Last update 01 Nov 2024

CD49b

Last update 01 Nov 2024

Basic Info

Synonyms

alpha 2 subunit of VLA-2 receptor, CD49 antigen-like family member B, CD49B

+ [8]

Introduction

Integrin alpha-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. It is responsible for adhesion of platelets and other cells to collagens, modulation of collagen and collagenase gene expression, force generation and organization of newly synthesized extracellular matrix. (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human rotavirus A. (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human echoviruses 1 and 8.

Drugs associated with CD49b

E-7820

Target

CD49b

Mechanism

CD49b inhibitors

Active Org.

Eisai, Inc. [+2]

Originator Org.

Eisai Co., Ltd.

Active Indication

Acute Myeloid Leukemia [+4]

Inactive Indication

Advanced Colorectal Adenocarcinoma [+6]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Vatelizumab

Target

CD49b

Mechanism

CD49b inhibitors [+1]

Active Org.

NMS Group SpA [+1]

Originator Org.

Glenmark Pharmaceuticals Ltd.

Active Indication

Neoplasms

Inactive Indication

Colitis, Ulcerative [+5]

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with CD49b

NCT05024994 / Active, not recruitingPhase 2IIT

A Phase II Clinical Trial of E7820 for Patients With Relapsed/Refractory Myeloid Malignancies With Mutations in Splicing Factor Genes.

The researchers are doing this study to find out whether E7820 is an effective treatment for people with relapsed/refractory myeloid cancers with mutations in splicing factor genes. Participants will have acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or chronic myelomonocytic leukemia (CMML).

Start Date13 Aug 2021

Sponsor / Collaborator

Memorial Sloan Kettering Cancer Center

[+1]

NCT02306811 / TerminatedPhase 2

A Long-Term Follow-up Study Assessing the Safety and Efficacy of Vatelizumab in Multiple Sclerosis (MS) Patients Who Completed Treatment in Study DRI13839

Primary Objective:
To assess the long-term safety of vatelizumab in MS patients
Secondary Objective:
To assess the long-term efficacy of vatelizumab

Start Date01 Feb 2015

Sponsor / Collaborator

Genzyme Corp.

NCT02222948 / TerminatedPhase 2

A Phase 2a/2b Double-Blind, Randomized, Placebo-Controlled Study Assessing Efficacy, Safety, and Dose-Response of Vatelizumab in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)

Primary Objectives:
To assess the efficacy of vatelizumab compared to placebo as measured by a reduction in new contrast-enhancing lesions (CELs) in relapsing remitting multiple sclerosis (RRMS) patients.
To evaluate multiple doses of vatelizumab for a dose-response.
Secondary Objectives:
To evaluate the safety and tolerability of vatelizumab compared to placebo.
To evaluate the pharmacokinetics (PK) of vatelizumab.

Start Date01 Sep 2014

Sponsor / Collaborator

Genzyme Corp.

100 Clinical Results associated with CD49b

100 Translational Medicine associated with CD49b

0 Patents (Medical) associated with CD49b

2,006

Literatures (Medical) associated with CD49b

01 Nov 2024·Life Sciences

NADPH oxidase 1/4 dual inhibitor setanaxib suppresses platelet activation and thrombus formation

Article

Author: Jang, Joara ; Shin, Hye Ji ; Park, Ji Won ; Oh, Eun Bee ; Chang, Tong-Shin ; Yu, Hyunseong

AIMSThe production of reactive oxygen species (ROS) by NADPH oxidase (NOX) is able to induce platelet activation, making NOX a promising target for antiplatelet therapy. In this study, we examined the effects of setanaxib, a dual NOX1/4 inhibitor, on human platelet function and ROS-related signaling pathways.MATERIALS AND METHODSIn collagen-stimulated human platelets, aggregometry, assessment of ROS and Ca²⁺, immunoblotting, ELISA, flow cytometry, platelet adhesion assay, and assessment of mouse arterial thrombosis were performed in this study.KEY FINDINGSSetanaxib inhibited both intracellular and extracellular ROS production in collagen-activated platelets. Additionally, setanaxib significantly inhibited collagen-induced platelet aggregation, P-selectin exposure from α-granule release, and ATP release from dense granules. Setanaxib blocked the specific tyrosine phosphorylation-mediated activation of Syk, LAT, Vav1, and Btk within collagen receptor signaling pathways, leading to reduced activation of PLCγ2, PKC, and Ca²⁺ mobilization. Setanaxib also inhibited collagen-induced activation of integrin αIIbβ3, which is linked to increased cGMP levels and VASP phosphorylation. Furthermore, setanaxib suppressed collagen-induced p38 MAPK activation, resulting in decreased phosphorylation of cytosolic PLA₂ and reduced TXA₂ generation. Setanaxib also inhibited ERK5 activation, affecting the exposure of procoagulant phosphatidylserine. Setanaxib reduced thrombus formation under shear conditions by preventing platelet adhesion to collagen. Finally, in vivo administration of setanaxib in animal models led to the inhibition of arterial thrombosis.SIGNIFICANCEThis study is the first to show that setanaxib suppresses ROS generation, platelet activation, and collagen-induced thrombus formation, suggesting its potential use in treating thrombotic or cardiovascular diseases.

01 Nov 2024·Gene

Landscape of extrachromosomal circular DNAs, transcriptome, and proteome analysis reveals insights into alcoholic liver cirrhosis

Article

Author: Zhou, Junying ; Wang, Yadong ; Zhang, Xin ; Li, Yuanyuan ; Li, Fei ; Liu, Jingwen

Alcoholic liver cirrhosis (ALC) is a result of excessive and chronic alcohol consumption. Because alchol can cause DNA damage, extrachromosomal circular DNA (eccDNA) was investigated in ALC liver due to it can be a result of DNA damage. Considering eccDNA has ability to lead to genomic instability as an enhancer of gene transcription, we utilized Circle-Seq to identify differences in eccDNA profiles and gene expression patterns in liver samples obtained from ALC patients (n = 3) and healthy controls (n = 3) to investigate the role of eccDNA in the development of ALC. The abundance of eccDNA in ALC (mean = 13,349) were higher than the healthy control (mean = 11,557) without significant difference (pvalue = 0.6530). We observed 1,032 eccDNA containing genes showed higher expression in ALC patients compared to healthy controls (p < 0.05, log2FC > 1). Notably, we discovered seven genes that exhibited a significant positive correlation between eccDNA abundance and gene expression levels. These genes include A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2), Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C), Protein TANC1 (TANC1), Integrin alpha-2 (ITGA2), EH domain-containing protein 4 (EHD4), Phosphofurin acidic cluster sorting protein 1 (PACS1), and Neuron navigator 2 (NAV2). Through mass spectrometry proteomics, ITGA2 were found to have significantly higher abbudance in ALC. Integrins are a family of proteins plays key roles in the fibrosis development of liver. Thus, our study opens a new perspective for liver fibrosis development.

01 Oct 2024·International Immunopharmacology

SLC4A4 as a novel biomarker involved in immune system response and lung adenocarcinoma progression

Article

Author: Zhang, Zewei ; Quan, Siyu ; Li, Na ; Liu, Yang ; Gao, Dejun ; Wang, Yuanyuan ; Lian, Shihai ; Li, Yun ; Liu, Jianbo

BACKGROUNDAltered expression and activity of solute carrier family 4 member 4 (SLC4A4) could affect the growth, survival and metastasis of tumor cells. Currently, the role of SLC4A4 in lung adenocarcinoma (LUAD) immunotherapy and prognosis was not entirely clear.METHODSWe analyzed SLC4A4 expression in LUAD tissues and cell lines using quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. The effects of SLC4A4 overexpression on angiogenesis, cell migration, invasion, and epithelial-mesenchymal transition were examined. Public databases helped construct a risk model evaluating SLC4A4's expression on LUAD prognosis and immunotherapy response. Additionally, a xenograft model, flow cytometry, and enzyme-linked immunosorbent assay further explored SLC4A4's role in tumor immune microenvironment infiltration.RESULTSUpregulation of SLC4A4 promoted apoptosis in the LUAD cell line and significantly inhibited the migration and invasive ability of cancer cells (P<0.01). A total of 10 key genes (including SIGLEC6, RHOV, PIR, MOB3B, MIR3135B, LPAR6, KRT8, ITGA2, CPS1, and C6) were screened according to SLC4A4 expression, immune score and stromal score, and a prognostic model with good outcome was constructed (AUC values of which in the training cohort at 1,3, and 5 years reached 0.73, 0.73, and 0.72, respectively). Importantly, we demonstrated that high expression of SLC4A4 was able to increase the proliferation level and cytokine secretion of CD8+ T cells for the purpose of promoting the immune system response to LUAD.CONCLUSIONOur study revealed that SLC4A4 can serve as a prognostic indicator for LUAD, providing new insights into the treatment and diagnosis of LUAD.

News (Medical) associated with CD49b

16 Oct 2023

·www.biospace.com

Incendia Therapeutics Announces Upcoming Presentations at the European Society for Medical Oncology Congress 2023

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Incendia Therapeutics, formerly Parthenon Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), today announced that it will have two poster presentations at the European Society for Medical Oncology (ESMO) Congress 2023, to be held in Madrid, Spain October 20-24, 2023. The company will present data on the expression of discoidin domain receptor 1 (DDR1) mRNA and protein across 20 tumor types and will provide a detailed overview of Incendia’s Phase 1 first-in-human clinical trial for its lead candidate PRTH-101 in patients with advanced solid tumors (NCT05753722). “The tumor microenvironment is dramatically impacted by the over expression of DDR1 and its role in the alignment of collagen fibers, which ultimately prevents immune cells from being able to directly interact with tumors,” said Laura Dillon, Vice President of Translational Medicine and Bioinformatics at Incendia. “These data presented at ESMO further highlight the potential of PRTH-101 as a first-in-class DDR1 inhibitor that may address the unmet need in the numerous cancers with high DDR1 expression.” Presentation Details: Title: High DDR1 mRNA and Protein Expression Across Human Tumor Types Correlate with Epithelial Composition of the Tumor Microenvironment Lead author: Laura Dillon, Ph.D., Vice President, Translational Medicine and Bioinformatics at Incendia Therapeutics Presentation #: 2309P Presentation Time: Saturday, October 21, 12:00 - 1:00 PM CEST (6-7 AM ET) Translational Research (agnostic) Key Highlights: DDR1 is expressed in a high proportion of tumor cells across a range of epithelial tumor types, suggesting potentially broad application of DDR1-targeted therapies. A high proportion of tumor cells (median of 0.76) expressed DDR1 across all epithelial tumor types. DDR1 expression was uniformly low in mesenchymal tumors (median of 9 cells/mm2) compared to epithelial tumors (median of 2803 cells/mm2). Moderate correlation was observed between DDR1 mRNA expression and DDR1+ cell density across tumor types (R=0.48, p<0.0001). In epithelial tumors, both DDR1 mRNA and protein expression were correlated with the percentage of epithelium (R=0.37 and 0.56, respectively; both p<0.0001), with significant variance between tumor types. Title: A Phase 1 First-in-Human Study of PRTH-101, an IgG1 Monoclonal Antibody Targeting DDR1, as a Monotherapy and Combined with Pembrolizumab in Patients with Advanced Solid Malignancies Lead author: Shiraj Sen, M.D., Ph.D., Medical Oncologist and Director of NEXT Oncology Dallas Presentation #: 1079TiP Presentation Time: Monday, October 23, 12:00 – 1:00 PM CEST (6-7 AM ET) (Investigational immunotherapy) Key Highlights: Discoidin domain receptor 1 (DDR1) is a collagen receptor that represents a promising therapeutic target due to its role in excluding lymphocytes from the tumor microenvironment (TME) by aligning collagen fibers. DDR1 expression is high in multiple cancer types and associated with worse survival. PRTH-101 is a humanized IgG1 antibody that binds to the extracellular domain of both membrane-bound and soluble DDR1. In preclinical models, PRTH-101 monotherapy resulted in disruption of aligned collagen fibers in the tumor stroma, increased infiltration of lymphocytes, and tumor growth inhibition. When PRTH-101 is combined with PD-1 inhibition, activated T cell infiltration is increased compared to PRTH-101 alone. This is a Phase 1 first-in-human study that will evaluate intravenous PRTH-101 +/- pembrolizumab in patients with advanced solid tumors. Safety, efficacy, pharmacokinetic, and pharmacodynamic endpoints will be monitored and reported. The first part of the study (Ph1a) seeks to identify the maximum tolerated dose (MTD) or optimal biologic dose (OBD), of PRTH-101 to determine the recommended phase 2 dose (RP2D). The second part (Ph1b) seeks to identify the MTD or OBD of PRTH-101 in combination with pembrolizumab to determine the PRTH-101 combination RP2D. The third part (Ph1c) consists of dose expansion in disease-directed cohorts to assess the anti-tumor efficacy of PRTH-101 monotherapy and/or combination therapy. About PRTH-101 PRTH-101 is a therapeutic antibody that specifically binds to and blocks discoidin domain receptor 1 (DDR1,) a protein expressed on tumor cells that binds collagen to make a physical barrier that prevents immune cells from interacting with and attacking tumor cells. By disabling DDR1, the collagen fibers lose alignment and loosen, creating gaps in the tumor barrier, thus allowing T-cells to enter and attack the tumor. Blockade of DDR1 represents a unique approach to stimulating immune-based antitumor activity, and in preclinical models such blockade shows both single agent anti-tumor activity as well as marked augmentation of immunity enhanced by PD-1 blockade. Tumor types that express high levels of DDR1-associated collagen barriers include colorectal, ovarian, and non-small cell lung cancer. Currently, there are no approved drugs that target DDR1. About Incendia Therapeutics Incendia Therapeutics is discovering and developing a novel class of anti-cancer therapies that reprogram the tumor microenvironment (TME). Recent research has shown that the interplay between tumor cells and their surrounding TME results in the creation of barriers that markedly attenuate the immune system’s ability to attack the tumor. Based on rigorous, groundbreaking research, Incendia is developing a portfolio of drug candidates to treat select patients at the appropriate/ideal stage in disease progression. For more information visit incendia.com and LinkedIn.

Phase 1ImmunotherapyClinical Result

04 Apr 2023

·www.pharmaceutical-technology.com

Adcendo amps up ADC development with €82 million series A extension

Credit: Shutterstock/ nepool On 4 April, the Danish immune-oncology company Adcendo announced the extension of a series A financing round to €82 million ($89.6 million). Adcendo is developing antibody-drug conjugates (ADCs) to treat cancers with few approved therapies. Free Report How is the Biopharmaceutical industry evolving? 2021 was a year of continued innovation and change in the Biopharmaceutical industry. As the COVID-19 pandemic continues to take its toll on businesses worldwide, it’s time to look for new ways to create value, prepare for the future, and remain competitive in the ever-changing landscape. GlobalData’s expansive report examines the business environment and trends that shape the Biopharmaceutical industry. We highlight the most impactful emerging technologies, as well as the industry, regulatory, and macroeconomic factors that influence growth prospects. Access the report to: Benchmark the impact of major themes on the Biopharmaceutical industry. Gain a deeper "on the ground" perspective through exclusive opinions and analysis from industry respondents. Evaluate the effects of COVID-19 on the sector. Download the full report to understand what to expect and how to align your strategies for success. 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Our services are intended for corporate subscribers and you warrant that the email address submitted is your corporate email address. Thank you. Please check your email to download the Report. In April 2021, the company had announced the completion of a €51 million ($62 million) Series A round. Adcendo then went on to raise the additional €31 million ($33.9 million) in the latest extension round, which was led by Pontifax Venture Capital, and existing investors Novo Holdings and Ysios Capital, along with RA Capital Management, HealthCap and Gilde Healthcare. The company is developing a pipeline of ADCs targeting uPARAP (Endo180), an endocytic collagen receptor that is upregulated in several cancers. Adcendo’s ADCs treat cancer by inhibiting uPARAP, which is present on several mesynchymal cancer cells such as fibroblasts, osteoblasts and chondrocytes. When proteins bind to uPARAP, the receptor internalizes and degrades them. Inhibiting uPARAP receptors reduces bone degradation and helps reconstruct tissue in the body. The company studied its first ADC candidate in mice in 2022 , and found sufficient evidence to suggest its possible use for sarcoma treatment. According to GlobalData, Adcendo is at the preclinical stage of developing ADCs for solid tumours, osteosarcoma, glioblastoma (multiforme), malignant mesothelioma, soft tissue sarcoma and acute promyelocytic leukemia. With the latest funds, the company plans to advance its second ADC candidate to the Development Candidate Nomination (DCN) stage in H1 2024. GlobalData is the parent company of Pharmaceutical Technology. In 2022, Adcendo announced a license agreement with Duality Biologics , a Chinese clinical stage biotech also focused on the discovery and development of ADCs. Duality Biologics has a clinical pipeline of five solid tumour drugs, that are in different stages of development from preclinical to Phase II. The company also has two autoimmune drugs, DB-2304 and DB-2306 in preclinical development. Under the terms of the agreement, Adcendo will license Duality’s proprietary DITAC (Duality Immune Toxin Antibody Conjugates) linker platform for its uPARAP-ADC program in mesenchymal cancers. The DITAC platform aims to generate ADCs that can kill antigen low and negative cells efficiently. In a press release accompanying the recen funding news, Adcendo’s CEO Michael Pehl said, “This financing underscores the confidence that our investors have in Adcendo’s capabilities and potential to develop innovative ADC cancer therapies in high unmet medical need cancers”. Free Report How is the Biopharmaceutical industry evolving? 2021 was a year of continued innovation and change in the Biopharmaceutical industry. As the COVID-19 pandemic continues to take its toll on businesses worldwide, it’s time to look for new ways to create value, prepare for the future, and remain competitive in the ever-changing landscape. GlobalData’s expansive report examines the business environment and trends that shape the Biopharmaceutical industry. We highlight the most impactful emerging technologies, as well as the industry, regulatory, and macroeconomic factors that influence growth prospects. Access the report to: Benchmark the impact of major themes on the Biopharmaceutical industry. Gain a deeper "on the ground" perspective through exclusive opinions and analysis from industry respondents. Evaluate the effects of COVID-19 on the sector. Download the full report to understand what to expect and how to align your strategies for success. 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License out/inADCImmunotherapy

05 Jan 2021

·endpts.com

BioXcel scores another win with reformulated Pfizer sedative, this time in an Alzheimer's symptom

Less than six months after reporting positive Phase III results for its lead program in treating agitation related to schizophrenia and bipolar disorder, small AI biotech BioXcel followed up Tuesday with top-line data in an early stage trial for agitation in dementia and Alzheimer’s disease. The experimental drug, known as BXCL501, met its primary and secondary endpoints in the higher evaluable dose of a 54-patient Phase Ib/II trial, BioXcel announced, inducing a statistically significant calming effect compared to placebo with no severe or serious side effects. With the data in hand, BioXcel plans to meet with the FDA sometime in the first half of 2021 before launching a late-stage study sometime afterwards. BioXcel $BTAI shares ticked up by as much as 10% in pre-market trading Tuesday, but after the opening bell were down about 7%. BXCL501 is a reformulation of Pfizer’s 21-year-old sedation drug Precedex. BioXcel created a dissolving film-based, sublingual version of the drug — think Listerine strips, but placed under the tongue — that patients administered themselves. It essentially produces a calming effect without knocking a patient out and activates the alpha-2 receptor, the pathway through which norepinephrine, among other neuro-chemicals, travels. Tuesday’s data come from a double-blinded and randomized study conducted entirely within assisted living facilities. Patients in the drug cohorts received either a 30 μg, 60 μg or 90 μg dose, though BioXcel did not measure efficacy or safety in the 90 μg arm due to higher exposure levels. Sixteen patients received the 30-μg dose, 20 took the 60-μg dose, four began the 90-μg dose level and 14 were randomized to the placebo group. It’s the 60 μg level where BXCL501 differentiated itself from placebo at a significant level. The program hit on all three scales used to measure change in agitation from baseline, the PEC, PAS, and Mod-CMAI. For the PEC, the p-value was p=0.0011, while the other two p-values registered at p<0.0001. The candidate also showed a rapid onset, BioXcel said, hitting statistical significance compared with placebo in the PEC and PAS just one hour after patients took the film strips, with the company noting it didn’t measure Mod-CMAI after this time period. Calming effects at this dosing level remained at statistically significant levels through eight hours. BXCL501’s 30-μg dose did not hit statistical significance in any of the three scales, clocking in at p=0.0813 for PEC, p=0.0961 for PAS and p=0.0591 in the Mod-CMAI. The most common side effect was somnolence, or drowsiness. Half of the 16 patients in the 30-μg cohort self-reported mild drowsiness, while 11 of 20 individuals in the 60-μg cohort did so. There was one case of moderate drowsiness in the 60-μg group as well. In addition, there were two cases of hypotension in the 60-μg cohort, one mild and one moderate, as well as one case of mild dizziness. Jefferies analyst Chris Howerton took a positive view of the data, writing that the 60-μg dose appears to “check all the boxes.” The safety at this dose level looked “clean,” though Howerton noted because Precedex is known to be more potent in elderly patients, he wouldn’t be surprised if BioXcel also looked at a 45-μg dose in their pivotal trial. The issue of a 45-μg dose also came up in a conference call BioXcel held Tuesday morning with investors. CEO Vimal Mehta said that although BioXcel will likely prioritize 60 μg for the Phase III given Tuesday’s top-line results, they aren’t ruling out also testing 45 μg. Mehta also said on the call that he doesn’t anticipate much disruption in Phase III enrollment related to the ongoing Covid-19 pandemic. BioXcel is one in a slate of biotechs that has raised millions in recent years on the promise of using artificial intelligence to speed the drug development process. The company filed for a $69 million IPO in 2018 less than a year after being founded, and has aimed to use its tech to find compounds validated to some degree by other companies and repurpose them. Back in July, BioXcel reported that in two nearly 400-person Phase III trials for bipolar disorder and schizophrenia, the lead drug effectively calmed patients’ agitation.

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