A Phase 2b, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Three Different Doses of SCV 07 in Attenuating Oral Mucositis in Subjects With Head and Neck Cancer Receiving Concurrent Chemotherapy and Radiotherapy

This is a phase 2b, double-blind, placebo-controlled, 4-arm, adaptive-design trial, initially stratified by cisplatin regimen, and then randomized 1:1:1:1. The study will be conducted in subjects receiving ChemoRT for the treatment of squamous cell carcinomas (SCCs) of the oral cavity, oropharynx, hypopharynx, or larynx. The study includes a treatment period of approximately 7 weeks, depending on the subject's prescribed radiation plan, and Week 1 and Week 4 post RT follow-up visits. It also includes a longer follow-up period of approximately 12 months to determine if there is an effect of SCV 07 on the tumor response to ChemoRT.

开始日期2010-12-01

申办/合作机构

SciClone Pharmaceuticals LLC

NCT01310205 / CompletedN/A

An Extension of Study SCI-SCV-HCV-P2-001: Long-Term FU in Subj Who Opt for Retreatment With Pegylated Interferon and Ribavirin After Completing Treatment in a Phase 2 Study and Have Relapsed After at Least 44 Weeks Tx With Peg-IFN and RBV.

This is an extension of ongoing study SCI-SCV-HCV-P2-001 in which subjects will be invited to participate in this extension study if they complete treatment in study SCI-SCV-HCV-P2-001 and are eligible for retreatment with peg-IFN and RBV.

开始日期2010-08-01

申办/合作机构

SciClone Pharmaceuticals LLC

NCT00968357 / Completed临床2期

A Phase 2, Multicenter, Multidose, Open-Label Study to Evaluate the Safety and Immunomodulatory Effects of SCV-07 as Monotherapy or in Combination With Ribavirin in Noncirrhotic Subjects With Genotype 1 Chronic Hepatitis C Who Have Relapsed After a Response to a Course of at Least 44 Weeks Treatment With Pegylated Interferon and Ribavirin

SCV-07 (γ-D-glutamyl-L-tryptophan) is a new immunomodulatory compound that has been developed and patented both for composition and immunomodulatory use and is a synthetic dipeptide. The efficacy of SCV 07 in treating chronic hepatitis C virus (HCV) infection is expected to arise from the drug's ability to stimulate the T-helper 1 (Th1) type immune response and to block signal transducers and activator of transcription 3 (STAT3) mediated signaling. The purpose of this study is to determine if SCV-07 alone and/or SCV-07 in combination with ribavirin is safe and potentially effective for the treatment of genotype 1 compensated chronic hepatitis C in subjects who have relapsed after a response to a previous treatment course of at least 44 weeks with pegylated interferon and ribavirin. All subjects will receive 4 weeks of SCV-07 (Lead-in Phase), followed by 4 weeks of treatment with SCV-07 in combination with ribavirin (Combination Treatment).

开始日期2009-09-01

申办/合作机构

SciClone Pharmaceuticals LLC

100 项与戈洛莫德相关的临床结果

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100 项与戈洛莫德相关的转化医学

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100 项与戈洛莫德相关的专利（医药）

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项与戈洛莫德相关的文献（医药）

2020-08-12·Journal of biomolecular structure & dynamics

Identification and evaluation of glutathione conjugate gamma-l-glutamyl-l-cysteine for improved drug delivery to the brain

Article

作者: Samim, Mohammed ; Alajmi, Mohammed F. ; Ahmad, Farhan Jalees ; Hussain, Afzal ; Mohammad, Taj ; Hassan, Md. Imtaiyaz ; Jairajpuri, Deeba Shamim ; Rehman, Md Tabish ; Fatima, Saman

Glutathione (GU), an endogenous antioxidant tripeptide, is frequently transferred in the human brain through N-methyl-d-aspartate receptor (NMDAR), profusely expressed at the blood-brain barrier (BBB) junction. GU, also modifies the characteristics of tight junction proteins (occludin and claudin) at the site of BBB by depolarizing the enzyme, protein tyrosine phosphatase that manifests its usefulness for passive delivery of nanocarriers to the brain. GU, thus, represents itself as an ideal ligand for the surface decoration of nanocarriers to successfully administer them across the brain via receptor-mediated drug delivery pathway. Hence, we have employed here, in-silico approaches to identify the potential GU-like molecules, as appropriate ligand(s) for surface engineering of nanoconstruct with the purpose of attaining targeted drug delivery to the brain. Structure-based virtual screening methods was used to filter PubChem database for the identification of bioactive compounds with >95% structure similarity with GU. We have further screened the compounds against NMDAR using molecular docking approach. Top hits were selected based on their high binding affinities and selectivity towards NMDAR, and their binding pattern was analysed in detail. Finally, all atom molecular dynamics simulation for 100 ns was carried out on free NMDAR and in-presence of the selected GU-like compound, gamma-l-glutamyl-l-cysteine to evaluate complex stability and structural dynamics. In conclusion, gamma-l-glutamyl-l-cysteine may act as potential binding partner of NMDAR which can further be evaluated in drug delivery system to brain across the BBB.Communicated by Ramaswamy H. Sarma.

2020-01-01·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova

Therapy optimization of asthenic disorders in remissions in patients with paroxysmal-progressive schizophrenia (a clinical and immunological analysis)

Article

作者: Oleichik, I V ; Yakimets, A V ; Klyushnik, T P ; Zozulya, S A

OBJECTIVE:

To study the efficacy of the immunomodulatory drug γ-D-glutamyl-L-tryptophan in complex therapy of asthenic disorders in remissions in patients with schizophrenia and to analyze clinical and immunological indicators.

MATERIALS AND METHODS:

Sixty-three male patients (aged 41.9±9.46 years) with paroxysmal-progressive schizophrenia in remission (ICD-10 F20.x1; F20.x2), including 24 patients with affective-asthenic and 39 with negative-asthenic types, were studied. The assessment of the patients' condition was carried out using PANSS, SANS, CDSS, MFI-20. The activity of inflammatory markers: leukocyte elastase (LE) and α1-proteinase inhibitor (a1-PI) was determined in blood serum. The clinical and immunological assessment was performed before, after therapy (in 5 days) and at the remote stage (in a month).

RESULTS:

Augmentation of standard therapy with γ-D-glutamyl-L-tryptophan facilitated positive reduction in the main clinical manifestations of endogenous asthenia of both types in comparison with placebo (p<0.02). The features of the protease inhibitor system revealed in the patients confirm their clinical heterogeneity and also determine varying efficacy of augmentation by the immunotropic medicine. For patients with the low level of protease activity, which is characteristic of endogenous asthenia with prevalence of negative disorders in clinical picture, the augmentation by γ-D-glutamyl-L-tryptophan was more effective: the decrease in severity of asthenic symptoms was followed by the significant increase in the relatively reduced LE activity (p<0.01), which presumably, relates to the insufficiency of functional activity of neutrophils.

CONCLUSION:

Augmentation of complex therapy of asthenic disorders in schizophrenia by γ-D-glutamyl-L-tryptophan can be recommended.

2017-07-26·Journal of agricultural and food chemistry1区 · 农林科学

Intervention of Dietary Dipeptide Gamma-l-Glutamyl-l-Valine (γ-EV) Ameliorates Inflammatory Response in a Mouse Model of LPS-Induced Sepsis

1区 · 农林科学

Article

作者: Mine, Yoshinori ; Majumder, Kaustav ; Chee, MacKenzie E.

Sepsis, the systemic inflammatory response syndrome (SIRS) with infection is one of the leading causes of death in critically ill patients in the developed world due to the lack of effective antisepsis treatments. This study examined the efficacy of dietary dipeptide gamma-l-glutamyl-l-valine (γ-EV), which was characterized previously as an anti-inflammatory peptide, in an LPS-induced mouse model of sepsis. BALB/c mice were administered γ-EV via oral gavage followed by an intraperitoneal injection of LPS to induce sepsis. The γ-EV exhibited antisepsis activity by reducing the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in plasma and small intestine. γ-EV also reduced the phosphorylation of the signaling proteins JNK and IκBα. We concluded that γ-EV could possess an antisepsis effect against bacterial infection in intestine. This study proposes a signaling mechanism whereby the calcium-sensing receptor (CaSR) allosterically activated by γ-EV stimulates the interaction of β-arrestin2 with the TIR(TLR/IL-1R) signaling proteins TRAF6, TAB1, and IκBα to suppress inflammatory signaling.

项与戈洛莫德相关的新闻（医药）

2022-06-16

·药渡Daily

Kymera Therapeutics | STAT3和IRAKIMiD双料降解剂：KT-333和KT-413完成首例患者给药

2022年6月15日，Kymera Therapeutics宣布，分别用于评估STAT3降解剂KT-333和IRAKIMiD降解剂KT-413的I期临床研究已于近日完成首例患者给药。其中，KT-333临床试验的入组患者为复发性/难治性液体、实体肿瘤患者，包括T细胞淋巴瘤和白血病患者；KT-413临床试验正在招募复发性/难治性B细胞淋巴瘤患者入组，包括MYD88突变的弥漫性大B细胞淋巴瘤患者（DLBCL）。 “这些临床项目证明，在传统治疗模式无法有效解决的关键节点上，靶向蛋白降解剂展示它的优势潜力，为人类挑战癌症提供新的精准医疗解决方案”，Kymera Therapeutics联合创始人，总裁兼首席执行官Nello Mainolfi博士说，“这些临床研究患者给药环节的完成代表Kymera Therapeutics在认识这些首创在研药物的药理学和安全性方面取得了重要的进展，并且预计于今年下半年公布关于剂量递增临床研究的相关数据”。关于KT-333 STAT3是一个信号转导和转录激活因子，介导细胞对白介素、KITLG/SCF、LEP和其他生长因子的反应。一旦被激活，会将共激活剂（例如NCOA1或MED1）募集到目标基因的启动子区域。但STAT3长期被认为“不可成药”的蛋白靶点，已被证实与许多癌症、其他炎症和自身免疫性疾病有关。KT-333是靶向STAT3蛋白的一种有效的、选择性双官能团的小分子蛋白降解剂，用于多种肿瘤适应症。 KT-333研发进展来源：药渡数据库 I期临床研究将评估KT-333在复发性/难治性淋巴瘤和实体瘤成人患者中的安全性、耐受性、PK/PD和临床有效性（NCT05225584）。该项研究的第一阶段将进行KT-333的剂量递增试验；第二阶段将包括4个扩增队列，进一步表征KT-333在复发性和/或难治性外周T细胞淋巴瘤（PTCL）、皮肤T细胞淋巴瘤（CTCL）、大颗粒淋巴细胞白血病（LGL-L）和实体瘤患者中的安全性、耐受性、PK/PD和抗肿瘤活性。KT-333临床试验研究进展来源：药渡数据库 KT-333已于近期被美国FDA授予“孤儿药”资格认定，用于治疗外周T细胞淋巴瘤（PTCL）。众所周知，在美国一个新药一旦获得FDA孤儿药身份，将享有税收减免、免申请费、研发资助、加快审批以及上市后7年的市场独占权，甚至还可能获得优先审评资格。因此，从新药研发的角度看，以孤儿药身份进入市场，享受市场独占期后再拓展适应症，不失为一种“先走一步”的临床开发战略。关于KT-413 KT-413是正在开发的、有效的、选择性双官能团的小分子蛋白降解剂，用于MYD88突变的B细胞淋巴瘤，并且有潜质成为上述癌症的首选精准药物治疗方案。KT-413通过降解白细胞介素-1受体相关激酶4（IRAK4）和免疫调节药物（IMiD）底物Ikaros和Aiolos，从而抑制肿瘤细胞的复制。KT-413最初被开发用于复发性/难治性MYD88突变的DLBCL，并且有可能扩展到MYD88突变的其他适应症。KT-413研发进展来源：药渡数据库 I期临床研究将评估KT-413在复发性/难治性B细胞非霍奇金淋巴瘤成人患者中的安全性、耐受性、PK/PD（NCT05233033）。该项研究的第一阶段将进行KT-413的剂量递增试验；第二阶段将包括2个扩增队列，进一步表征KT-413在复发性/难治性MYD88突变和MYD88野生型的DLBCL。KT-413临床试验研究进展来源：药渡数据库 STAT3靶点的竞争格局 STAT3广泛存在于各类细胞和组织中，能够被多种细胞因子激活，在正常生理状态下，STAT3的活化快速而短暂，但在多种肿瘤细胞中，STAT3则被持续性激活并呈高表达水平，与肿瘤的发生发展密切相关，因此，针对STAT3靶点相关药物的竞争也非常激烈。目前已经上市的STAT3靶点药物是Verta的Golotimod。临床进展最快的是北京强新生物的Napabucasin和安德森癌症中心的Caffeic Acid，目前已经在中国开展III期临床研究；其次是贝勒医学院的C-188-9和天津尚德药缘的ACT-001，已经进入II期临床研究阶段，根据药渡数据调研，ACT-001作为1类新药，从2019年至今，已获得多项临床默示许可，适应症包括：视神经脊髓炎、儿童实体瘤、实体瘤脑转移、复发胶质母细胞瘤、晚期胶质瘤、进行性纤维化间质性肺病（包括特发性肺纤维化）。来源：药渡数据库针对STAT3靶点的相关药物还有很多正在进行临床试验，在此不一一例举，想了解更多详细信息，请登录”药渡数据“进行检索查询。参考来源Kymera Therapeutics官网、公告药渡数据库

蛋白降解靶向嵌合体孤儿药优先审批小分子药物

100 项与戈洛莫德相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D08928	-	A05A	DB05475

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
结核	俄罗斯	Verta, Inc.	2009-03-13
丙型肝炎	俄罗斯	-	2009-01-01
粘膜炎	俄罗斯	-	2009-01-01

未上市

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适应症	最高研发状态	国家/地区	公司	日期
慢性丙型肝炎基因型 1	临床2期	美国	SciClone Pharmaceuticals LLC	2009-09-01
头颈部肿瘤	临床2期	美国	SciClone Pharmaceuticals LLC	2008-09-01
口腔炎	临床2期	美国	SciClone Pharmaceuticals LLC	2008-09-01
哮喘	临床前	美国	SciClone Pharmaceuticals LLC	-
疱疹病毒感染	临床前	美国	SciClone Pharmaceuticals LLC	-
乳头状瘤病毒感染	临床前	美国	SciClone Pharmaceuticals LLC	-