SUN-K706(SUN-K706) - 药物靶点：Bcr-Abl_在研适应症：费城染色体阳性慢性粒细胞白血病，路易体病，慢性期慢性髓性白血病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Vodobatinib

+ [4]

靶点

Bcr-Abl

作用机制

Bcr-Abl抑制剂(bcr-abl酪氨酸激酶抑制剂)

治疗领域

肿瘤神经系统疾病内分泌与代谢疾病+ [2]

在研适应症

费城染色体阳性慢性粒细胞白血病路易体病慢性期慢性髓性白血病+ [2]

非在研适应症

帕金森病（青年型、早发型）

原研机构

Sun Pharma Advanced Research Co. Ltd.

在研机构

Sun Pharma Advanced Research Co. Ltd.

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (欧盟)

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结构

分子式C27H20ClN3O2

InChIKeyZQOBVMHBVWNVBG-UHFFFAOYSA-N

CAS号1388803-90-4

关联

8

项与 SUN-K706 相关的临床试验

EUCTR2018-003337-15-ES / Unknown status临床2期

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of K0706 in Subjects With Early Parkinson’s Disease

开始日期2019-10-17

申办/合作机构

Sun Pharma Advanced Research Company Ltd.

NCT03996460 / Recruiting临床2期IIT

A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of K0706 on Safety, Tolerability, Pharmacokinetics and Pharmacodynamics and Clinical Outcomes in Dementia With Lewy Bodies (DLB)

This study evaluates the safety and tolerability of treatment with K0706 in Dementia with Lewy Bodies (DLB).
The hypothesis is that K0706 will be safe and tolerable and that this drug will alter CSF and plasma biomarkers in DLB. Clinical assessments of cognitive, behavioral and motor functioning will also be evaluated. A total of 45 participants will be randomized 1:1:1 into 3 groups (n=15/per group) to be treated with sachet of 192 mg powder of K0706 ( equivalent to 96 mg capsule of K0706) or sachet of 384 mg powder of K0706 (equivalent to 192 capsule of K0706) or sachet of matching placebo ( equivalent to a capsule of placebo) for 12 weeks, followed by 4-week wash-out period.

开始日期2019-09-05

申办/合作机构

Georgetown University

[+1]

NCT03655236 / Terminated临床2期

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of K0706 in Subjects With Early Parkinson's Disease

This study consists of 2 parts. Part 1 of the study is conducted to evaluate the efficacy, safety, and tolerability of two doses of K0706 compared to placebo in subjects with early Parkinson's Disease who are not receiving dopaminergic therapy. Part 2 is an optional long term extension study for subjects who have completed week 40 of Part 1

开始日期2019-02-18

申办/合作机构

Sun Pharma Advanced Research Co. Ltd.

100 项与 SUN-K706 相关的临床结果

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100 项与 SUN-K706 相关的转化医学

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100 项与 SUN-K706 相关的专利（医药）

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6

项与 SUN-K706 相关的文献（医药）

2023-06-01·Clinical lymphoma, myeloma & leukemia

Management of Chronic Myeloid Leukemia Patients in Later Lines: The Role of Ponatinib and New Compounds.

Review

作者: Martelli, Maurizio ; Costa, Alessandro ; Scalzulli, Emilia ; Carmosino, Ida ; Breccia, Massimo ; Bisegna, Maria Laura

Limited therapeutic options and poor response probability still represent some unresolved issue in later lines chronic myeloid leukemia (CML) patients. In addition, sequential treatment is associated with reduced overall survival and may select new mutation, including the T315I, further reducing the therapeutic chances: outside the United States, ponatinib and allogenic stem cell transplant are the only available options. In the last decade, ponatinib improved outcomes in third-line patients, although limited by the risk of severe adverse occlusive events. Dose optimization strategies with lower doses of ponatinib in selected patients have shown to reduce toxicity while retaining efficacy, but higher doses are needed in T315I patients for an adequate disease control. Recently approved by FDA, the first-of-its-kind STAMP inhibitor asciminib has proven safe and effective, obtaining deep and stable molecular responses even in heavily pretreated patients and with T315I mutation. Unfortunately, a significant proportion of patients remain intolerant or refractory, making it crucial to develop new therapeutic options. Among these, novel agents such as vodobatinib and olverembatinib have provided promising result in clinical trials, representing valuable therapeutic possibilities in intolerant or refractory patients. Therefore, a more complex therapeutic paradigm is expected in the near future.

2023-03-01·Parkinsonism & Related Disorders

Plasma and cerebrospinal fluid pharmacokinetics of vodobatinib, a neuroprotective c-Abl tyrosine kinase inhibitor for the treatment of Parkinson's disease

Article

作者: Love, Damon ; Mandhane, Sanjay ; Damle, Nitin K ; Piccoli, Steven P ; Ramanathan, Vikram ; Hurko, Orest ; Talluri, Ravi S ; Yao, Siu-Long ; Walsh, Ryan R

BACKGROUNDPreclinical evidence suggests that c-Abl is critical in the pathogenesis of Parkinson's Disease (PD). Vodobatinib (K0706) is a potent, specific Abl kinase inhibitor currently being developed for the treatment of PD. In previously reported studies, nilotinib, a multikinase c-Abl inhibitor, did not show clinical activity as evidenced by no improvement of symptoms or the rate of decline after one to six months of treatment at the maximum permissible dose, presumably because of insufficient CNS penetration. Here we report clinical PK and safety data for vodobatinib.OBJECTIVESTo determine safety, plasma PK, and CSF penetration of vodobatinib in healthy volunteers and PD subjects following oral administration, and compare CSF levels to in vitro concentrations required for c-Abl inhibition relative to data reported for nilotinib.METHODSInhibition of c-Abl kinase activity and c-Abl binding affinity were first assessed in vitro. Healthy human volunteers and PD patients received various oral doses of vodobatinib once-daily for seven and fourteen days respectively, to assess safety, and plasma and CSF PK.RESULTSIn in vitro assays, vodobatinib was more potent (kinase IC₅₀ = 0.9 nM) than nilotinib (kinase IC₅₀ = 15-45 nM). Administration of vodobatinib 48, 192 and 384 mg to healthy subjects for 7 days yielded mean C_{max, CSF} values of 1.8, 11.6, and 12.2 nM respectively, with the two highest doses exceeding the IC₅₀ over the entire dosing interval. C_{avg, CSF} values were 6-8 times greater than the IC₅₀. Comparable CSF levels were observed in PD patients. All doses were well tolerated in both cohorts.CONCLUSIONBased on achieved CSF concentrations, the potential for c-Abl inhibition in the brain is substantially higher with vodobatinib than with nilotinib. The CSF PK profile of vodobatinib is suitable for determining if c-Abl inhibition will be neuroprotective in PD patients.

2023-03-01·Parkinsonism & Related Disorders

A novel brain penetrant c-Abl tyrosine kinase inhibitor: Paving a path forward to success in disease modification in Parkinson's disease

作者: Simuni, Tanya ; Merchant, Kalpana

A review.A review discussing novel brain penetrant c-abl tyrosine kinase inhibitor, paving a path forward to success in disease modification in Parkinson's disease.It also discusses vodobatinib appears to have better potency and greater central penetration than nilotinib.

100 项与 SUN-K706 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
费城染色体阳性急性淋巴细胞白血病	临床2期	西班牙	Sun Pharma Advanced Research Co. Ltd.	2016-06-27
费城染色体阳性急性淋巴细胞白血病	临床2期	印度	Sun Pharma Advanced Research Co. Ltd.	2016-06-27
费城染色体阳性急性淋巴细胞白血病	临床2期	英国	Sun Pharma Advanced Research Co. Ltd.	2016-06-27
费城染色体阳性急性淋巴细胞白血病	临床2期	韩国	Sun Pharma Advanced Research Co. Ltd.	2016-06-27
费城染色体阳性急性淋巴细胞白血病	临床2期	匈牙利	Sun Pharma Advanced Research Co. Ltd.	2016-06-27
费城染色体阳性急性淋巴细胞白血病	临床2期	土耳其	Sun Pharma Advanced Research Co. Ltd.	2016-06-27
费城染色体阳性急性淋巴细胞白血病	临床2期	意大利	Sun Pharma Advanced Research Co. Ltd.	2016-06-27
费城染色体阳性急性淋巴细胞白血病	临床2期	比利时	Sun Pharma Advanced Research Co. Ltd.	2016-06-27
费城染色体阳性急性淋巴细胞白血病	临床2期	罗马尼亚	Sun Pharma Advanced Research Co. Ltd.	2016-06-27
费城染色体阳性急性淋巴细胞白血病	临床2期	美国	Sun Pharma Advanced Research Co. Ltd.	2016-06-27

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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


NCT02629692 (ASH2021) 人工标引	临床1期	费城染色体阳性急性淋巴细胞白血病 \| 费城染色体阳性慢性粒细胞白血病末线 Philadelphia Chromosome Positive	52	vodobatinib (dose-escalation (DEs))	(鹹選築選蓋鹽鹹顧廠蓋) = Nineteen pts (37%) reported SAEs; vodobatinib related SAEs were reported in 3 pts (fatal intracranial haemorrhage (ICH), Grade 2 back pain and Grade 3 amnesia reported in 1 pt each) 獵壓壓積淵鹽廠選廠網 (衊糧顧顧獵遞廠蓋膚夢 ) 更多	积极	2021-11-05
				vodobatinib 174 mg (dose-expansion (DEx))