Effects of Combination Medical Therapy Followed by Balloon Pulmonary Angioplasty on Right Ventricular-PA Coupling and Hemodynamics in Chronic Thromboembolic Pulmonary Hypertension

The main goal of this study is to determine the effects of combination medical therapy (Riociguat and Macitentan) and balloon pulmonary angioplasty (BPA) on hemodynamics and right ventricular (RV) function (including advanced assessments of RV-pulmonary artery (PA) coupling from invasive hemodynamics) in participants with inoperable or post-PTE residual CTEPH.

开始日期2024-09-30

申办/合作机构

Duke University

[+1]

100 项与 ETB x ETA 相关的临床结果

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100 项与 ETB x ETA 相关的转化医学

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0 项与 ETB x ETA 相关的专利（医药）

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项与 ETB x ETA 相关的文献（医药）

2024-12-01·Molecular Biology Reports

Epidemiological characterization of clinical isolates of meticillin resistant Staphylococcus aureus through multilocus sequence typing and staphylococcal cassette chromosome mec typing in Northwest Iran

Article

作者: Memar, Mohammad Yousef ; Ghotaslou, Reza ; Sheykhsaran, Elham ; Sefidan, Fatemeh Yeganeh ; Baghi, Hossein Bannazadeh ; Sharifi, Yaeghob ; Laghousi, Delara ; Sadeghi, Javid ; Abbasi, Amin

BACKGROUNDMethicillin-resistant Staphylococcus aureus (MRSA), is considered a potential and aggressive nosocomial pathogen. It accounts for 50% of S. aureus isolates in tertiary hospitals in Iran, however, there is no sufficient evolutionary and epidemiological investigation about this medically important bacterium. We aimed to study the lineage and evolution of MRSA in Northwest Iran during 2021-2022 based on the obtained phenotypic and genotypic characteristics.MATERIALS AND METHODSSeventy-two non-duplicate MRSA isolates were collected from 3 referral hospitals in Tabriz, Ardebil, and Urmia cities. The antimicrobial susceptibility patterns were determined by disk diffusion test and micro broth dilution methods. Thereafter 4 virulence genes (eta, etb, pvl, tst) and 5 types of staphylococcal cassette chromosome mec (SCCmec) were detected by PCR. In the final step, representative isolates were selected to be studied by Multilocus sequence typing (MLST).RESULTSThe highest resistance was observed to erythromycin and clindamycin at a rate of 76.4%, followed by ciprofloxacin (61.1%), gentamicin (54.2%), rifampin (38.9%), and co-trimoxazole (27.8%). All isolates were susceptible to vancomycin. The virulence genes of etb, pvl, tst, and eta were detected in 50%, 29.2%, 21.8%, and 13.9% of isolates, respectively. SCCmec types III and I were the most prevalent types, followed by types IV, II, and V. MLST analysis revealed 6 sequence types: ST6854, ST5282, ST127, ST7804, ST1607, and ST7784. Two MLST-based clonal complexes (CC8, and CC97) were identified as well.CONCLUSIONThe ST numbers were non-repetitive. CC8 as a pandemic clone and an individual lineage and clinically significant clade was reported as the most prevalent clonal complex. It is essential periodic evaluations of antibiotic susceptibility patterns and study the evolutionary characteristics of medical-challenging microorganisms in particular MRSA to effectively treat and restrict the outbreaks.

2024-11-06·Clinical Science

Complex regulation of tau phosphorylation by the endothelin system in brain microvascular endothelial cells (BMVECs): link to barrier function

Article

作者: Ergul, Adviye ; Jamil, Sarah ; Abdul, Yasir ; Albayram, Onder ; Edwards, Jazlyn ; Karakaya, Eda

AbstractEndothelin-1 (ET-1), the most potent vasoconstrictor identified to date, contributes to cerebrovascular dysfunction. ET-1 levels in postmortem brain specimens from individuals diagnosed with Alzheimer’s disease (AD) and related dementias (ADRD) were shown to be related to cerebral hypoxia and disease severity. ET-1-mediated vascular dysfunction and ensuing cognitive deficits have also been reported in experimental models of AD and ADRD. Moreover, studies also showed that ET-1 secreted from brain microvascular endothelial cells (BMVECs) can affect neurovascular unit integrity in an autocrine and paracrine manner. Vascular contributions to cognitive impairment and dementia (VCID) is a leading ADRD cause known to be free of neuronal tau pathology, a hallmark of AD. However, a recent study reported cytotoxic hyperphosphorylated tau (p-tau) accumulation, which fails to bind or stabilize microtubules in BMVECs in VCID. Thus, the study aimed to determine the impact of ET-1 on tau pathology, microtubule organization, and barrier function in BMVECs. Cells were stimulated with 1 μM ET-1 for 24 h in the presence/absence of ETA (BQ123; 20 μM) or ETB (BQ788; 20 μM) receptor antagonists. Cell lysates were assayed for an array of phosphorylation site-specific antibodies and microtubule organization/stabilization markers. ET-1 stimulation increased p-tau Thr231 but decreased p-tau Ser199, Ser262, Ser396, and Ser214 levels only in the presence of ETA or ETB antagonism. ET-1 also impaired barrier function in the presence of ETA antagonism. These novel findings suggest that (1) dysregulation of endothelial tau phosphorylation may contribute to cerebral microvascular dysfunction and (2) the ET system may be an early intervention target to prevent hyperphosphorylated tau-mediated disruption of BMVEC barrier function.

2024-11-01·Biochemical and Biophysical Research Communications

Crystal structure of exfoliative toxin D from Staphylococcus aureus

Article

作者: Nishikawa, Atsushi ; Nishifuji, Koji ; Ragab, Rokaia F ; Guo, Xu ; Tonozuka, Takashi ; Sato, Shu ; Elfadadny, Ahmed ; Kozono, Takuma ; Ragab, Rokaia F.

Staphylococcus aureus exfoliative toxins (ETs) are serine proteases responsible for staphylococcal scalded skin syndrome. Four ETs, ETA, ETB, ETD, and ETE, have been identified, all of which cleave desmoglein-1. This study presents the crystal structure of ETD at 1.75 Å resolution. The protein exhibits a structure composed of two β-barrels and two α-helices as described in previous studies of ETs. A predicted model of ETD in complex with Ile380-Glu381-Gly382-Pro383 (IEGP), a segment of human desmoglein-1 (hDsg1), was constructed. Glu381 of hDsg1 was predicted to interact with as many as six amino acid residues in ETD, whereas two amino acid residues in ETD primarily constituted subsite S1', and a space near subsite S1' was noted. It is likely that polypeptide chains located near the IEGP segment in the predicted structure of hDsg1 bind to this space. The structure of loop D, which was predicted to participate in subsite S2', in ETD was markedly different from those in other ETs.

项与 ETB x ETA 相关的新闻（医药）

2024-10-14

·PRNewswire

BioCity will present the late-breaking clinical trial data of its ETA selective antagonist SC0062 at the American Society of Nephrology (ASN) 2024 with simultaneous publication of the trial data in the Journal of the American Society of Nephrology (JASN)

SHANGHAI, Oct. 14, 2024 /PRNewswire/ -- BioCity Biopharma announced that a late-breaking clinical trial abstract of its endothelin receptor type A (ETA) selective antagonist SC0062 has been selected for oral presentation at ASN Kidney Week 2024 which will take place from October 23 to 27 in San Diego, USA. The outstanding clinical data will be published simultaneously in JASN, the leading kidney journal in the world. The abstract titled "SC0062, a New Selective Endothelin Receptor Type A Antagonist in lgA Nephropathy" will be presented by Dr. Hiddo Lambers Heerspink from the University Medical Center Groningen. The details of presentation as below: Oral Abstract Session Session Title：Late-Breaking Science Orals -2 Session Date/Time：October 26,2024 from 4:30PM to 6:00 PM Session Room: Room 6C (Convention Center) Abstract Publication #：SA-OR103 Presentation Time: 5:30 PM to 5:40 PM SC0062 has been granted the Breakthrough Therapy Designation (BTD) by the Chinese regulatory agency National Medical Products Administration (NMPA) for the treatment of IgA Nephropathy (IgAN) with proteinuria. The randomized double-blind, placebo-controlled Phase 2 trial of SC0062 (2-SUCCEED) demonstrated a clinically meaningful and statistically significant reduction in proteinuria in IgAN with a clear dose-response relationship and good safety profile. The 2-SUCCEED study is ongoing for the diabetic kidney disease (DKD) cohort with results are expected in the near future. Currently, BioCity is planning Phase 3 clinical trials of SC0062 in China and worldwide intended for regulatory approval of SC0062 for IgAN as well as for the chronic kidney disease (CKD). About SC0062 SC0062 is a novel and highly unique ETA antagonist due to its high selectivity for ETA over endothelin receptor B (ETB). The high ETA selectivity suggests that it has a greater potential than non-selective ET antagonists for reducing progression of CKD while avoiding the safety risks associated with other nonselective molecules in the same class. Preclinical studies have shown that SC0062 improves pathological scores in models of acute kidney injury and CKD. In the completed Phase I study, SC0062 demonstrated a favorable safety profile, good tolerability, and predictable pharmacokinetic characteristics. Fluid retention, an adverse event associated with non-selective ET antagonists due to undesirable ETB blockade, was not observed in the phase 1 trial in healthy volunteers nor in the IgAN cohort of the Phase 2 study. SC0062 is potentially a best-in-class ETA selective antagonist. The ongoing Phase 2 clinical study is designed to evaluate the efficacy and safety of SC0062 in patients with CKD with proteinuria. It is a multi-center, randomized, double-blind, placebo-controlled study with two parallel cohorts (IgAN and DKD). The 2-SUCCEED study has fully enrolled all subjects in two cohorts. The primary endpoint in the IgAN cohort was met and based on this result SC0062 has granted BTD from NMPA and will be published in JASN, whereas the study is ongoing in the DKD cohort, and the results are expected in Q4 of this year. About BioCity Founded in December 2017, BioCity is a clinical-stage biopharmaceutical company committed to developing novel and highly differentiated, modality-independent therapeutics for cancer and autoimmune disorders including CKD. BioCity has established a pipeline of more than 10 innovative drug candidates, including small molecules, monoclonal and bispecific antibodies, and antibody-drug conjugates (ADC). Currently, BioCity's SC0062, a highly selective ETA antagonist, is in Phase 2 clinical development for CKD and a global Phase 3 registration trial is being planned. In addition, BioCity has five core oncology assets in Phase 1/2 clinical development, including first-in-class CDH3-targeting ADC and GPC3-targeting ADCs, WEE1 and ATR inhibitors targeting the DNA damage response (DDR) pathway, and a monoclonal antibody targeting TIM-3 in collaboration with AstraZeneca. For more information, please visit Or LinkedIn BioCity Biopharma Contact: [email protected] [email protected] SOURCE BioCity Biopharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床2期临床结果临床1期突破性疗法临床3期

2024-10-10

·BiG生物创新社

2024年FDA批准新药汇总

作者｜momo 截止目前，FDA已经批准35款新药上市，其中多款药物具有里程碑意义。 01 2024年FDA已批准药物 1.1.Zelsuvmi (berdazimer) 适应症：局部传染性软疣批准日期：2024年1月5日企业：Novan Inc. 1.2.Exblifep (cefepime and enmetazobactam) 适应症：尿路感染靶点：LACTB、PBP 批准日期：2024年2月22日企业：Orchid Chemicals & Pharmaceuticals Ltd. 1.3.Letybo (letibotulinumtoxin a-WLBG) 适应症：中度至重度眉间纹的外观改善靶点：BoNT/A 批准日期：2024年2月29日企业：Hugel Inc. 1.4.Tevimbra (tislelizumab-JSGR) 适应症：不可切除、局部晚期或转移性食管鳞状细胞癌靶点：PD-1 批准日期：2024年3月13日企业：百济神州 1.5.Rezdiffra (resmetirom) 适应症：中晚期非肝硬化性非酒精性脂肪性肝炎靶点：THR-β 批准日期：2024年3月14日企业：罗氏 1.6.Tryvio 适应症：高血压靶点：ET-A、ET-B 批准日期：2024年3月19日企业：Idorsia. 1.7.Duvyzat 适应症：杜氏肌营养不良症靶点：HDAC 批准日期：2024年3月21日企业：Italfarmaco Spa. 1.8.Winrevair (sotatercept-CSRK) 适应症：肺动脉高压靶点：INHBA 批准日期：2024年3月26日企业：Acceleron Pharma Inc. 1.9.Vafseo 适应症：成人慢性肾脏疾病引起的贫血靶点：HIF 批准日期：2024年3月27日企业：宝洁 1.10.Voydeya 适应症：阵发性夜间血红蛋白尿治疗血管外溶血靶点：CFD 批准日期：2024年3月29日企业：Achillion Pharmaceuticals Inc. 1.11.Zevtera (ceftobiprole medocaril sodium) 适应症：血液感染、细菌性皮肤和相关组织感染、社区获得性细菌性肺炎靶点：PBP 批准日期：2024年4月3日企业：Roche 1.12.Lumisight 适应症：乳腺癌荧光成像批准日期：2024年4月17日企业：Lumicell Inc., 杜克大学 1.13.Anktiva (nogapendekin alfa inbakicept-pmln) 适应症：膀胱癌靶点：IL-15R 批准日期：2024年4月22日企业：Altor Bioscience Corp. 1.14.Ojemda (tovorafenib) 适应症：复发或难治性儿童低级别胶质瘤靶点:RAF 批准日期：2024年4月23日企业：Viracta Therapeutics Inc. 1.15.Xolremdi (mavorixafor) 适应症：治疗12岁及以上患有WHIM综合征的患者靶点：CXCR4 批准日期：2024年4月26日企业：赛诺菲 1.16.Imdelltra (tarlatamab-dlle) 适应症：广泛期小细胞肺癌靶点：CD3E、DLL3 批准日期：2024年5月16日企业：Amgen Inc. 1.17.Rytelo (imetelstat) 适应症：低危骨髓增生异常综合征伴输血依赖性贫血靶点：Telomerase 批准日期：2024年6月6日企业：Geron Corp. 1.18.Iqirvo (elafibranor) 适应症：原发性胆汁性胆管炎靶点：PPARɑ/γ 批准日期：2024年6月10日企业：Genfit SA 1.19.Sofdra (sofpironium) 适应症：原发性腋窝多汗症靶点：AChR 批准日期：2024年6月18日企业：Bodor Laboratories Inc. 1.20.Piasky (crovalimab-akkz) 适应症：阵发性睡眠性血红蛋白尿症靶点：C5 批准日期：2024年6月20日企业：Sino-Foreign Pharmaceutical Co., Ltd. 1.21.Ohtuvayre（Ensifentrine）适应症：治疗慢性阻塞性肺病靶点：PDE3/4 批准日期：2024年6月26日企业：Verona Pharma. 1.22.Kisunla（Donanemab-azbt）适应症：阿尔兹海默病靶点：pGlu3Aβ 批准日期：2024年7月2日企业：lilly 1.23.Leqselvi（Deuruxolitinib）适应症：严重斑秃靶点：JAK 批准日期：2024年7月25日企业：Sun Pharmaceuticals 1.24.Voranigo（vorasidenib）适应症：IDH1或IDH2易感突变的2级星形细胞瘤或少突胶质细胞瘤。靶点：IDH1、IDH2 批准日期：2024年8月6日企业：Servier Pharmaceuticals 1.25.Yorvipath（palopegteriparatide）适应症：甲状旁腺功能亢进批准日期：2024年8月9日企业：ascendis Pharma. 1.26.Nemluvio（nemolizumab-ilto）适应症：结节性痒疹靶点:IL-31 批准日期：2024年8月12日企业：Galderma Pharma. 1.27. Livdelzi（seladelpar）适应症：原发性胆汁性胆管炎靶点：PPAR-δ 批准日期：2024年8月14日企业：Gilead Sciences 1.28.Niktimvo（axatilimab-csfr）适应症：慢性移植物抗宿主病靶点CSF-1R 批准日期：2024年8月14日企业：Incyte/Syndax制药 1.29.Lazcluze（lazertinib）适应症：非小细胞肺癌靶点：EGFRm 批准日期：2024年8月19日企业：强生 1.30.Ebglyss（lebrikizumab-lbkz）适应症：中度至重度特应性皮炎靶点：IL-13 批准日期：2024年9月13日企业：lilly 1.31.Miplyffa（arimoclomol）适应症：C型尼曼-匹克病靶点：HSP 批准日期：2024年9月20日企业：Zevra Therapeutics 1.32.Aqneursa （levacetylleucine）适应症：儿童和成人C型尼曼匹克病批准日期：2024年9月24日企业：IntraBio. 1.33.Cobenfy（xanomeline and trospium chloride）适应症：成人精神分裂症靶点：M1-和M4-选择性毒蕈碱受体批准日期：2024年9月26日企业：百时美施贵宝 1.34.Flyrcado（flurpiridaz F 18）适应症：评估心脏血流阻塞（心肌缺血）和心脏病发作（心肌梗塞）批准日期：2024年9月27日企业：GE HealthCare 1.35.Tevimbra（Tislelizumab）适应症：不可切除或转移性食管鳞状细胞癌靶点：PD-1 批准日期：2024年10月4日企业：百济神州 02 2024年FDA批准的突出药物 Voranigo（vorasidenib）这种双重IDH1/IDH2抑制剂处理导致癌细胞代谢变化的突变。它被批准用于2级星形细胞瘤或少突胶质细胞瘤，这是一种生长缓慢的脑肿瘤，具有显著的风险。这是一个突破，因为它直接针对驱动肿瘤生长的突变，提供了一种更有效的治疗选择，可以延缓疾病进展，减少对辐射等侵入性治疗的依赖。 Niktimvo（Axatilimab）是一种CSF-1R单克隆抗体，通过限制巨噬细胞活性来治疗cGVHD，巨噬细胞在免疫应答中起着至关重要的作用。这种疗法对患有cGVHD的患者至关重要，这是干细胞移植后的一种严重并发症，通常对现有治疗无效。它提供了一种更有针对性的策略来改善患者的生活质量。 Cobenfy作为Xanomeline和Trospium Chloride这种联合治疗方法，通过调节毒蕈碱受体，为治疗精神分裂症带来了新的途径。通过平衡大脑中的神经递质活动，它解决了这种疾病的阳性和阴性症状，这使得它对那些用其他药物都没有成功的患者特别有价值。它的双重机制提供了更全面的症状管理，改善了那些受这种具有挑战性的精神健康状况影响的结果。 Rezdiffra（resmetirom）是一款甲状腺激素受体（THR）-β口服选择性激动剂，THR-β在肝脏中高度表达，能够调节脂代谢，降低LDL-C、甘油三酯和致动脉粥样硬化性脂蛋白。此外，THR-β还能通过促进脂肪酸的分解和刺激线粒体的生物发生来减少脂肪毒性并改善肝功能，从而减少肝脏脂肪。Rezdiffra用于治疗患有中重度肝纤维化（F2至F3期）的非肝硬化非酒精性脂肪性肝炎（NASH）患者，成为FDA批准的首款NASH疗法，具有里程碑意义。 Anktiva是一款IL-15超级激动剂。IL-15通过影响自然杀伤（NK）细胞和免疫T细胞的发育、维持和功能，在免疫系统中发挥着至关重要的作用。Anktiva由与IL-15受体α/IgG1 Fc融合蛋白结合的IL-15突变体（IL-15N72D）组成。它与βγ T细胞受体结合，直接特异性刺激CD8阳性T细胞和NK细胞，同时避免刺激调节性T细胞（Treg）。与天然、非复合IL-15相比，Anktiva在患者体内具有更优的药代动力学特性，且能在淋巴组织中存在更长时间，表现出增强的抗肿瘤活性。Anktiva在2019年获FDA授予突破性疗法认定，用于与BCG联合治疗此前对BCG应答不佳的非肌层浸润性原位膀胱癌患者。参考资料 [1]Novel Drug Approvals for 2024 | FDA [2]百济神州官网 BiG近期会议 10月26日，第三届生物计算大会保留栏目-第二届吐槽大会即将再度来袭！本届吐槽大会将围绕投融资、行业心态、年轻人，及AI等热门话题展开策划，通过移幕换景，大咖带新秀，让更多80-00后的行业亲历者来到聚光灯下，邀与会嘉宾一同探讨AI+Biomed的融合之道！共建Biomedical创新生态圈！如何加入BiG会员？

上市批准

2024-09-30

·Pharmaceutical Technology

J&J clinches EC approval for first single-pill PAH combo

The European Commission has approved Johnson and Johnson’s Yuvanci for pulmonary arterial hypertension, offering the first single-pill treatment option to European patients. Credit: andreswd via Getty Images. The European Commission (EC) has approved Johnson and Johnson’s Yuvanci (macitentan + tadalafil) for the treatment of pulmonary arterial hypertension (PAH). The approval marks Yuvanci as the only single-tablet combination therapy available for patients with PAH. PAH is a rare, progressive disorder in which patients have high blood pressure in the pulmonary arteries for no apparent reason. Current treatment for PAH involves first-line dual combination therapy with macitentan and tadalafil for patients without cardiopulmonary comorbidities. This currently consists of a multi-pill regimen. “This can deeply impact their [PAH patients’] daily lives as they might struggle to maintain adherence to their treatment regimen,” said Dr. Tamara Werner-Kiechle, the Europe, Middle East, and Africa (EMEA) therapeutic area lead for neuroscience and cardiopulmonary drugs at Johnson & Johnson Innovative Medicine in a 30 September press release. Johnson and Johnson has developed the Yuvanci as a substitution therapy for the long-term treatment of PAH in adults of the World Health Organization’s (WHO) Functional Class (FC) II to III. This includes patients with PAH that causes a slight limitation in physical activity, yet they are still comfortable at rest, and “patients with marked limitations to physical activity”, as per WHO. Patients will need to have already been treated with a two-pill combination of macitentan and tadalafil to be eligible for Yuvanci. Johnson and Johnson currently markets macitenan monotherapy under the brand name Opsumit, whilst Eli Lilly sells tadalafil as Cialis for PAH. The approval is based on data from the Phase III A DUE study (NCT03904693) , which also led to a positive recommendation for Yuvanci’s approval by the European Medicines Agency’s (EMA) Committee for Human Medicinal Products in July. The pharmaceutical giant presented data from the Phase III A DUE clinical study at the American College of Cardiology’s 72nd Annual Scientific Session. In the double-blind study, Yuvanci-treated patients showed significant improvements in the co-primary endpoints of pulmonary vascular resistance (PVR) and pulmonary haemodynamic improvement. Patients who took the combination therapy demonstrated a 44% decrease in PVR compared to a 22% decrease in the Adcirca monotherapy group. See Also: Almac Group North American Headquarters Expansion, Pennsylvania, USA LOTTE BIOLOGICS’ East Syracuse Pharmaceutical Manufacturing Facility, US Opsumit is an endothelin receptor antagonist that treats PAH by inhibiting pathways related to vasoconstriction, fibrosis and proliferation. Meanwhile, Cialis is a phosphodiesterase type-5 inhibitor that treats the disorder by increasing cGMP, leading to a relaxation of the pulmonary vascular smooth muscle cell and vasodilation of the pulmonary vascular bed. Johnson and Johnson submitted a new drug application to the US Food and Drug Administration (FDA) for Yuvanci in May 2023, receiving an approval for its submission in March 2024.