SPK-241(SPK-241) - 在研适应症：周围神经系统疾病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [1]

靶点-

作用机制

细胞凋亡诱导剂

治疗领域

神经系统疾病

在研适应症

周围神经系统疾病

非在研适应症

多发性骨髓瘤肿瘤神经痛

原研机构

Kirin Holdings Co., Ltd.

在研机构

Kirin Holdings Co., Ltd.

非在研机构

DARA Therapeutics, Inc.

Fortovia Therapeutics, Inc.初创企业

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C28H43N7O7

InChIKeyLQIPDFIUPOYMPR-BKYURJJWSA-N

CAS号151276-95-8

关联

3

项与 SPK-241 相关的临床试验

NCT00474916 / Completed临床2期

A Phase 2 Double-Blind Dose Escalation Study of KRN5500 for Neuropathic Pain in Patients With Cancer

The purpose of this study is to collect beginning information on whether intravenous (IV) administration of KRN5500 is safe and effective for treatment of neuropathic pain in patients with cancer.

开始日期2006-06-01

申办/合作机构

DARA Therapeutics, Inc.

NCT00017238 / Completed临床1期IIT

A Phase I Trial of KRN5500 (NSC 650426) Given as a 72 Hour Continuous IV Infusion Every 21 Days in Patients With Solid Tumors

Phase I trial to study the effectiveness of KRN5500 in treating patients who have solid tumors. Drugs used in chemotherapy, such as KRN5500, work in different ways to stop cancer cells from dividing so they stop growing or die

开始日期2002-02-01

申办/合作机构

National Cancer Institute

NCT00002923 / Completed临床1期IIT

Phase I Evaluation of KRN5500 (NSC650426)

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: Phase I trial to evaluate the effectiveness of KRN5500 in treating patients with metastatic solid tumors.

开始日期1997-05-01

申办/合作机构

Barbara Ann Karmanos Cancer Institute

[+1]

100 项与 SPK-241 相关的临床结果

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100 项与 SPK-241 相关的转化医学

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100 项与 SPK-241 相关的专利（医药）

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25

项与 SPK-241 相关的文献（医药）

2012-04-01·Journal of Pain and Symptom Management2区 · 医学

A Spicamycin Derivative (KRN5500) Provides Neuropathic Pain Relief in Patients With Advanced Cancer: A Placebo-Controlled, Proof-of-Concept Trial

2区 · 医学

Article

作者: Linda G. Jett ; Amy P. Abernethy ; Sharon M. Weinstein ; Isadore M. Pike ; Susan E. Spruill ; Andrea True Kelly

CONTEXTNeuropathic pain in patients with cancer can be difficult to treat effectively.OBJECTIVESThe purpose of the study was to determine safety and efficacy of KRN5500, a novel, spicamycin-derived, nonopioid analgesic agent, in patients with advanced cancer and neuropathic pain of any etiology.METHODSThe study was a Phase 2a, multicenter, double-blind, placebo-controlled, dose escalation clinical trial. Patients with refractory neuropathic pain and advanced cancer were randomly assigned 2:1 to receive a maximum of eight single escalating doses of KRN5500 or placebo, ranging from 0.6 to 2.2 mg/m(2). The primary objective was safety and tolerability. The secondary objective was efficacy, measured by change in average pain intensity on a 0-10 numeric rating scale administered one week after the patient's final dose.RESULTSNineteen patients received treatment (KRN5500 n=12; placebo n=7). The most frequently reported adverse events were gastrointestinal symptoms, which were more frequent and severe with KRN5500 than placebo; two (17%) KRN5500 patients discontinued the study because of nausea and vomiting. At study endpoint, KRN5500 exhibited a significant median decrease in pain intensity from baseline of 24% compared with 0% for placebo (P=0.03). The median for largest weekly reduction in target pain intensity was 29.5% for KRN5500 and 0% for placebo patients (P=0.02).CONCLUSIONThis proof-of-concept study for KRN5500 in patients with advanced cancer and any type of neuropathic pain found gastrointestinal adverse events to be the predominant safety concern. The results also provided the first indication of clinical and statistical efficacy in reducing pain intensity.

2011-11-01·British Journal of Haematology2区 · 医学

KRN5500, a spicamycin derivative, exerts anti‐myeloma effects through impairing both myeloma cells and osteoclasts

2区 · 医学

Article

作者: Watanabe, Keiichiro ; Yata, Ken‐ichiro ; Sakai, Akira ; Nakano, Ayako ; Oda, Asuka ; Kagawa, Kumiko ; Takeuchi, Kyoko ; Ikegame, Akishige ; Cui, Qu ; Nakamura, Shingen ; Miki, Hirokazu ; Amou, Hiroe ; Ozaki, Shuji ; Hiasa, Masahiro ; Harada, Takeshi ; Fujii, Shiro ; Matsumoto, Toshio ; Abe, Masahiro

SummaryThe spicamycin analogue KRN5500 alters glycoprotein processing and induces damage in the endoplasmic reticulum (ER)‐Golgi apparatus in cancer cells. In the present study, we explored the cytotoxic effects of KRN5500 on multiple myeloma (MM) cells and the bone marrow microenvironment with special reference to ER stress. Cell proliferation assay showed that KRN5500 induced G1 arrest and apoptosis in MM cells in a time‐ and dose‐dependent manner. KRN5500 enhanced ER stress independently of caspase activation in MM cells. This cell death was observed even in the presence of bone marrow stroma cells or osteoclasts. Notably, KRN5500 induced cell death also in osteoclasts. In vivo effects of KRN5500 were evaluated using two xenograft models established in severe combined immunodeficient (SCID) mice by either subcutaneous injection of RPMI 8226 cells or intra‐bone injection of INA‐6 cells to subcutaneously implanted rabbit bones (SCID‐rab model). KRN5500 significantly inhibited tumour growth in both animal models, and decreased the number of osteoclasts, which resulted in prevention of bone destruction in the SCID‐rab model. These results suggest that KRN5500 exerts anti‐MM effects through impairing both MM cells and osteoclasts. Therefore, this unique mechanism of KRN5500 might be a useful therapeutic option in patients with MM.

2006-02-01·Nihon rinsho. Japanese journal of clinical medicine

[Spicamycin derivative].

Review

作者: Mizumura, Yasuo

Spicamycin, induced differentiation of human myeloid leukemia cells (HL-60), is found to show a potent antitumor activity by inhibiting protein synthesis. Among the various semisynthetic derivatives of spicamycin, KRN5500 showed a marked efficacy in human tumor xenograft model. KRN5500 itself has, however, only minor inhibitory effects on protein synthesis in cell free system. A metabolite, SAN-Gly, which is thought to be generated through metabolism of KRN5500 by a cytosomal enzyme, exhibited a marked inhibitory effect. KRN5500 is expected to be useful even for treatment of refractory solid tumors because of its unique antitumor mechanism. A phase I clinical trials underwent at the National Cancer Center Hospital in Tokyo and at the National Cancer Institute in the USA. Unfortunately, the drug toxicities in addition to grade 4 pulmonary disorders were occurred, partly caused by the organic solvents and chemical essential for its dissolution. To overcome such a severe adverse effects, we conducted to examine whether incorporation of KRN5500 into polymeric micelles (KRN/m) could reduce a pulmonary disorder using a bleomycin (BLM)-induced lung injury rat model or exhibit antitumor activity similar to KRN5500. In conclusion, this study demonstrated that KRN/m is superior to KRN5500 because the pulmonary toxicity was reduced and the potent antitumor activity of KRN5500 was retained after the incorporation of KRN5500 into micelles. We think that these results justify a clinical phase I trial of KRN/m.

100 项与 SPK-241 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15215

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
神经痛	临床2期	波多黎各	DARA Therapeutics, Inc.	2006-06-01
多发性骨髓瘤	临床2期	美国	Fortovia Therapeutics, Inc.初创企业	-
周围神经系统疾病	临床2期	-	Kirin Holdings Co., Ltd.	-
肿瘤	药物发现	波多黎各	DARA Therapeutics, Inc.	2006-06-01
肿瘤	药物发现	美国	DARA Therapeutics, Inc.	2006-06-01
神经痛	药物发现	美国	DARA Therapeutics, Inc.	2006-06-01