This is a phase I dose-escalation study of oral PCLX-001, conducted in a multicenter, non-randomized, open-label, non-controlled design. The study is comprised of two parts: Part A (single-agent dose escalation) and Part B (single-agent expansion cohorts).

开始日期2021-09-14

申办/合作机构

Pacylex Pharmaceuticals, Inc.

100 项与 Zelenirstat 相关的临床结果

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100 项与 Zelenirstat 相关的转化医学

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100 项与 Zelenirstat 相关的专利（医药）

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145

项与 Zelenirstat 相关的文献（医药）

2024-02-01·Neuroscience

Post-stress Social Interaction and 3-Cyano-N-(1,3-Diphenyl-1H-Pyrazol-5-yl) Benzamide Treatment Attenuate Depressive-like Behavior Induced by Repeated Social Defeat Stress

Article

作者: Wang, Ying ; Zhang, Liangui ; Chen, Fujun ; Li, Shengtian ; Otani, Satoru

Persistent stress increases the probability for developing depression significantly thereafter. Repeated social defeat stress is a widely used model to investigate depressive-like behavior in preclinical models. Hence, the repeated social defeat stress model provided an ideal animal model, through which the hypotheses of prevention and treatment can be investigated. We have successfully induced depressive-like behavior for male C57BL/6J mice with this model. Here, we reported that certain level of during-stress social interactions with single female or multiple male peer(s) exerted a positive role in preventing the development of depressive-like behavior induced by repeated social defeat stress. Our data suggested that the stress-susceptible mice may benefit from positive social interaction, which reduces the chance for depressive-like behavior development. Since numerous studies indicate that the metabotropic glutamate receptor 5 (mGluR5) plays an important role in various cognitive functions, we further investigate the treatment effect of 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) on the depressive-like behavior induced by repeated social defeat stress. Most importantly, robust anti-depressant effects have been achieved through modulating the mGluR5 function. We found that single oral dose administration of CDPPB (20 mg/kg), to some extent, alleviated the social avoidance behaviors for the stress-susceptible mice. Our data implies that the CDPPB, a positive allosteric modulator of mGluR5, is a promising anti-depressant candidate with limited side effect.

2023-11-01·Chemistry & Biodiversity

Targeting AKT2 in MDA‐MB‐231 Cells by Pyrazole Hybrids: Structural, Biological and Molecular Docking Studies

Article

作者: Markad, Datta ; Pol, Rushikesh ; Nimal, Snehal K ; Kate, Anup N ; Gaikwad, Sanjay S ; Jadhao, Amardeep R ; Patil, Limbraj R ; Jadhav, Umesh ; Gacche, Rajesh N ; Chikate, Rajeev C

AbstractPyrazolic hybrids appended with naphthalene, p‐chlorobenzene, o‐phenol and toluene have been synthesized using Claisen Schmidt condensation reaction of 1‐benzyl‐3,5‐dimethyl‐1H‐pyrazole‐4‐carbaldehyde. All compounds were characterized by various spectroscopic techniques. Compound (E)‐3‐(1‐benzyl‐3,5‐dimethyl‐1H‐pyrazol‐4‐yl)‐1‐(4‐chlorophenyl)prop‐2‐en‐1‐one crystallizes in monoclinic crystal system with C2/c space group. These synthesized compounds were tested for cytotoxic activity and among these compounds 4b and 5a shows prominent cytotoxic activity against triple‐negative breast cancer (TNBC) cells MDA‐MB‐231 with IC50 values 47.72 μM and 24.25 μM, respectively. Distinguishing morphological changes were noticed in MDA‐MB‐231 cells treated with pyrazole hybrids contributing to apoptosis action. To get more insight into cytotoxic activity, in silico molecular docking of these compounds were performed and the results suggested that (E)‐3‐(1‐benzyl‐3,5‐dimethyl‐1H‐pyrazol‐4‐yl)‐1‐(p‐tolyl)prop‐2‐en‐1‐one and 1‐(1′‐benzyl‐5‐(4‐chlorophenyl)‐3′,5′‐dimethyl‐3,4‐dihydro‐1′H,2H‐[3,4′‐bipyrazol]‐2‐yl)ethan‐1‐one binds to the prominent domain of Akt2 indicating their potential ability as Akt2 inhibitor. Moreover, from in silico ADME studies clearly demonstrated that these compounds may be regarded as a drug candidate for sub‐lingual absorption based on log p values (2.157–4.924). These compounds also show promising antitubercular activity. The overall results suggest that pyrazolic hybrids with substitution at less sterically hindered positions have appealing potent cytotoxic activity and antituberculosis activity due to which they may act as multidrug candidate.

2023-10-01·European Journal of Medicinal Chemistry

Synthesis, biological screening and in silico studies of new N-phenyl-4-(1,3-diaryl-1H-pyrazol-4-yl)thiazol-2-amine derivatives as potential antifungal and antitubercular agents

Article

作者: Chavan, Abhijit ; Pissurlenkar, Raghuvir R S ; Maliwal, Deepika ; Nandurkar, Yogesh ; Katade, Sushma ; Mhaske, Pravin C ; Bhoye, Manish R

A new series of N-aryl-4-(1,3-diaryl-1H-pyrazol-4-yl)thiazol-2-amine, (8a-x) have been synthesized by a cyclo-condensation reaction of 2-bromo-1-(1,3-diphenyl-1H-pyrazol-4-yl)ethanone (6a-f) with N-aryl thiourea, (7a-d). The structure of newly synthesized N-aryl-4-(1,3-diaryl-1H-pyrazol-4-yl)thiazol-2-amine, (8a-x) derivatives was analyzed by ¹H NMR, ¹³C NMR and Mass spectral analysis. The compounds 8a-x were screened for in vitro antimicrobial activity against Escherichia coli, Proteus mirabilis, Bacillus subtilis, Staphylococcus aureus, Candida albicans and Aspergillus niger. and antitubercular activity against M. tuberculosis H37Rv strain. Among the twenty-four pyrazolyl-thiazole derivatives, six compounds 8a, 8b, 8j, 8n, 8o and 8s showed good activity against S. aureus. Against A. niger, all synthesized derivatives showed good antifungal activity. Fifteen pyrazolyl-thiazole derivatives 8a, 8f, 8g, 8h, 8j, 8k, 8n, 8o, 8p, 8q, 8r, 8s, 8t, 8w and 8x showed good antitubercular activity with MIC 1.80-7.34 μM (0.8-3.12 μg/mL), these derivatives have showed more activity than the drugs isoniazid and ethambutol. The active compounds were further screened for cytotoxicity activity against the mouse embryonic fibroblast cells (3t3l1) cell lines at 12.5 and 25 μg/mL concentrations and found less or non-cytotoxicity. To know the plausible mode of action, the synthesized pyrazolyl-thiazole derivatives were studied for pharmacokinetics, toxicity profiles and binding interactions along with an in-depth analysis of structural dynamics and integrity using prolonged molecular dynamics (MD) simulation. The compounds have shown significant docking scores in the range of -7.98 to -5.52 and -9.44 to -7.2 kcal/mol with the M. tuberculosis enoyl reductase (M. tb. InhA) and C. albicans sterol 14-α demethylase (C. ab. CYP51), respectively. Thus, the significant antifungal and antitubercular activity of N-aryl-4-(1,3-diaryl-1H-pyrazol-4-yl)thiazol-2-amine, (8a-x) derivatives incited that, these scaffolds could assist in the development of lead compounds to treat fungal and antitubercular infections.

项与 Zelenirstat 相关的新闻（医药）

2024-04-22

·Outsourcing Pharma

Pacylex Pharma's phase one trial: Zelenirstat safety in heavily pre-treated patients

The presentation will be delivered by CEO Michael Weickert at the World Orphan Drug Congress USA 2024 which starts tomorrow (April 23). “The phase 1 results mark a significant milestone in our journey towards addressing critical unmet needs in cancer treatment,” says Dr. Michael Weickert, CEO of Pacylex Pharmaceuticals. “The data underscores the potential of zelenirstat as a promising therapeutic option for patients battling hematologic cancers and solid tumors.” Solid tumors and lymphomas The phase 1 study, focused on dose escalation safety and tolerability, involved 29 heavily pre-treated patients with solid tumors and lymphomas, each having a median history of four prior lines of drug therapy. According to the findings, treatment-related adverse events were observed in a minority of patients, primarily consisting of mild to moderate gastrointestinal side effects. The establishment of a recommended phase 2 dose (RP2D) for expansion studies was a significant outcome of the trial. “Zelenirstat demonstrated promising efficacy outcomes, particularly in solid tumor patients receiving the RP2D,” says Weickert. “This includes prolonged progression-free and overall survival rates, along with instances of prolonged Stable Disease, further highlighting its potential as a therapeutic breakthrough.” Acute Myeloid Leukemia (AML) cells Furthermore, preclinical studies, encompassing in vitro, ex vivo, and in vivo animal trials, have shown that NMT inhibition disrupts prosurvival signal initiation and oxidative phosphorylation in Acute Myeloid Leukemia (AML) cells, leading to complete regression of AML xenografts. These findings suggest a potential application of zelenirstat in AML treatment. googletag.cmd.push(function () { googletag.display('text-ad1'); }); “AML patients, especially those who have exhausted other treatment options, represent a population with significant unmet needs,” Weickert adds. “The promising preclinical evidence, coupled with the Orphan and Fast Track designations granted by the US FDA, positions zelenirstat as a compelling candidate for further clinical investigation in AML.” Investigational New Drug clearance In light of these findings, Pacylex Pharmaceuticals is advancing zelenirstat into a Phase 1/2 clinical study for AML patients, following the clearance of a US Investigational New Drug (IND) application by the US Food and Drink Administration (FDA). “Bringing zelenirstat to AML patients is a top priority for Pacylex Pharmaceuticals,” concludes Weickert. “The urgency stems from the high mortality rates associated with AML, particularly among patients who have exhausted other available therapies. We aim to provide a much-needed therapeutic option to this patient population.” The company says the presentation of phase 1 results for zelenirstat at the World Orphan Drug Congress USA 2024 represents a significant step forward in Pacylex Pharmaceuticals' mission to innovate cancer treatment and improve patient outcomes.

临床1期孤儿药临床申请快速通道临床结果

2024-01-21

·药明康德

延长晚期胰腺癌患者OS近6个月的联合疗法；使脑肿瘤患者超4年疾病无进展的联合疗法... | 一周盘点

▎药明康德内容团队编辑本期看点1. 一项1b期研究数据显示，基于CD73抑制剂quemliclustat的联合治疗方案在未经治疗的转移性胰腺癌患者中具有治疗潜力，患者的总生存期（OS）较单独化疗的历史基准数据延长5.9个月。2. Panbela Therapeutics公司基于CPP-1X（DFMO）的联合疗法在神经母细胞瘤患者中展现积极疗效，3名完成治疗的患者在没有接受额外治疗的情况下，已保持4年多没有出现疾病进展。3. Fostrox联用激酶抑制剂lenvatinib治疗晚期肝细胞癌（HCC）展现积极结果，18周时的疾病控制率（DCR）超过60%。药明康德内容团队整理Quemliclustat：公布1b期临床试验数据 Arcus Biosciences公司与吉利德科学（Gilead Sciences）公司公布了其共同开展的1b期研究ARC-8的OS数据。ARC-8是一项针对既往未经治疗的转移性胰腺导管腺癌（mPDAC）患者的研究，旨在评估一种在研小分子CD73抑制剂quemliclustat（下表中简称“Q”）＋化疗（下表中简称“G/nP”）±一种在研抗PD-1抗体zimberelimab（下表中简称“Z”）的疗效。▲ARC-8研究的疗效数据（图片来源：参考资料[2]）截止2023年6月19日的数据，以quemliclustat为基础的两种治疗方案的中位OS为15.7个月，单独化疗组的历史基准数据为9.8个月。相比于单独化疗组，接受以quemliclustat为基础的两种治疗方案的患者的死亡风险降低了37%（HR=0.63；95% CI：0.47-0.85，p=0.0030）。安全性方面，未发现新的安全性信号。最常见的不良事件（≥3级）是中性粒细胞减少和贫血。CPP-1X（DFMO）：公布1期临床试验数据Panbela Therapeutics公司公布了CPP-1X（DFMO）治疗神经母细胞瘤的临床研究数据。这项发表在British Journal of Cancer上的研究旨在评估大剂量CPP-1X与塞来昔布（celecoxib）联用标准化疗治疗接受过大量先前治疗的神经母细胞瘤患者的耐受性和活性。结果显示，CPP-1X的耐受性良好，患者的中位进展时间（time-to-progression）为19.8个月。最佳总缓解包括2例部分缓解（PR）、4例轻微缓解（MR）、10例疾病稳定（SD）、7例疾病进展（PD）和1例无法评估的患者，无完全缓解（CR）患者。所有总缓解为PR或MR的患者都保持了这种缓解，直到停止或完成治疗。客观缓解率（CR+PR）为9%，任意缓解率（CR+PR+MR）为26%。2年后，该队列的无进展生存率为29.5%。值得注意的是，有3位患者完成了治疗，并且在治疗结束后的四年多时间里，在没有额外治疗的情况下，仍未出现疾病进展。Fostroxacitabine bralpamide（fostrox）：公布1b/2a期临床试验的新数据Medivir公司公布了其正在进行的1b/2a期研究的积极新数据。该研究旨在评估fostrox联用激酶抑制剂Lenvima（lenvatinib）治疗目前一线或二线治疗无效或不能耐受的晚期HCC患者的安全性和疗效。Fostrox是一种核苷酸DNA聚合酶抑制剂口服前药，以肝脏为靶器官，旨在选择性将药物递送到肝细胞中治疗HCC，并将副作用降至最低。该研究目前仍在进行中，约有超过40%的患者仍在接受治疗，仅有5%的人因不良反应而停用fostrox，需要减少剂量的人数也低于预期。该联合疗法的耐受性良好，没有新的、意外的安全事件。此次公布的结果显示，大多数患者都能持续获得临床治疗效果，治疗18周时的DCR高达61%，总缓解率（ORR）为25%，中位进展时间为5.1个月。截至目前，持续缓解时间最长的患者在接受治疗约17个月后仍保持着PR。PMB-CT01：公布1期临床试验中首位患者的数据PeproMene Bio公司公布了其候选CAR-T细胞疗法PMB-CT01治疗复发/难治性急性B淋巴细胞白血病（B-ALL）患者的1期临床试验中首位患者的数据。PMB-CT01是一种潜在“first-in-class”的B细胞活化因子受体（BAFFR）靶向自体CAR-T细胞疗法。BAFFR是肿瘤坏死因子（TNF）受体超家族成员，是BAFF的主要受体，几乎只在B细胞上表达。由于BAFFR信号能促进正常B细胞的增殖，而且似乎是B细胞存活所必需的，因此肿瘤细胞不太可能通过丢失BAFFR抗原来逃避免疫反应。这种独特的特性使BAFFR靶向的CAR-T细胞疗法具有治疗B细胞恶性肿瘤的巨大潜力。BAFFR靶向的CAR-T细胞疗法是使用抗BAFFR scFv（单链可变区）抗体与包含CD3ζ和4-1BB的第2代信号转导结构域构建的。研究发现，BAFFR靶向的CAR-T细胞能在体外和动物模型中杀死人类淋巴瘤和白血病细胞。PeproMene Bio公司已从希望之城（City of Hope）获得与PMB-CT01相关的知识产权许可。此次公布的数据显示，首例患者对PMB-CT01的耐受性良好，只出现了轻微的在预期内的毒性反应，并在接受治疗一个月后达到了CR。AB126：IND申请获得FDA许可Aruna Bio公司宣布美国FDA已批准了其主导项目AB126的IND申请。该公司预计将于2024年上半年启动AB126治疗急性缺血性中风患者的1b/2a期临床试验。AB126是一种未经修饰的神经源性外泌体，天然具有穿越血脑屏障的能力。有证据表明，AB126具有抗炎和神经保护特性。新闻稿指出，AB126是首款进入人体试验阶段的针对神经系统适应症的外泌体疗法。KVA12123：公布1/2期临床试验的新数据Kineta公司公布了其正在进行的1/2期临床试验的最新进展，该试验评估了其新型在研VISTA阻断免疫疗法KVA12123在晚期实体瘤患者中的治疗效果。KVA12123是一种单克隆抗体疗法，需每周输注两次。通过将独特的表位结合与优化的IgG1 Fc区相结合，KVA12123单药在临床前模型中显示出强大的肿瘤生长抑制作用，且在临床试验中没有报告细胞因子释放综合征（CRS）。KVA12123已被证明能降低VISTA靶点的风险，并提供了一种新的方法来解决肿瘤微环境中的免疫抑制问题，其作用机制与以T细胞为重点的疗法不同且互补。此次公布的结果显示，KVA12123的耐受性良好，单药或与帕博利珠单抗联用在任何剂量水平上都未出现剂量限制性毒性或细胞因子相关不良事件。此外，KVA12123单药可与给药剂量成比例地诱导强抗肿瘤活性所需的促炎生物标志物，显示了阻断VISTA的靶向作用。Onvansertib：公布1b期临床试验数据Cardiff Oncology公司公布了其polo样激酶1（PLK1）抑制剂onvansertib二线治疗携带KRAS突变的转移性结直肠癌（mCRC）患者的1b/2期研究结果。Onvansertib是一种潜在“first-in-class”的第三代口服高选择性丝氨酸/苏氨酸PLK1抑制剂，在各种实体瘤中作为单药或与多种化疗药物联合使用均显示出良好的耐受性。此次公布的结果显示，onvansertib+标准疗法（SoC）化疗+贝伐珠单抗的组合疗法的安全性可控，疗效良好。在44%的患者中观察到PR，中位缓解持续时间为9.5个月。早期的循环肿瘤DNA（ctDNA）动力学可以预测治疗效果。这些积极数据促使Cardiff Oncology公司决定启动onvansertib一线治疗携带RAS突变的mCRC患者的临床试验。Zelenirstat（PCLX-001）：公布1期临床试验数据Pacylex Pharmaceuticals公司公布了其N-肉豆蔻酰转移酶（NMT）抑制剂zelenirstat治疗复发/难治性结直肠癌和其他癌症的1期剂量递增的安全性和耐受性研究结果。Zelenirstat是一种潜在“first-in-class”的口服小分子NMT抑制剂，目前正在开发用于治疗白血病、淋巴瘤和实体瘤。在动物模型中，zelenirstat能在体外选择性地杀死癌细胞，并能使血液恶性肿瘤消退，抑制肺癌和乳腺癌的生长。在急性髓细胞性白血病模型中，zelenirstat能杀死白血病干细胞群，并使正常骨髓细胞再生和生长。此次公布的结果显示，在推荐的2期剂量下，zelenirstat延长了胃肠道和其他癌症患者的无进展生存期。其中，一位此前曾接受过7线治疗后复发的晚期结直肠癌患者在接受了zelenirstat治疗后，癌胚抗原（CEA）和肿瘤体积减少了约50%。大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看）[1] Aruna Bio Announces FDA Clearance of IND for Lead Program AB126, Enabling the First Exosome to Enter in Human Clinical Trials for a Neurological Indication. Retrieved January 19, 2024, from https://www.globenewswire.com/news-release/2024/01/16/2809846/0/en/Aruna-Bio-Announces-FDA-Clearance-of-IND-for-Lead-Program-AB126-Enabling-the-First-Exosome-to-Enter-in-Human-Clinical-Trials-for-a-Neurological-Indication.html[2] Data from a Phase 1b Study of Quemliclustat-Based Regimens Showed Promising Overall Survival in Treatment-Naïve Metastatic Pancreatic Cancer. Retrieved January 19, 2024, from https://www.businesswire.com/news/home/20240116940666/en[3] Kairos Pharma Doses First Patients in Phase 1 Trial of Lead Drug Candidate ENV105 with Osimertinib to Improve Therapy Sensitivity for EGFR-Driven Lung Cancer. Retrieved January 19, 2024, from https://www.globenewswire.com/news-release/2024/01/16/2810031/0/en/Kairos-Pharma-Doses-First-Patients-in-Phase-1-Trial-of-Lead-Drug-Candidate-ENV105-with-Osimertinib-to-Improve-Therapy-Sensitivity-for-EGFR-Driven-Lung-Cancer.html[4] FDA CLEARANCE OF AMPLIA'S IND FOR PANCREATIC CANCER TRIAL IN US. Retrieved January 19, 2024, from https://www.prnewswire.com/news-releases/fda-clearance-of-amplias-ind-for-pancreatic-cancer-trial-in-us-302037692.html[5] PeproMene Bio 宣布在 PMB-CT01 1 期临床试验中，B-ALL 患者病情得到完全缓解 | 取得成功. Retrieved January 19, 2024, from https://www.prnasia.com/story/434368-1.shtml[6] Oxford BioTherapeutics Announces First Patient Dosed with OBT076 in Phase 1b Trial in Adenoid Cystic Carcinomas of the Head and Neck. Retrieved January 19, 2024, from https://www.globenewswire.com/news-release/2024/01/18/2811280/0/en/Oxford-BioTherapeutics-Announces-First-Patient-Dosed-with-OBT076-in-Phase-1b-Trial-in-Adenoid-Cystic-Carcinomas-of-the-Head-and-Neck.html[7] Cardiff Oncology Announces Publication of Data from Phase 1b study in second-line KRAS-mutated mCRC in Clinical Cancer Research. Retrieved January 19, 2024, from https://www.prnewswire.com/news-releases/cardiff-oncology-announces-publication-of-data-from-phase-1b-study-in-second-line-kras-mutated-mcrc-in-clinical-cancer-research-302036963.html[8] Sensorion Announces Approval to Initiate Lead Gene Therapy Candidate SENS-501 (OTOF-GT) into a Phase 1/2 Clinical Trial in some European Countries. Retrieved January 19, 2024, from https://www.businesswire.com/news/home/20240118230763/en[9] Vor Bio Doses First AML Patient with VCAR33 (ALLO) and Provides Corporate Update. Retrieved January 19, 2024, from https://ir.vorbio.com/news-releases/news-release-details/vor-bio-doses-first-aml-patient-vcar33-allo-and-provides[10] Panbela Announces Publication of Clinical Data Titled: Phase 1 study of high-dose DFMO, celecoxib, cyclophosphamide and topotecan for patients with relapsed neuroblastoma: A New Approaches to Neuroblastoma Therapy Trial. Retrieved January 19, 2024, from https://www.globenewswire.com/news-release/2024/01/18/2811519/37414/en/Panbela-Announces-Publication-of-Clinical-Data-Titled-Phase-1-study-of-high-dose-DFMO-celecoxib-cyclophosphamide-and-topotecan-for-patients-with-relapsed-neuroblastoma-A-New-Approa.html[11] Kineta Provides Update on its Ongoing Phase 1/2 VISTA-101 Clinical Trial of KVA12123 in Patients with Advanced Solid Tumors. Retrieved January 19, 2024, from https://kinetabio.com/2024/01/17/kineta-provides-update-on-its-ongoing-phase-1-2-vista-101-clinical-trial-of-kva12123-in-patients-with-advanced-solid-tumors/[12] Enlivex Receives IMOH Regulatory Authorization for the Initiation of a Multi-Country, Randomized, Controlled Phase I/II Trial Evaluating Allocetra in Up To 160 Patients with Moderate to Severe Knee Osteoarthritis. Retrieved January 19, 2024, from https://www.globenewswire.com/news-release/2024/01/17/2810641/0/en/Enlivex-Receives-IMOH-Regulatory-Authorization-for-the-Initiation-of-a-Multi-Country-Randomized-Controlled-Phase-I-II-Trial-Evaluating-Allocetra-in-Up-To-160-Patients-with-Moderate.html[13] Biomica Successfully Completes Phase I Trial Enrollment for Microbiome-Based Immuno-Oncology Drug. Retrieved January 19, 2024, from https://www.prnewswire.com/news-releases/biomica-successfully-completes-phase-i-trial-enrollment-for-microbiome-based-immuno-oncology-drug-302036967.html[14] Evommune Announces Initiation of a Phase 1 Trial of its MRGPRX2 Antagonist for the Treatment of Chronic Spontaneous Urticaria. Retrieved January 19, 2024, from https://www.prnewswire.com/news-releases/evommune-announces-initiation-of-a-phase-1-trial-of-its-mrgprx2-antagonist-for-the-treatment-of-chronic-spontaneous-urticaria-302037378.html[15] Inflammasome Therapeutics Announces First Patient Dosed in Phase I Diabetic Macular Edema Study of the Dual Inflammasome Inhibitor K8. Retrieved January 19, 2024, from https://www.businesswire.com/news/home/20240118557124/en[16] Fostrox + Lenvima shows further improved response rates and time to progression in advanced liver cancer (HCC) at ASCO GI Symposium. Retrieved January 19, 2024, from https://www.prnewswire.com/news-releases/fostrox--lenvima-shows-further-improved-response-rates-and-time-to-progression-in-advanced-liver-cancer-hcc-at-asco-gi-symposium-302036736.html[17] Pacylex Pharmaceuticals Reports Phase 1 Safety and Efficacy Results for Zelenirstat in Colorectal and other Cancers. Retrieved January 19, 2024, from https://www.newsfilecorp.com/release/194619免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床2期临床结果

2024-01-21

·今日头条

补充剂能改善儿童呼吸道感染吗？大型荟萃分析探究竟 | 热心肠日报

01月21日的《热心肠日报》，我们解读了 15 篇文献，关注：膳食补充剂，儿童，孕妇，认知功能，更年期，植物性饮食，微生物食品，乳化剂，1型糖尿病，生酮饮食，Ibezapolstat，Pragma Bio，DayTwo，Fitbit，Quest Diagnostics，Zelenirstat。该篇日报由R·AI辅助创作生成，人工审核校对。儿童呼吸道感染的营养干预 Allergy: European Journal of Allergy and Clinical Immunology——[12.4] ① 一项系统评价和荟萃分析的结果显示，目前尚无具体的膳食/营养干预措施可推荐用于儿童呼吸道感染的常规治疗；② 纳入50项研究进行荟萃分析，评估锌、维生素A、维生素E、维生素D、益生菌等膳食/营养干预措施对儿童剂型呼吸道感染的影响；③ 不同的膳食干预措施对临床结果影响不一，有些显示积极效果，而其他则无显著影响；④ 在肺炎患儿中，补充锌可有限地减少住院时间，但对恢复时间无显著影响；⑤ 在肺炎患儿中，补充维生素D无任何效果；⑥ 未来需要进一步研究以获得更具说服力的证据，特别是针对高收入国家环境下的儿童。【原文信息】 A systematic review and meta-analysis on nutritional and dietary interventions for the treatment of acute respiratory infection in pediatric patients: An EAACI taskforce 2024-01-04 , doi: 10.1111/all.15997 NEJM：低剂量钙补充剂的孕期疾病预防效果 New England Journal of Medicine——[158.5] ① 世界卫生组织推荐膳食摄入钙较低的孕妇可每日补充1500mg的钙补充剂以降低子痫前期风险，但由于给药方法复杂和成本问题，患者依从性较低；② 目前有报道每日低剂量钙补充剂（500mg）与高剂量（1500mg）在孕妇子痫前期风险降低上疗效相当，因此本研究进行了双中心试验（印度和坦桑尼亚）以比较两种剂量钙补充剂对孕妇的影响；③ 印度试验中，低剂量和高剂量组的妊娠期高血压疾病发生率分别为3.0%和3.6%，早产率分别为11.4%和12.8%，组间无显著差异；④ 坦桑尼亚试验中，低剂量和高剂量组的妊娠期高血压疾病发生率分别为3.0%和2.7%，早产率分别为10.4%和9.7%，在早产发生上低剂量组超出了非劣效性标准。【原文信息】 Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy 2024-01-11 , doi: 10.1056/NEJMoa2307212 补充复合维生素和矿物质，或可减缓老年认知衰退 American Journal of Clinical Nutrition——[7.1] ① 通过对COSMOS（可可补充剂和复合维生素研究）认知子研究进行荟萃分析（共5203受试者），以全面评估服用复合维生素矿物质（MVM）对认知的影响；② 在COSMOS-Clinic子研究中，相比安慰剂组，MVM对全局认知在2年内有轻微益处，在叙事记忆方面改善更显著，而在执行功能/注意力方面没有显著变化；③ COSMOS子研究的荟萃分析显示MVM对全局认知和叙事记忆有明显益处；④ 对全局认知的影响程度相当于减缓认知老化2年，这些结果支持每日服用MVM在预防老年人认知衰退方面的益处。【原文信息】 Effect of multivitamin-mineral supplementation versus placebo on cognitive function: Results from the clinic sub-cohort of the COSMOS randomized clinical trial and meta-analysis of three cognitive studies within COSMOS 2024-01-18 , doi: 10.1016/j.ajcnut.2023.12.011 植物补充剂或可改善更年期症状 Phytotherapy Research——[7.2] ① 本研究通过系统评价和荟萃分析确认了食用植物源膳食补充剂在改善更年期症状方面的显著效果，包括减少潮热频率和改善更年期评分量表等指标；② 研究对象为年龄在38-85岁的围绝经期或绝经后妇女，大多数出现潮热症状；③ 研究结果显示，食用植物源膳食补充剂可以显著缓解更年期症状，但当前证据的质量和异质性问题需要进一步研究加以确定；④ 食用植物源膳食补充剂可以有效缓解心力衰竭，这主要归因于植物的雌激素作用；⑤ 食用植物源膳食补充剂可能成为改善更年期症状的一种选择，但仍需要更多高质量研究来验证其效果和安全性。【原文信息】 Efficacy of plant-derived dietary supplements in improving overall menopausal symptoms in women: An updated systematic review and meta-analysis 2024-01-08 , doi: 10.1002/ptr.8112 植物性饮食与哪些肠道菌群特征有关？ American Journal of Clinical Nutrition——[7.1] ① 纳入巴尔的摩纵向衰老研究中的705名成年参与者，研究不同植物性饮食指数与成人肠道菌群的横截面关联；② 参与者中55.6%为女性，32.5%为非西班牙裔白人；③ 健康植物性饮食指数（hPDI）与菌群α多样性正相关，而不健康植物性饮食指数（uPDI）则呈负相关；④ hPDI与3种多糖降解细菌（普氏粪杆菌、挑剔真杆菌和多形拟杆菌）的相对丰度正相关；⑤ hPDI还与6种细菌及微生物代谢产物氧化三甲胺负相关；⑥ 因此，需要更加坚持与积极健康菌群特征有关的植物性饮食。【原文信息】 Plant-Based Diets and the Gut Microbiome: Findings from the Baltimore Longitudinal Study of Aging 2024-01-11 , doi: 10.1016/j.ajcnut.2024.01.006 微生物，未来太空食品新选择？（观点） Trends in Biotechnology——[17.3] ① 未来太空任务面临着营养物质供应的挑战，而微生物如微藻和蓝藻可以为宇航员提供食物、药品、纯氧和生物高分子，成为构建太空循环生物再生生命保障系统（BLSS）的重要资源；② 光自养微生物（微藻或蓝藻）可以通过光合作用生产食物，将船员产生的二氧化碳与就地资源利用（ISRU）光结合起来转化为可食用的生物质，还具有产氧、水净化以及废物回收利用的能力；③ 虽然微生物可以生产太空食品，但也必须遵守安全性、稳定性、适口性、可靠性等食品标准以及与太空设备的兼容性；④ 微生物的繁殖能力不仅降低了初始发射成本，而且最大限度地减少了在太空中频繁补给任务的需要，整合ISRU，包括利用阳光、大气原料、机组人员产生的残留物和矿物质，以及微生物来生产生物质、营养物质、生物聚合物和空气，可以显著降低高效和可持续循环BLSS的再补给相关的费用；⑤ 综上所述，微生物在有效合成蛋白质、脂质和氨基酸等必需营养分子方面发挥着关键作用，同时通过吸收二氧化碳并将其转化为氧气来治理废物。【原文信息】 Microbial products for space nutrition 2024-01-04 , doi: 10.1016/j.tibtech.2023.12.004 膳食乳化剂会促进1型糖尿病吗？ NPJ Biofilms and Microbiomes——[9.2] ① 探究两种膳食乳化剂，羧甲基纤维素和聚山梨酯-80，是否会影响非肥胖型糖尿病（NOD）小鼠1型糖尿病（T1D）的发展；② 乳化剂暴露会加速NOD小鼠T1D发展，与胰岛素自身抗体水平升高有关；③ NOD小鼠肠道菌群组成在食用乳化剂后发生改变，其摄入会增加小鼠微生物群的促炎潜能；④ 乳化剂的摄入会诱导NOD小鼠微生物群的入侵和微生物群靶向抗体的产生，造成肠上皮损伤和低级别肠道炎症；⑤ 机器学习发现乳化剂引起的菌群破坏的严重程度可部分预测随后的疾病发展。【原文信息】 Dietary emulsifier consumption accelerates type 1 diabetes development in NOD mice 2024-01-06 , doi: 10.1038/s41522-023-00475-4 生酮饮食对炎症标志物的影响 Nutrition Reviews——[6.1] ① 一项系统评价和荟萃分析发现，生酮饮食对降低炎症标志物TNF-α和IL-6水平具有显著效果，但对其它标志物影响不显著；② 在进行生酮饮食≤8周且年龄≤50岁的试验中，TNF-α水平的下降明显超过其他组；③ 在BMI大于30 kg/m2的人群中，接受生酮饮食后IL-6水平下降更显著；④ 生酮饮食可能有助于改善与炎症相关标志物，进一步探究生酮饮食对不同年龄和体重群体的影响，有助于更好地理解其在炎症调节中的作用机制。【原文信息】 The effect of a ketogenic diet on inflammation-related markers: a systematic review and meta-analysis of randomized controlled trials 2024-01-14 , doi: 10.1093/nutrit/nuad175 Nature子刊：一文读懂酮体（综述） Nature Metabolism——[20.8] ① 酮体主要由肝脏内源性合成，也可通过各种途径外源性输入；② 酮体可作为三羧酸循环和其他各种生物合成途径的碳源，并发挥着多种信号作用，如抑制NLRP3炎症小体、调节表观遗传、改变基因表达和细胞功能；③ 酮体除作为癫痫的一种有效治疗方法外，也显示出治疗其他神经系统疾病和神经退行性疾病的前景；④ 向衰竭心脏输送酮体可能会通过代谢和信号机制对临床结果产生积极影响；⑤ 酮体正迅速成为防治众多慢性人体免疫代谢疾病的一种治疗选择。【原文信息】 Metabolic Messengers: ketone bodies 2023-12-13 , doi: 10.1038/s42255-023-00935-3 硒蛋白P缺乏与老年人多种疾病死亡风险强相关 European Journal of Epidemiology——[13.6] ① 对德国队列ESTHER研究进行回顾分析，纳入基线（7186名）和5年随访期（4164名）受试者的健康评估和血清硒蛋白P（SELENOP）数据进行关联分析；② 结果表明SELENOP浓度与全因及特定原因死亡率呈负相关，男性相关性更显著；③ SELENOP浓度低于4.1 mg/L（下三位数附近）时死亡率显著升高，低于下三位数的参与者全因死亡率显著增加，且与心血管、癌症、呼吸系统和消化系统疾病死亡率相关；④ 研究结果暗示血清SELENOP浓度可能与多器官中的硒输送和缺乏有关，未来需要进行试验以测试在基线SELENOP浓度低的受试者中硒补充剂的有效性。【原文信息】 Strong associations of serum selenoprotein P with all-cause mortality and mortality due to cancer, cardiovascular, respiratory and gastrointestinal diseases in older German adults 2024-01-10 , doi: 10.1007/s10654-023-01091-4 Acurx公布Ibezapolstat预防CDI复发2b期试验积极数据 ① 1月17日，Acurx Pharmaceuticals公司对外公布了预防艰难梭菌感染（CDI）复发管线药物Ibezapolstat，其2b期临床试验微生物学积极数据；② 分析数据显示，在治疗的第三天，Ibezapolstat组粪便中艰难梭菌清除率为94%（15/16），万古霉素组为71%（10/14）；③ Ibezapolstat能够有效促进和维持肠道有益菌生长，这些菌株有益于预防CDI复发；④ Acurx Pharmaceuticals公司正积极与FDA、欧洲药监局和其它地区的监管机构商讨开展3期临床研究，更多2b期临床数据将不日公布。【原文信息】 Acurx Announces Positive Comparative Microbiology and Microbiome Data for Ibezapolstat from Phase 2b Clinical Trial in CDI Patients 2024-01-17 , Acurx Pharmaceuticals Pragma Bio与DayTwo合作开展IBD研究 ① 近日，Pragma Bio与DayTwo两家公司宣布，将共同开展人体肠道菌群与炎症性肠病（IBD）发病研究，挖掘与IBD相关的生物标志物和新型小分子治疗药物；② Pragma Bio公司在宏基因组、合成生物学和免疫学研究方面具有丰富的经验；③ DayTwo公司专注于开展微生物组研究，拥有全球最大的人体粪便样本宏基因组数据库；④ 未来，双方合作成果将有助于人类了解IBD发病机制，使患者接受更有针对性治疗，以及推动新型IBD药物开发。【原文信息】 Pragma Bio and DayTwo Join Forces to Illuminate the Path to IBD Disease Management 2024-01-17 , Businesswire 韦仕敦大学与克利夫兰诊所共同获资助开展克罗恩病研究 ① 近日，加拿大韦仕敦大学与美国克利夫兰诊所共同获得了慈善组织Helmsley Charitable Trust一笔650万加元（约合人民币3468.9万元）的资助；② 双方科研人员将组建一只交叉学科研究团队，为永久使用回肠造口术的克罗恩病患者开发新型护理方案和药物，最终改善其生活质量；③ 研究团队将包括克罗恩病患者、外科医师、护士、饮食专家和临床研究人员，美加两地的克罗恩病患者将有机会参与其中。【原文信息】 $6.5 million grant to help improve care for Crohn’s disease patients 2024-01-17 , Western News Fitbit和Quest Diagnostics合作，利用可穿戴数据研究代谢健康 ① 1月17日，Fitbit和Quest Diagnostics宣布合作开展名为“代谢健康可穿戴设备（WEAR-ME）”的试点研究；② WEAR-ME试点研究将结合Fitbit设备检测到的行为和生物识别数据以及Quest Diagnostics实验室检测收集的健康信息，来评估代谢健康，并为预防疾病提供见解；③ 该研究旨在根据客观的实验室测试结果评估可穿戴设备对用户行为的影响；④ 约1500名Fitbit用户将参与研究，预计于2024年完成。【原文信息】 Fitbit and Quest Diagnostics Collaborate to Advance Research on the Use of Wearable Devices to Improve Metabolic Health 2024-01-17 PACYLEX公布Zelenirstat 1期临床积极结果 ① 1月17日，加拿大生物制药公司PACYLEX宣布，候选药物Zelenirstat在治疗结直肠癌和其它癌症的1期临床试验中取得积极结果；② 1期临床共招募了29名曾接受过4线以上治疗的实体瘤和淋巴瘤患者，均为难治性或复发性肿瘤患者；③ 研究发现，候选药物Zelenirstat能延长肿瘤患者的疾病无进展生存期和总生存期；④ 结直肠癌患者实现病情长期稳定，癌胚抗原减少50%以上，肿瘤体积缩小，阑尾癌患者也实现160天以上的病情稳定。【原文信息】 Phase 1 Safety and Efficacy Results for Zelenirstat in Colorectal and other Cancers 2024-01-17 , Pacylex 感谢本期日报的审核者：mildbreeze，aluba，Johnson，九卿臣，RZN，圆圈儿，orchid，注册营养师陈彬林，Richard，lxx 点击阅读过去10天的日报： 0120 | Cell重磅：论菌群的"社会性"及其对健康的影响 0119 | 今日Cell：母乳如何守护宝宝肠道？新机制揭晓 0118 | 刘双江/刘宏伟/姜长涛Nature子刊：小克里斯滕森氏菌生成新型胆汁酸，改善代谢 0117 | 肠炎或促脂肪肝？国内团队揭示肠肝轴机制 0116 | Science子刊揭秘：肠道免疫细胞的全身"旅行"图谱 0115 | 胃肠癌风险有多高？国内团队Lancet子刊重磅发布全球性研究 0114 | 限时进食改善肥胖和代谢，效果如何？29分综述一览最全证据 0113 | 多文聚焦：新方法新技术，助菌群研究更上一层楼 0112 | 高分Cell子刊：郑啸/郝海平和吴浩等在肠脑轴和营养研究中各有新斩获 0111 | Nature锐评：推动菌群研究全球化，功在千秋

临床研究

100 项与 Zelenirstat 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15567

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
弥漫性大B细胞淋巴瘤	临床2期	-	Pacylex Pharmaceuticals, Inc.	2023-07-12
非洲锥虫病	临床2期	英国	University Of Dundee	-
非洲锥虫病	临床2期	英国	Wellcome Trust Clinical Research Facility	-
晚期恶性实体瘤	临床1期	加拿大	Pacylex Pharmaceuticals, Inc.	2021-09-14
难治性B细胞淋巴瘤	临床1期	加拿大	Pacylex Pharmaceuticals, Inc.	2021-09-14
急性髓性白血病	临床申请批准	美国	Pacylex Pharmaceuticals, Inc.	2022-11-04

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04836195 (NEWS) 人工标引	临床1期	实体瘤 \| 淋巴瘤	29	Zelenirstat	(積衊糧製選淵鬱餘淵醖) = The most common treatment related adverse events identified in the trial were mild to moderate gastrointestinal side effects which were self-limiting and occurred in a minority of patients. 壓鹹觸鬱衊鏇觸襯艱糧 (醖範簾糧構憲壓餘齋製 ) 更多	积极	2023-11-30
NCT04836195 (ASCO2023) 人工标引	临床1期	实体瘤 \| B细胞淋巴瘤	18	PCLX-001	(糧觸壓鹹齋憲獵蓋願鬱) = 憲廠鹹鬱憲淵衊廠蓋鬱簾齋鏇憲繭鹹鬱醖膚觸 (獵範繭淵鬱構鏇構選觸 ) 更多	积极	2023-05-26
AACR2024	临床1期	-	24	Zelenirstat	(鏇構夢憲壓製鏇遞範鹹) = 構餘簾鑰願醖艱齋淵製選鹹構遞積鬱願簾顧鏇 (膚廠憲衊壓選構築鹹範 ) 更多	积极	2024-04-05
AACR2023	N/A	生殖细胞癌	-	PCLX-001	(獵鹹襯簾鹽廠積蓋鬱艱) = Myristoylated mitochondrial protein NDUFAF4, a major complex I assembly factor, was the most downregulated 築鏇餘憲蓋鬱糧窪糧夢 (觸糧構鬱簾鹹製齋艱構 ) 更多	-	2023-04-04
NCT04836195 (ASCO_GI2024) 人工标引	临床1期	晚期恶性实体瘤 \| B细胞淋巴瘤	21	zelenirstat	(願鬱齋鹹鏇膚願構糧繭) = DLT was not observed up to and including the 210 mg/d cohort.Gastrointestinal DLTs were seen in the 280 mg/d cohort 鹹簾襯鹹鹽網鏇糧壓衊 (膚鑰遞鹽廠淵夢壓簾夢 ) 更多	积极	2024-01-20