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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141

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 ; Otani, Satoru ; Li, Shengtian ; Zhang, Liangui ; Chen, Fujun

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

Abstract:

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

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）

2024-06-10

·BioSpace

Pacylex Publishes Phase 1 Safety and Efficacy of Zelenirstat in Cancer Patients in the Journal Investigational New Drugs

Edmonton, Alberta--(News - June 10, 2024) - Pacylex Pharmaceuticals Inc. (Pacylex) is a clinical-stage pharmaceutical company developing N-myristoyltransferase (NMT) inhibitors to treat hematologic cancers and solid tumors. Today Pacylex announced the publication of Phase 1 clinical trial results in the journal Investigational New Drugs. The report, titled: "A First-in-Human Phase I Trial of Daily Oral Zelenirstat, a N-myristoyltransferase Inhibitor, in Patients with Advanced Solid Tumors and Relapsed/Refractory B-cell Lymphomas," describes effects of zelenirstat at various doses on cancer patients who exhausted all other therapeutic options. To view the full announcement, including downloadable images, bios, and more, click here. Key Takeaways: Zelenirstat was well tolerated, and adverse events were primarily gastrointestinal side effects, most of which resolved spontaneously without dose reduction. Patients with heavily pre-treated colorectal, appendiceal, and ovarian cancers had 6 to 16 months of stable disease when treated with the recommended Phase 2 dose. Zelenirstat inhibits myristoylation of proteins involved in several key cancer-driving processes explaining its broad spectrum of activity. Click image above to view full announcement. About Zelenirstat (PCLX-001) Zelenirstat (formerly identified as PCLX-001) is a first-in-class, oral, small molecule NMTi being developed to treat patients with leukemia, lymphoma, and solid tumors. Zelenirstat selectively killed cancer cells in vitro and in animal models has been shown to fully regress hematologic malignancies and inhibit the growth of lung and breast cancer tumors. In AML models, zelenirstat preferentially killed leukemic stem enriched cell populations and reduced the bone marrow leukemic burden. About Zelenirstat Phase 1 and 2 Studies Pacylex completed the dose escalation phase of a Phase 1 multiple ascending dose safety, tolerability, and pharmacokinetics study on zelenirstat in people with relapsed/refractory lymphoma and refractory solid tumors (NCT04836195). A recommended Phase 2 dose was determined. Zelenirstat demonstrated an acceptable safety and tolerability profile, pharmacokinetics consistent with once daily oral dosing, and early signs of efficacy. Zelenirstat is currently being studied in a Phase 2a open-label study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of zelenirstat in patients with relapsed/refractory B-cell non-Hodgkin Lymphoma (NHL) and a separate Phase 2a cohort in patients with refractory metastatic colorectal cancer that has progressed despite all available standard therapies. About Pacylex Pharmaceuticals Pacylex is a clinical-stage pharmaceutical company headquartered in Edmonton, Alberta, Canada, targeting hematologic and solid cancers with orally bioavailable NMT inhibitors. Zelenirstat is the lead drug in a new class of NMT inhibitors, enabling Pacylex to exploit NMTs as new clinical targets for cancer treatment. Pacylex is conducting two multi-center Phase 2a studies in Canada in patients with relapsed/refractory NHL and refractory metastatic colorectal cancer. The IND for a Phase 1 multiple ascending dose study in acute myeloid leukemia (AML) has been cleared and the FDA has granted zelenirstat both Orphan Drug Designation and Fast Track Designation for AML. The US Department of Defense is supporting the initial clinical investigation of zelenirstat in patients with AML. The Cure Cancer Foundation supported initial clinical studies through its World's Longest Games. Contacts: Michael Weickert Ph.D 650-218-1840 michael.weickert@pacylex.com Source: Pacylex To view the source version of this press release, please visit

临床1期孤儿药临床结果快速通道临床2期

2024-06-02

·药明康德

疾病控制率近97%的肺癌联合疗法；有望逆转功能衰退的创新渐冻症疗法进入临床…… | 一周盘点

▎药明康德内容团队编辑本期看点1. 应世生物（InxMed）公布了ifebemtinib联用garsorasib一线治疗携带KRAS G12C突变的非小细胞肺癌（NSCLC）的早期临床试验结果，31例可评估患者的客观缓解率（ORR）达90.3%，疾病控制率（DCR）为96.8%。2. Enterome公司基于肿瘤肽的免疫疗法EO2463联用来那度胺和利妥昔单抗治疗惰性非霍奇金淋巴瘤（NHL），在一项1/2期临床试验中的完全缓解（CR）率达78%。3. 美国FDA批准了N-肉豆蔻酰转移酶（NMT）抑制剂SPG302的IND申请，该疗法具有恢复突触的独特能力，有望逆转肌萎缩性脊髓侧索硬化（ALS）患者的认知、呼吸和运动功能的衰退。药明康德内容团队整理Ifebemtinib：公布1b/2期临床试验数据应世生物公布了其黏着斑激酶（FAK）抑制剂ifebemtinib联用KRAS G12C突变特异性抑制剂garsorasib一线治疗携带KRAS G12C突变的NSCLC的1b/2期临床试验结果。Ifebemtinib是一种高选择性、口服小分子FAK抑制剂，与化疗药物、靶向疗法和免疫疗法具有协同作用。迄今为止，已有600多名患者接受了ifebemtinib治疗，观察到了良好的安全性和耐受性。截至2024年5月10日的数据，共有33名受试者参与了这项研究。在31名可评估的患者中，ORR为90.3%，DCR为96.8%。28例患者达到了部分缓解（PR），其中26人已得到确认，2例患者达到了疾病稳定（SD）。Ifebemtinib与garsorasib联合治疗的总体安全性与ifebemtinib或garsorasib单药治疗一致，大多数治疗相关不良事件为1级或2级。EO2463：公布1/2期临床试验的新数据 Enterome公司公布了其基于肿瘤肽的免疫疗法EO2463单药和与来那度胺和/或利妥昔单抗联用治疗惰性NHL的效果。EO2463由4种模拟B细胞肿瘤相关抗原CD20、CD22，CD37和CD268（BAFF受体）的多肽以及辅助性的UCP2肽组成，能够激活抗肿瘤免疫反应，清除癌变B细胞。此次公布的结果显示，EO2463单药治疗6周后即可观察到有益的临床应答，9例患者中4例（44%）患者的代谢标志物有减少或肿瘤尺寸缩小。接受EO2463联用来那度胺和利妥昔单抗治疗患者的CR率为78%（7/9），包括5例放射学CR。EO2463可迅速扩增靶向OncoMimics多肽和B细胞抗原的特异性记忆CD8 T细胞，从而诱发快速且强力的细胞毒性反应，这种细胞毒性反应目前已维持长达94周。SPG302：IND申请获得FDA许可 Spinogenix公司宣布，美国FDA已经批准了SPG302治疗肌萎缩性脊髓侧索硬化的1/2期临床试验的IND申请。该试验将评估SPG302在ALS患者中的安全性、耐受性、药代动力学（PK）和药效学。SPG302是一种正在被开发用于治疗ALS和其他神经退行性疾病的再生疗法，每日只需服用一次。它具有恢复突触的独特能力，有望逆转患者认知、呼吸和运动功能的衰退。Zelenirstat（PCLX-001）：公布1期临床试验数据 Pacylex Pharmaceuticals公司公布了其NMT抑制剂zelenirstat治疗复发/难治性淋巴瘤和难治性实体瘤的1期剂量递增安全性和耐受性研究的结果。Zelenirstat是一种潜在“first-in-class”的口服小分子NMT抑制剂，目前正在被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。在急性髓系白血病模型中，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，接受推荐的2期剂量7名患者的无进展生存期和总生存期明显优于接受较低剂量治疗的17名患者。这些患者的癌症类型不同（5种），57%的患者保持SD或更好的治疗结果≥6个月。在1名结直肠（CRC）癌患者身上观察到了长期的SD，该患者之前接受的6种疗法中的任何一种都只能带来了短期疗效，而在接受了zelenirstat治疗后，癌胚抗原（CEA）和肿瘤体积减少了约50%。此外，zelenirstat的耐受性良好，不良事件主要是胃肠道副作用，其中大部分能够自行消退，无需减少剂量。TTX-MC138：公布0期临床试验的初步数据 TransCode Therapeutics公司公布了其主要治疗候选药物TTX-MC138的0期临床试验的最新初步数据，表明其具有抗肿瘤活性。TTX-MC138旨在抑制促转移RNA——microRNA-10b，它被认为是多种晚期实体瘤转移的主要调节因子。在临床前研究中，TTX-MC138展现出对多种癌症模型的有效性，包括乳腺癌、胰腺癌、卵巢癌、结肠癌、胶质母细胞瘤等等。此次公布的结果显示，TTX-MC138能显著抑制患者血液中的miRNA-10b，miRNA-10b在给药后的24小时内减少了66%。此外，TTX-MC138的耐受性良好，未发现任何不良反应。Dapiglutide：公布早期临床试验的数据 Zealand Pharma公司公布了其胰高血糖素样肽（GLP）1受体/GLP-2受体双激动剂dapiglutide治疗肥胖的最新临床试验结果。Dapiglutide是一种潜在“first-in-class”的长效肽疗法，旨在利用强效GLP-1激动剂的效果来减重，并通过GLP-2的肠道屏障改善功能来解决与低级别炎症相关的并发症。此次公布的结果显示，接受低剂量dapiglutide治疗12周后，患者的体重平均减轻了4.3%。此外，dapiglutide的耐受性良好。此前公布的药代动力学数据显示，4个剂量组的平均半衰期为123-129小时，支持每周一次的给药频率。一项为期13周的1b期试验正在评估更高剂量的dapiglutide，预计将于2024年下半年获得顶线结果。NC410：公布1b期临床试验数据 NextCure公司公布了其LAIR-2融合蛋白NC410联用pembrolizumab的1b期临床试验的数据。结果显示，在37例可评估、未接受过免疫检查点抑制剂（ICI）治疗、微卫星稳定/微卫星不稳定性低（MSS/MSI-L）、没有肝转移的结直肠癌患者中，有2例达到了确认的PR，17例达到了SD，DCR为51%，疾病控制的中位持续时间为5.5个月。在7名可评估的卵巢癌患者中，有3例达到了PR，DCR为43%。其中，1人持续缓解了7.9个月，1人持续缓解了4.1个月，还有1人已持续缓解了5.1个月，并仍在持续缓解中。SRK-181：公布1期临床试验数据 Scholar Rock公司公布了其旨在克服晚期癌症患者对检查点治疗耐药性的单克隆抗体SRK-181的1期临床试验数据。TGFβ1是在许多人类肿瘤类型中表达的主要TGFβ亚型。研究表明，TGFβ1是免疫抑制肿瘤微环境的关键贡献者。SRK-181是一种选择性的潜在TGFβ1激活抑制剂，与抗PD-1/PD-L1疗法联合使用时，有潜力克服检查点治疗耐药问题，同时可能避免其他非选择性TGFβ抑制方法存在的心脏毒性。此次公布的数据显示，在多种癌症类型中观察到SRK-181令人鼓舞的治疗效果，包括透明细胞肾细胞癌、头颈部鳞状细胞癌、黑色素瘤和尿路上皮癌。生物标志物数据显示，SRK-181联用帕博利珠单抗在抗PD-1/PD-L1疗法耐药患者中创造了增强的促炎微环境。此外，SRK-181具有良好的耐受性。BE-101：IND申请获得FDA许可 Be Biopharma公司宣布美国FDA批准了其潜在“first-in-class”的自体B细胞疗法（BCM）BE-101的IND申请。BE-101旨在将人类FIX基因插入原代人类B细胞，从而表达可治疗血友病B的活性FIX。在临床前研究中，单次使用BE-101已被证明能够提供具活性和持续的FIX水平。数据证实了表达FIX的BCM能够在骨髓组织中按预期分布，并能在骨髓组织中长期稳定地定植。此外，BE-101的可重复给药性也得到了证实，血浆FIX水平如预期增加。该公司计划在2024年下半年启动一项1/2期临床试验，以评估BE-101在中重度至重度血友病B成年患者中的安全性和初步疗效。▲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] Affini-T Therapeutics Announces First Patient Dosed in KRAS G12V Phase 1 Program and Presentation of Trial-in-Progress Poster at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240528503183/en[2] selectION Announces Initiation of Phase 1b Clinical Trial Evaluating si-544 in Patients with Psoriasis Vulgaris or Psoriatic Arthritis. Retrieved May 31, 2024, from https://selectiontherapeutics.com/selection-announces-initiation-of-phase-1b-clinical-trial-evaluating-si-544-in-patients-with-psoriasis-vulgaris-or-psoriatic-arthritis/[3] SOTIO Announces First Patient Dosed in Phase 1 Clinical Study of SOT201 for Patients with Solid Tumors. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240528380813/en[4] HiberCell Announces First Patient Dosed in Phase 1b Clinical Trial, Evaluating HC-7366 in Combination with Venetoclax and Azacitidine for the Treatment of Acute Myeloid Leukemia (AML). Retrieved May 31, 2024, from https://www.globenewswire.com/news-release/2024/05/28/2888943/0/en/HiberCell-Announces-First-Patient-Dosed-in-Phase-1b-Clinical-Trial-Evaluating-HC-7366-in-Combination-with-Venetoclax-and-Azacitidine-for-the-Treatment-of-Acute-Myeloid-Leukemia-AML.html[5] Be Biopharma Announces FDA Clearance of IND Application for BE-101 in Hemophilia B. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240528592948/en[6] Spinogenix Announces FDA Clearance of IND Application for SPG302, a Novel Therapy for the Treatment of ALS. Retrieved May 31, 2024, from https://www.globenewswire.com/en/news-release/2024/05/29/2889788/0/en/Spinogenix-Announces-FDA-Clearance-of-IND-Application-for-SPG302-a-Novel-Therapy-for-the-Treatment-of-ALS.html[7] Full-Life Technologies Announces Clearance from FDA of IND Application for 225Ac-FL-020 for the Treatment of Metastatic Castration-Resistant Prostate Cancer. Retrieved May 31, 2024, from https://www.prnewswire.com/news-releases/full-life-technologies-announces-clearance-from-fda-of-ind-application-for-225ac-fl-020-for-the-treatment-of-metastatic-castration-resistant-prostate-cancer-302156355.html[8] TransCode Therapeutics Reports Positive Data from First-in-Human Clinical Study Using Novel Lead Therapeutic Candidate, TTX-MC138. Retrieved May 31, 2024, from https://www.globenewswire.com/news-release/2024/05/29/2889976/0/en/TransCode-Therapeutics-Reports-Positive-Data-from-First-in-Human-Clinical-Study-Using-Novel-Lead-Therapeutic-Candidate-TTX-MC138.html[9] Kiromic BioPharma Reports Favorable Results at Six Weeks from Fourth Patient in Deltacel-01 Clinical Trial. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240529675813/en[10] Biohaven Doses First Patient with its Novel Trop-2 Directed Antibody Drug Conjugate (ADC) BHV-1510 in Advanced or Metastatic Epithelial Tumors. Retrieved May 31, 2024, from https://www.prnewswire.com/news-releases/biohaven-doses-first-patient-with-its-novel-trop-2-directed-antibody-drug-conjugate-adc-bhv-1510-in-advanced-or-metastatic-epithelial-tumors-302157427.html[11] Actym Therapeutics Announces IND Clearance for Phase 1 Clinical Trial Investigating Lead Program ACTM-838 in Patients with Solid Tumors. Retrieved May 31, 2024, from https://www.prnewswire.com/news-releases/actym-therapeutics-announces-ind-clearance-for-phase-1-clinical-trial-investigating-lead-program-actm-838-in-patients-with-solid-tumors-302159288.html[12] Strand Therapeutics Announces First Patient Dosed with Programmable mRNA Therapy STX-001 in Phase 1 Trial for Solid Tumors. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240530103588/en/[13] NextCure Presents Phase 1b Data on NC410 and Pembrolizumab Combination at ASCO 2024. Retrieved May 31, 2024, from https://www.globenewswire.com/news-release/2024/05/30/2891119/0/en/NextCure-Presents-Phase-1b-Data-on-NC410-and-Pembrolizumab-Combination-at-ASCO-2024.html[14] Zealand Pharma announces topline results from the mechanistic investigator-led DREAM trial with low doses of GLP-1/GLP-2 receptor dual agonist dapiglutide. Retrieved May 31, 2024, from https://www.zealandpharma.com/media/zealand-news/[15] Enterome Highlights High Complete Response Rate in Clinical Study of EO2463 for Indolent Non-Hodgkin Lymphoma at ASCO 2024. Retrieved May 31, 2024, from https://www.enterome.com/news-events/enterome-highlights-high-complete-response-rate-in-clinical-study-of-eo2463-for-indolent-non-hodgkin-lymphoma-at-asco-2024/[16] Pacylex Pharmaceuticals Reports Zelenirstat Phase 1 Safety and Efficacy Data at ASCO 2024. Retrieved May 31, 2024, from https://www.newsfilecorp.com/release/210409[17] Scholar Rock to Present New Data from SRK-181 Phase 1 DRAGON Trial at the American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved May 31, 2024, from https://www.businesswire.com/news/home/20240528070137/en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

免疫疗法临床申请临床2期临床结果临床1期

2024-05-24

·BioSpace

Pacylex Pharmaceuticals Reports Zelenirstat Phase 1 Safety and Efficacy Data at ASCO 2024

Edmonton, Alberta--(News - May 24, 2024) - Pacylex Pharmaceuticals Inc. (Pacylex) is a clinical-stage pharmaceutical company developing N-myristoyltransferase (NMT) inhibitors as targeted therapies for the treatment of hematologic cancers and solid tumors. Today Pacylex announced that complete Phase 1 clinical study results for zelenirstat, a proprietary, potent, NMTi, will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting from May 31 to June 4, 2024, at McCormick Place in Chicago, Illinois. To view the full announcement, including downloadable images, bios, and more, click here. Key Takeaways: Zelenirstat was well tolerated, and adverse events were primarily gastrointestinal side effects, most of which resolved spontaneously without dose reduction. Patients receiving the recommended Phase 2 dose of zelenirstat had significantly better progression free and overall survival than those treated at lower doses; 57% had stable disease or better for six months or longer, despite having 5 different types of cancer. Zelenirstat inhibits myristoylation of multiple oncogenic targets leading to the inhibition of the signaling of validated colon cancer targets EGFR and VEGFR. Click image above to view full announcement. About zelenirstat (PCLX-001) Zelenirstat (formerly identified as PCLX-001) is a first-in-class, oral, small molecule NMTi being developed to treat patients with leukemia, lymphoma, and solid tumors. Zelenirstat selectively killed cancer cells in vitro and in animal models has been shown to regress hematologic malignancies and inhibit the growth of lung and breast cancer tumors. In AML models, zelenirstat preferentially killed leukemic stem enriched cell populations and reduction of the leukemic burden directly in the bone marrow. About zelenirstat Phase 1 and 2 studies Pacylex completed the dose escalation phase of a Phase 1 multiple ascending dose safety, tolerability, and pharmacokinetics study on zelenirstat in people with relapsed/refractory lymphoma and refractory solid tumors (NCT04836195). A recommended Phase 2 dose was determined. Zelenirstat demonstrated an acceptable safety and tolerability profile, pharmacokinetics consistent with once daily oral dosing, and early signs of efficacy. Zelenirstat is currently being studied in a Phase 2a open-label study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of zelenirstat in patients with relapsed/refractory B-cell non-Hodgkin Lymphoma (NHL) and a separate Phase 2a cohort in patients with refractory metastatic colorectal cancer that has progressed despite all available standard therapies. About Pacylex Pharmaceuticals Pacylex is a clinical-stage pharmaceutical company headquartered in Edmonton, Alberta, Canada, targeting hematologic and solid cancers with orally bioavailable NMT inhibitors. Zelenirstat is the lead drug in a new class of NMT inhibitors, enabling Pacylex to exploit NMTs as new clinical targets for cancer treatment. Pacylex is conducting two multi-center Phase 2a studies in Canada in patients with relapsed/refractory NHL and refractory metastatic colorectal cancer. The IND for a Phase 1 multiple ascending dose study in acute myeloid leukemia (AML) has been cleared and the FDA has granted zelenirstat both Orphan Drug Designation and Fast Track Designation for AML. The US Department of Defense is supporting the initial clinical investigation of zelenirstat in patients with AML. The Cure Cancer Foundation supported initial clinical studies through its World's Longest Games. Forward-Looking Statements This press release contains forward-looking statements and forward-looking information within the meaning of applicable securities laws, such as statements relating to future events or the Company's future financial and operating performance, as well as the Company's business plans, growth initiatives, and objectives and prospects. Generally, forward-looking statements and forward-looking information may be identified by the use of forward-looking terminology, including the words "believe," "may," "will," "estimate," "continue," "anticipate," "intend," "should," "plan," "goal," "expect," "strategy," "future," "likely," "proposed," "scheduled," "forecast," "budget," "could," "would," variations of such words of phrases and other similar expressions, or by the use of words or phrases which state that certain actions, events or results may, could, would, or might occur or be achieved. However, the absence of these words does not mean that a statement is not forward looking. Forward-looking statements and forward-looking information are subject to numerous factors, risks and uncertainties that could cause actual results to differ materially, including, but not limited to, the Company's ability to successfully execute on its business plans and strategies, avoid delays in planned clinical trials, hire and retain key personnel, obtain appropriate or necessary governmental approvals to market potential products and obtain future funding for product development and working capital on commercially reasonable terms, changes in laws, and general macroeconomic conditions, including economic slowdowns, recessionary risks, rising inflation and interest rates, and supply chain disruptions. Forward-looking statements and forward-looking information are based on the beliefs of management as well as assumptions made by and information currently available to management as of the date hereof, and none of the Company or its affiliates undertakes any obligation to update or issue revisions to any forward-looking statements or forward-looking information contained herein to reflect any future events or circumstances, except as required by law. The foregoing does not constitute an offer or solicitation to acquire any securities in the Company or any related or associated entity or affiliate. The information contained herein is not intended as legal, tax, financial or investment advice. Furthermore, the information contained herein may not be applicable to or suitable for an individual's specific circumstances or needs. Contacts: Michael Weickert Ph.D 650-218-1840 michael.weickert@pacylex.com Source: Pacylex To view the source version of this press release, please visit

临床1期快速通道ASCO会议临床结果孤儿药

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

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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
结直肠癌	临床2期	-	Pacylex Pharmaceuticals, Inc.	-
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
非洲锥虫病	药物发现	英国	Wellcome Trust Clinical Research Facility	-
非洲锥虫病	药物发现	英国	University Of Dundee	-

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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 (ASCO2024) 人工标引	早期临床1期	B细胞淋巴瘤 \| 晚期恶性实体瘤	29	Zelenirstat	餘淵壓鏇繭鑰齋鏇膚選(鏇窪糧積艱顧繭窪廠範) = 糧鑰願範艱鬱窪膚製構鹹淵醖積築襯鏇鑰構壓 (繭淵憲顧淵築築膚餘鏇 ) 更多	积极	2024-05-24
AACR2024 人工标引	临床1期	实体瘤 \| 难治性B细胞淋巴瘤	28	Zelenirstat	醖鏇窪憲築積憲築鏇選(衊築顧襯鹹膚簾衊範獵) = 鬱鏇範鹽製製糧襯構選鏇夢艱糧網顧襯鑰構範 (窪淵醖選鹽範鑰窪簾觸 ) 更多	积极	2024-04-05
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	鬱憲艱遞願製構構蓋襯(廠築憲餘構壓鏇範鏇醖) = DLT was not observed up to and including the 210 mg/d cohort.Gastrointestinal DLTs were seen in the 280 mg/d cohort 蓋艱網遞觸網齋壓淵網 (鹽鏇鑰觸繭顧艱鑰選鏇 ) 更多	积极	2024-01-20
NCT04836195 (NEWS) 人工标引	临床1期	实体瘤 \| 淋巴瘤	29	Zelenirstat	衊願繭蓋襯繭憲夢醖憲(窪繭鏇憲範鏇糧糧網窪) = 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. 鬱鏇醖範簾網淵廠網鹹 (餘觸齋艱膚窪蓋積構築 ) 更多	积极	2023-11-30