Vodobatinib
(Synonyms: K0706) 目录号 : GC62103
Vodobatinib (K0706, SCO-088, SUN K706, SUN-K0706) is a novel BCR-ABL1 tyrosine kinase inhibitor with an IC50 of 7 nM. Vodobatinib exhibits activity against most BCR-ABL1 point mutants with IC50s of 167 nM, 154 nM,165 nM and 1967 nM for BCR-ABL1L248R, BCR-ABL1Y253H , BCR-ABL1E255V and BCR-ABL1T315I, respectively.
Cas No.:1388803-90-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Vodobatinib (K0706, SCO-088, SUN K706, SUN-K0706) is a novel BCR-ABL1 tyrosine kinase inhibitor with an IC50 of 7 nM. Vodobatinib exhibits activity against most BCR-ABL1 point mutants with IC50s of 167 nM, 154 nM,165 nM and 1967 nM for BCR-ABL1L248R, BCR-ABL1Y253H , BCR-ABL1E255V and BCR-ABL1T315I, respectively.
[1] Orlando Antelope, et al. Exp Hematol. 2019 Sep;77:36-40.e2.
| Cas No. | 1388803-90-4 | SDF | |
| 别名 | K0706 | ||
| 分子式 | C27H20ClN3O2 | 分子量 | 453.92 |
| 溶解度 | DMSO : 125 mg/mL (275.38 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.203 mL | 11.0152 mL | 22.0303 mL |
| 5 mM | 0.4406 mL | 2.203 mL | 4.4061 mL |
| 10 mM | 0.2203 mL | 1.1015 mL | 2.203 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
CML Resistant to 2nd-Generation TKIs: Mechanisms, Next Steps, and New Directions
Curr Hematol Malig Rep 2022 Dec;17(6):198-205.PMID:36264428DOI:10.1007/s11899-022-00683-3.
Purpose of review: The clinical scenario for chronic myeloid leukemia patients rapidly changed after the introduction of tyrosine kinase inhibitors (TKIs). Second-generation TKIs as frontline treatment increased the rate of deep molecular responses without increasing the rate of overall survival. About 20% of patients experience resistance to these agents, needing alternative treatments. Here, we reviewed the possible mechanisms of resistance, available treatment, and new drugs developed to counteract and overcome resistance. Recent findings: Results of novel TKIs have been recently reported, especially for the setting of T315I mutated patients, such as olverembatinib and asciminib, or for patients who developed resistance due to other mutations, such as Vodobatinib. Most of new TKIs are selected among compounds tested selective on ABL, therefore without possible off-target effects in the long term. New potential treatments are on the horizon in the field of CML, able to rescue patients treated firstly with one or more second-generation TKIs. Results of ongoing trials and real-world evidence dataset will help us to identify the appropriate timing of intervention and to select appropriate candidate to these drugs.
Plasma and cerebrospinal fluid pharmacokinetics of Vodobatinib, a neuroprotective c-Abl tyrosine kinase inhibitor for the treatment of Parkinson's disease
Parkinsonism Relat Disord 2023 Mar;108:105281.PMID:36717298DOI:10.1016/j.parkreldis.2023.105281.
Background: Preclinical 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. Objectives: To 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. Methods: Inhibition 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. Results: In 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 Cmax, 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. Cavg, 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. Conclusion: Based 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.
Management of Chronic Myeloid Leukemia Patients in Later Lines: The Role of Ponatinib and New Compounds
Clin Lymphoma Myeloma Leuk 2023 Mar 20;S2152-2650(23)00089-7.PMID:37029061DOI:10.1016/j.clml.2023.03.004.
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.