-CAD positive solid tumors.

Start Date15 Apr 2015

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

100 Clinical Results associated with PCA-062

100 Translational Medicine associated with PCA-062

100 Patents (Medical) associated with PCA-062

Literatures (Medical) associated with PCA-062

01 Dec 2024·Carbohydrate Polymers

Dihydromyricetin-loaded oxidized polysaccharide/L-arginine chitosan adhesive hydrogel promotes bone regeneration by regulating PI3K/AKT signaling pathway and MAPK signaling pathway

Article

Author: Wei, Hewei ; Liu, Wencong ; Ding, Qiteng ; Wang, Yue ; Sun, Shuwen ; Ding, Chuanbo ; Wang, Ning ; Yang, Jiali ; Zhang, Shuai ; Zhang, Lifeng

Bone defects caused by trauma, infection and congenital diseases still face great challenges. Dihydromyricetin (DHM) is a kind of flavone extracted from Ampelopsis grossedentata, a traditional Chinese medicine. DHM can enhance the osteogenic differentiation of human bone marrow mesenchymal stem cells with the potential to promote bone regeneration. Hydrogel can be used as a carrier of DHM to promote bone regeneration due to its unique biochemical characteristics and three-dimensional structure. In this study, oxidized phellinus igniarius polysaccharides (OP) and L-arginine chitosan (CA) are used to develop hydrogel. The pore size and gel strength of the hydrogel can be changed by adjusting the oxidation degree of oxidized phellinus igniarius polysaccharides. The addition of DHM further reduce the pore size of the hydrogel (213 μm), increase the mechanical properties of the hydrogel, and increase the antioxidant and antibacterial activities of the hydrogel. The scavenging rate of DPPH are 72.30 ± 0.33 %, and the inhibition rate of E.coli and S.aureus are 93.12 ± 0.38 % and 94.49 ± 1.57 %, respectively. In addition, PCAD has good adhesion and biocompatibility, and its extract can effectively promote the osteogenic differentiation of MC3T3-E1 cells. Network pharmacology and molecular docking show that the promoting effect of DHM on osteogenesis may be achieved by activating the PI3K/AKT and MAPK signaling pathways. This is confirmed through in vitro cell experiments and in vivo animal experiments.

01 Dec 2024·International Immunopharmacology

Notoginsenoside R1-Protocatechuic aldehyde reduces vascular inflammation and calcification through increasing the release of nitric oxide to inhibit TGFβR1-YAP/TAZ pathway in vascular smooth muscle cells

Article

Author: Zhang, Lei ; Hu, Yuanlong ; Cui, Xinhai ; Zhang, Muxin ; Zhang, Zhiyuan ; Guan, Xiuya ; Sun, Bowen ; Li, Chao ; Li, Yunlun ; Lu, Mengkai ; Lin, Lin ; Hao, Jiaqi

Vascular calcification is a significant factor contributing to the rupture of vulnerable atherosclerotic plaques, ultimately leading to cardiovascular disease. However, no effective treatments are currently available to slow the progression of vascular calcification. Notoginsenoside R1 (R1) and protocatechuic aldehyde (PCAD), primary active components extracted from Panax notoginseng and Salvia miltiorrhiza Burge, have shown potential in mitigating endothelial injury and atherosclerosis. This study investigated the effects of R1-PCAD on nitric oxide (NO) production in endothelial cells (ECs) and its role in counteracting vascular calcification and inflammation. Additionally, it explored the mechanisms underlying these effects. To simulate atherosclerotic calcification, apolipoprotein E-deficient (ApoE^-/-) mice were fed a high-fat diet and given intraperitoneal injections of vitamin D3. Treatment with the R1-PCAD combination improved endothelial function, reduced inflammation in the aorta, and lowered calcium deposition. Mechanistically, R1-PCAD enhanced eNOS-Ser1177 phosphorylation by activating the AMPKα/Akt pathway, which stimulated NO production and eNOS activation in ECs. In an in vitro co-culture model involving vascular smooth muscle cells (VSMCs) and ECs, R1-PCAD similarly reduced inflammation and calcification in VSMCs triggered by β-glycerophosphate, with these effects partially dependent on NO levels and EC functionality. Further investigation revealed that R1-PCAD facilitated NO release from ECs, which subsequently inhibited TGFβR1 activation in VSMCs. This inhibition reduced Smad2/3 activation and nuclear translocation of YAP/TAZ, thereby diminishing inflammation and calcification in VSMCs. These findings suggest that R1-PCAD alleviates vascular inflammation and calcification primarily via the NO-TGFβR1-YAP/TAZ signaling pathway. This study presents a promising new approach for treating vascular calcification by targeting intercellular signaling pathways.

01 Dec 2023·Biomedicine & Pharmacotherapy

Protocatechuic aldehyde increases pericyte coverage and mitigates pericyte damage to enhance the atherosclerotic plaque stability

Article

Author: Liu, Dekun ; Lin, Lin ; Li, Yuan ; Li, Jie ; Yang, Wenqing ; Wu, Jibiao ; Zhang, Lei ; Li, Chao ; Li, Yunlun

Pericyte dysfunction and loss contribute substantially to the destabilization and rupture of atherosclerotic plaques. Protocatechuic aldehyde (PCAD), a natural polyphenol, exerts anti-atherosclerotic effects. However, the effects and mechanisms of this polyphenol on pericyte recruitment, coverage, and pericyte function remain unknown. We here treated apolipoprotein E-deficient mice having high-fat diet-induced atherosclerosis with PCAD. PCAD achieved therapeutic effects similar to rosuvastatin in lowering lipid levels and thus preventing atherosclerosis progression. With PCAD administration, plaque phenotype exhibited higher stability with markedly reduced lesion vulnerability, which is characterized by reduced lipid content and macrophage accumulation, and a consequent increase in collagen deposition. PCAD therapy increased pericyte coverage in the plaques, reduced VEGF-A production, and inhibited intraplaque neovascularization. PCAD promoted pericyte proliferation, adhesion, and migration to mitigate ox-LDL-induced pericyte dysfunction, which thus maintained the capillary network structure and stability. Furthermore, TGFBR1 silencing partially reversed the protective effect exerted by PCAD on human microvascular pericytes. PCAD increased pericyte coverage and impeded ox-LDL-induced damages through TGF-β1/TGFBR1/Smad2/3 signaling. All these novel findings indicated that PCAD increases pericyte coverage and alleviates pericyte damage to improve the stability of atherosclerotic plaques, which is accomplished by regulating TGF-β1/TGFBR1/Smad2/3 signaling in pericytes.

100 Deals associated with PCA-062

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Esophageal Carcinoma	Phase 2	ES	Novartis Pharmaceuticals Corp.	15 Apr 2015
Esophageal Carcinoma	Phase 1	US	Novartis Pharmaceuticals Corp.	15 Apr 2015
Esophageal Carcinoma	Phase 1	SG	Novartis Pharmaceuticals Corp.	15 Apr 2015
Esophageal Carcinoma	Phase 1	JP	Novartis Pharmaceuticals Corp.	15 Apr 2015
Triple Negative Breast Cancer	Phase 1	IT	Novartis Pharmaceuticals Corp.	15 Apr 2015
Triple Negative Breast Cancer	Phase 1	JP	Novartis Pharmaceuticals Corp.	15 Apr 2015
Triple Negative Breast Cancer	Phase 1	ES	Novartis Pharmaceuticals Corp.	15 Apr 2015
Triple Negative Breast Cancer	Phase 1	FR	Novartis Pharmaceuticals Corp.	15 Apr 2015
Esophageal Carcinoma	Discovery	IT	Novartis Pharmaceuticals Corp.	15 Apr 2015
Esophageal Carcinoma	Discovery	FR	Novartis Pharmaceuticals Corp.	15 Apr 2015

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02375958 (Pubmed \| Mol Cancer Ther) Manual	Phase 1	Solid tumor CDH3 Positive	47	PCA-062	(ejujhqpqqs) = thrombocytopenia that was attributed to the known toxicities of the DM1 payload vmessspmlw (dnlwjaursi )	Negative	07 Feb 2022

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

PCA-062

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation