Valecobulin(Valecobulin) - 药物靶点：Tubulin_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

Tubulin

作用机制

微管蛋白抑制剂

治疗领域

肿瘤消化系统疾病

在研适应症-

非在研适应症

晚期结直肠腺癌晚期恶性实体瘤结直肠癌+ [1]

原研机构

Chong Kun Dang Pharmaceutical Corp.

在研机构-

非在研机构

Asan Medical Center

Chong Kun Dang Pharmaceutical Corp.

最高研发阶段终止临床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C26H28N6O5S

InChIKeyUKKRUIXIDCWALA-QFIPXVFZSA-N

CAS号1188371-47-2

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关联

5

项与 Valecobulin 相关的临床试验

NCT04696848 / Terminated临床1/2期IIT

A Phase I Study to Determine the Efficacy and Safety of CKD-516 Tablet Combined With Durvalumab(MEDI4736) in Patient Refractory Solid Tumors

This is a single center, open-label, nonrandomized, Phase 1b, dose-escalation study designed to determine maximum tolerated dose (MTD) of CKD-516 in combination with durvalumab and evaluate the safety and tolerability profile, efficacy of CKD-516 and durvalumab treatment.

开始日期2021-02-24

申办/合作机构

Asan Medical Center

NCT03076957 / Unknown status临床1/2期

A Phase 1/2a Study to Assess the Safety and Efficacy of CKD-516 Tab. in Combination With Irinotecan Inj. in Patients With Previously Treated Advanced Colorectal Cancer

The purpose of this open-label, dose-escalation phase I trial is to evaluate the safety, tolerability and pharmacokinetic profiles and to assess the efficacy of CKD-516 Tablet in Combination with Irinotecan inj. in Patients with Previously Treated Advanced Colorectal Cancer

开始日期2016-12-01

申办/合作机构

Chong Kun Dang Pharmaceutical Corp.

[+1]

NCT02300467 / Unknown status临床1期IIT

A Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of NOV120401 (CKD-516 Tablet) in Patients With Advanced Refractory Solid Tumors

The purpose of this open-label, dose-escalation phase I trial is to evaluate the safety, tolerability and pharmacokinetic profiles and to assess the efficacy of NOV120401 (CKD-516 Tablet), a novel vascular disrupting agent, in patients with advanced refractory solid tumors.

开始日期2014-12-01

申办/合作机构

National OncoVenture

[+1]

100 项与 Valecobulin 相关的临床结果

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100 项与 Valecobulin 相关的转化医学

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100 项与 Valecobulin 相关的专利（医药）

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16

项与 Valecobulin 相关的文献（医药）

2023-01-01·Toxicological Research

CKD-516 potentiates the anti-cancer activity of docetaxel against epidermal growth factor receptor tyrosine kinase inhibitor-resistant lung cancer

Article

作者: Kang, Keon Wook ; Park, Jaewoo ; Kim, Soo Jin ; Lee, Kyunghyeon ; Ryu, Keun Ho ; Kim, Se-Mi ; Park, Miso ; Kim, U Ji

Lung cancer is the leading cause of cancer death. Although docetaxel has been used as a second- or third-line treatment for non-small cell lung cancer (NSCLC), the objective response rate is less than 10%. Hence, there is a need to improve the clinical efficacy of docetaxel monotherapy; combination therapy should be considered. Here, we show that CKD-516, a vascular disruption agent, can be combined with docetaxel to treat epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-resistant NSCLC. CKD-516 was orally bioavailable; neither CKD-516 nor docetaxel affected the mean plasma concentration-time profile or pharmacokinetic parameters of the other drug. CKD-516 and docetaxel synergistically inhibited the growth of H1975 (with an L858R/T790M double mutation of EGFR) and A549 (with a KRAS mutation) lung cancer cell lines. In addition, docetaxel plus CKD-516 delayed tumor growth in-and extended the lifespan of-tumor-bearing mice. Thus, combination CKD-516 and docetaxel therapy could be used to treat EGFR-TKI-resistant NSCLC.

2021-10-01·Investigational New Drugs3区 · 医学

A phase 1 dose-escalation and dose-expansion study to assess the safety and efficacy of CKD-516, a novel vascular disrupting agent, in combination with Irinotecan in patients with previously treated metastatic colorectal cancer

3区 · 医学

Article

作者: Park, Young Suk ; Lim, Hyeong-Seok ; Han, Sae-Won ; Kim, Tae Won ; Kim, Tae-You ; Kim, Jeong Eun ; Shin, Sang Joon ; Jeong, Hyehyun ; Hong, Yong Sang ; Ahn, Joong Bae ; Kim, Seung Tae

Introduction The combination of an anti-angiogenic agent with cytotoxic chemotherapy is a standard treatment strategy for metastatic colorectal cancer. CKD-516 is an oral vascular disrupting agent that was preliminarily shown to be safe and efficacious as a monotherapy in refractory solid cancers. We evaluated the recommended phase 2 dose, safety, and preliminary efficacy of CKD-516 in combination with irinotecan in treatment-refractory metastatic colorectal cancer. Methods This phase 1 dose-escalation and dose-expansion study included patients with treatment-refractory metastatic colorectal cancer. CKD-516 tablets were administered for five consecutive days followed by two days off in combination with intravenous irinotecan (120 mg/m²) administered on day one of each treatment cycle every two weeks. A traditional 3 + 3 dose-escalation design was used. Results In total, 16 and 23 patients were enrolled in the dose-escalation and dose-expansion cohorts, respectively. The most common adverse events included diarrhea (79%), nausea (74%), vomiting (67%), and neutropenia (62%). No dose-limiting toxicity occurred, and the recommended phase 2 dose was determined at CKD-516/irinotecan doses of 11/120 mg/m². No cases of cardiac ischemia, cardiac dysfunction, or thromboembolism were reported. Among the 34 patients with available tumor response assessments, one patient achieved partial response (3%) and 26 patients achieved stable disease (76%). The median progression-free survival and overall survival were 4.1 and 11.6 months, respectively. Conclusion This phase 1 study showed that the combination of oral CKD-516 and irinotecan is safe and tolerable in metastatic, treatment-refractory colorectal patients and showed favorable efficacy outcomes. Further studies to confirm these preliminary findings are warranted. Trial registration number NCT03076957 (Registered at March 10, 2017).

2020-12-01·BMC Cancer2区 · 医学

Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft mouse model of lung squamous cell carcinoma

2区 · 医学

ArticleOA

作者: Jung, Chan Kwon ; Kang, Jin-Hyoung ; Kim, Yeon Sil ; Kim, Jeong-Oh ; Kim, Min-Young ; Shin, Jung-Young ; Son, Kyoung-Hwa

AbstractBackgroundHypoxic tumors are known to be highly resistant to radiotherapy and cause poor prognosis in non-small cell lung cancer (NSCLC) patients. CKD-516, a novel vascular disrupting agent (VDA), mainly affects blood vessels in the central area of the tumor and blocks tubulin polymerization, thereby destroying the aberrant tumor vasculature with a rapid decrease in blood, resulting in rapid tumor cell death. Therefore, we evaluated the anti-tumor efficacy of CKD-516 in combination with irradiation (IR) and examined tumor necrosis, delayed tumor growth, and expression of proteins involved in hypoxia and angiogenesis in this study.MethodsA xenograft mouse model of lung squamous cell carcinoma was established, and the tumor was exposed to IR 5 days per week. CKD-516 was administered with two treatment schedules (day 1 or days 1 and 5) 1 h after IR. After treatment, tumor tissues were stained with hematoxylin and eosin, and pimonidazole. HIF-1α, Glut-1, VEGF, CD31, and Ki-67 expression levels were evaluated using immunohistochemical staining.ResultsShort-term treatment with IR alone and CKD-516 + IR (d1) significantly reduced tumor volume (p = 0.006 andp = 0.048, respectively). Treatment with CKD-516 + IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p < 0.005). More specifically, CKD-516 + IR (d1) caused the most extensive tumor necrosis, which resulted in a significantly large hypoxic area (p = 0.02) and decreased HIF-1α, Glut-1, VEGF, and Ki-67 expression. Long-term administration of CKD-516 + IR reduced tumor volume and delayed tumor growth. This combination also greatly reduced the number of blood vessels (p = 0.0006) and significantly enhanced tumor necrosis (p = 0.004). CKD-516 + IR significantly increased HIF-1α expression (p = 0.0047), but significantly reduced VEGF expression (p = 0.0046).ConclusionsTaken together, our data show that when used in combination, CKD-516 and IR can significantly enhance anti-tumor efficacy compared to monotherapy in lung cancer xenograft mice.

100 项与 Valecobulin 相关的药物交易

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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
难治恶性实体肿瘤	临床2期	韩国	Asan Medical Center	2021-02-24
晚期结直肠腺癌	临床2期	韩国	Chong Kun Dang Pharmaceutical Corp.	2016-12-01
结直肠癌	临床2期	韩国	Chong Kun Dang Pharmaceutical Corp.	2016-12-01
结直肠癌	临床2期	韩国	Chong Kun Dang Pharmaceutical Corp.	2016-12-01
晚期恶性实体瘤	药物发现	韩国	Chong Kun Dang Pharmaceutical Corp.	2014-12-01

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临床结果

适应症

分期

评价

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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


NCT03076957 (Pubmed \| Invest New Drugs) 人工标引	临床1期	结直肠癌	39	Irinotecan+CKD-516	(鏇齋憲艱糧糧繭顧網壓) = CKD-516/irinotecan doses of 11/120 mg/m2 簾繭繭遞鹽鏇觸蓋鏇蓋 (襯簾願蓋壓餘顧鏇衊壓 ) 更多	积极	2021-10-01
NCT01028859 (Pubmed \| Cancer Res Treat) 人工标引	临床1期	HR阳性/HER2低表达实体瘤	23	CKD-516	(範簾鹽醖顧築鹹餘糧廠) = grade 3 hypertension 2/23 選糧鏇鬱積艱觸獵鹹膚 (蓋夢鑰糧憲獵積醖糧壓 ) 更多	积极	2016-01-01