Avanbulin
(Synonyms: BAL27862) 目录号 : GC63663
Avanbulin (BAL27862) 是一种有效的秋水仙碱位点结合的微管蛋白 (tubulin) 装配抑制剂。Avanbulin 在 37 °C 抑制微管蛋白组装 (IC50=1.4 μM)。Avanbulin 与微管蛋白结合的 Kd 值为 244 nM。Avanbulin 可用于癌症和细胞分裂的研究。
Cas No.:798577-91-0
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
Avanbulin (BAL27862) is a potent, Colchicine site-binding, tubulin assembly inhibitor. Avanbulin inhibits tubulin assembly at 37 °C with an IC50 of 1.4 μM. Avanbulin binds to tubulin with an apparent Kd value of 244 nM. Avanbulin can be used for the research of cancer and cell division[1][2][3][4].
Avanbulin (0-4 μM) binds to tubulin with an apparent Kd value of 244 nM[1].Avanbulin (0-20 μM) and Colchicine (0-10 μM) are competitive for binding to tubulin with an apparent Ki value of 1.8 μM[1].Avanbulin binds to the same site as Colchicine at the intradimer interface[1].Avanbulin (50 μM; 0, 10, 20, 30, 60 min) induces the proteolysis of tubulin[1].Avanbulin (1-100 nM; 72 h; HeLa-tubGFP cells) has anti-proliferative effects[1].Avanbulin (33 nM; 0, 10, 20, 30, 60 min; HeLa-tubGFP cells) collapses the mitotic spindle and forms the tiny tubulin aggregates[1].Avanbulin does not induce the formation of tubulin oligomers[1].Avanbulin (0.1 nM-1.0 μM; 96 hours) induces growth inhibition of cells with a median relative IC50 of 13.8 nM[2].Avanbulin (0-1,000 nM; 3 days) inhibits the growth of glioblastoma cancer stem-like cells, GBM6 (EC50=20.8 nM) and GBM9 (EC50=21.7 nM) [3].Avanbulin (6 nM and 20 nM) inhibits the migration of GBM6 and GBM9 cells[3].Avanbulin (6 nM and 20 nM; GBM6-shEB1 and GBM6-sh0 cells) triggers astrocytic differentiation of GBM6 in an EB1-dependent manner[3].Avanbulin (12 nM; 4 h) reduces kinetochore-microtubule (KT-MT) occupancy of MG132(10 μM; 2h) treated hTert-RPE1 eGFP-α-tubulin cells[4].Avanbulin (12 nM; 4 h) reduces average inter-KT distances of cells[4].Avanbulin-treated (12 nM; 4 h) cells show intact spindle morphology and lack of obvious chromosome alignment defects[4].
[1]. Prota AE, et al. The novel microtubule-destabilizing drug avanbulin binds to the colchicine site of tubulin with distinct effects on microtubule organization. J Mol Biol. 2014 Apr 17;426(8):1848-60.
[2]. Kolb EA, et al. Initial testing (stage 1) of BAL101553, a novel tubulin binding agent, by the pediatric preclinical testing program. Pediatr Blood Cancer. 2015 Jun;62(6):1106-9.
[3]. BergÈs R, et al. The Novel Tubulin-Binding Checkpoint Activator BAL101553 Inhibits EB1-Dependent Migration and Invasion and Promotes Differentiation of Glioblastoma Stem-like Cells. Mol Cancer Ther. 2016 Nov;15(11):2740-2749.
[4]. Dudka D, et al. Complete microtubule-kinetochore occupancy favours the segregation of merotelic attachments. Nat Commun. 2018;9(1):2042. Published 2018 May 23.
| Cas No. | 798577-91-0 | SDF | |
| 别名 | BAL27862 | ||
| 分子式 | C20H17N7O2 | 分子量 | 387.39 |
| 溶解度 | DMSO : 250 mg/mL (645.34 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 | 2.5814 mL | 12.9069 mL | 25.8138 mL |
| 5 mM | 0.5163 mL | 2.5814 mL | 5.1628 mL |
| 10 mM | 0.2581 mL | 1.2907 mL | 2.5814 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。
Phase 1/2a trial of intravenous BAL101553, a novel controller of the spindle assembly checkpoint, in advanced solid tumours
Br J Cancer 2020 Oct;123(9):1360-1369.PMID:32741975DOI:10.1038/s41416-020-1010-8.
Background: BAL101553 (lisavanbulin), the lysine prodrug of BAL27862 (Avanbulin), exhibits broad anti-proliferative activity in human cancer models refractory to clinically relevant microtubule-targeting agents. Methods: This two-part, open-label, phase 1/2a study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of 2-h infusion of BAL101553 in adults with advanced or recurrent solid tumours. The MTD was determined using a modified accelerated titration design in phase I. Patients received BAL101553 at the MTD and at lower doses in the phase 2a expansion to characterise safety and efficacy and to determine the recommended phase 2 dose (RP2D). Results: Seventy-three patients received BAL101553 at doses of 15-80 mg/m2 (phase 1, n = 24; phase 2a, n = 49). The MTD was 60 mg/m2; DLTs observed at doses ≥60 mg/m2 were reversible Grade 2-3 gait disturbance with Grade 2 peripheral sensory neuropathy. In phase 2a, asymptomatic myocardial injury was observed at doses ≥45 mg/m2. The RP2D for 2-h intravenous infusion was 30 mg/m2. The overall disease control rate was 26.3% in the efficacy population. Conclusions: The RP2D for 2-h infusion of BAL101553 was well tolerated. Dose-limiting neurological and myocardial side effects were consistent with the agent's vascular-disrupting properties. Clinical trial registration: EudraCT: 2010-024237-23.
Safety and anti-tumor activity of lisavanbulin administered as 48-hour infusion in patients with ovarian cancer or recurrent glioblastoma: a phase 2a study
Invest New Drugs 2023 Feb 16.PMID:36792805DOI:10.1007/s10637-023-01336-9.
Lisavanbulin (BAL101553) is the prodrug of Avanbulin (BAL27862), a microtubule-destabilizing agent. The goal of this study (NCT02895360) was to characterize the safety, tolerability and antitumor activity of lisavanbulin administered as a 48-hour intravenous (IV) infusion at the recommended Phase 2 dose (RP2D) of 70 mg/m2. Results from the Phase 1 dose-escalation portion of the study identifying the RP2D have been previously reported. Here, we present the findings from the Phase 2a portion of this study. Methods. This multi-center, open-label study included patients with ovarian, fallopian-tube, or primary peritoneal cancer that was either platinum-resistant or refractory (11 patients), or with first recurrence of glioblastoma (12 patients). Lisavanbulin was administered as a 48-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle. Results. Lisavanbulin was well tolerated in both patient cohorts. Thirteen patients (56.5%) developed 49 adverse events assessed as related to study treatment. The majority were mild or moderate; four were grade 3/4. Sixteen SAEs were reported in nine patients (39.1%), with none considered related to study treatment. No AEs led to permanent treatment discontinuation. Three patients in the ovarian cancer cohort had stable disease with lesion size reductions after two cycles of treatment; in the glioblastoma cohort, one patient showed partial response with a > 90% glioblastoma area reduction as best response, and one patient had stable disease after eight cycles of treatment. Conclusion. This study demonstrated a favorable safety and tolerability profile of 48-hour continuous IV infusion of lisavanbulin in patients with solid extracranial tumors or glioblastoma. Clinicaltrials.gov registration: NCT02895360.