规格 | 价格 | 库存 | 数量 |
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10 mM * 1 mL in DMSO |
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1mg |
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25mg |
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50mg |
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1g |
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靶点 |
Bcl-2 (Ki = 0.01 nM); Bcl-xL (Ki = 48 nM); Bcl-W (Ki = 245 nM)
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体外研究 (In Vitro) |
ABT-199 对 Bcl-xL、Mcl-1 和 Bcl-w 的敏感性较低,Ki 分别为 48 nM、> 444 nM 和 245 nM。 ABT-199 对 FL5.12-Bcl-xL 细胞表现出弱活性,EC50 为 261 nM,但有效抑制 FL5.12-Bcl-2 细胞、RS4;11 细胞,EC50 为 4 nM 和 8 nM。在 RS4;11 细胞中,ABT-199 引起快速细胞凋亡,并伴有细胞色素 c 的释放、半胱天冬酶的激活、磷脂酰丝氨酸的外化以及亚 G0/G1 DNA 的积累。根据定量免疫印迹,NHL、DLBCL、MCL、AML 和 ALL 细胞系中的 Bcl-2 表达与 ABT-199 敏感性密切相关。 ABT-199 诱导 CLL 细胞凋亡的平均 EC50 为 3.0 nM。 [1]
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体内研究 (In Vivo) |
ABT-199 (100 mg/kg) 在 RS4;11 异种移植物中引起最大 95% 的肿瘤生长抑制和 152% 的肿瘤生长延迟。 ABT-199 可单独使用或与其他药物(例如 SDX-105)联合使用,以抑制异种移植物的生长(DoHH2、Granta-519)。 [1]
在这里,我们报道了navitoclax的重组,以获得一种高效,口服生物利用和bcl -2选择性抑制剂ABT-199。该化合物在体内抑制bcl -2依赖性肿瘤的生长,并保护人类血小板。单剂量ABT-199治疗3例难治性慢性淋巴细胞白血病患者,24小时内肿瘤溶解[2] 。 为了在更类似于潜在临床应用的情况下研究VEN (Venetoclax)在个体白血病样本中的抗白血病活性,我们在不同个体、患者来源的小鼠异种移植ALL样本(N = 12)的临床前ii期样试验中研究了其抗白血病活性。移植到受体小鼠身上3周后,携带all的动物用VEN治疗10天,比较VEN (Venetoclax)或载药治疗后每一种白血病复发的次数。我们观察到VEN明显的体内抗白血病活性,这是由生存时间(“δ生存期”)的差异所表明的,从最小的影响到超过140天无ALL表现的延长生存期(图3a)。这种体内反应的变化与体外观察到的VEN敏感性的异质性相似,体外分析的EC50值显示与体内生存时间有中等程度的关联[3] 。 在出现白血病表现(受体外周血中存在5%的人ALL细胞)后,用VEN (Venetoclax)或载药治疗小鼠10天,然后评估无白血病生存,直到每个受体出现疾病表现。从更大的生物重复组中获得的这些结果精确地反映了临床前试验中看到的药物反应,重要的是,它清楚地对应于线粒体启动评估的BCL-2依赖程度:(i) PDX13显示出轻微的疾病表现延迟和低BCL-2依赖(图1)。3f,3f,平均生存差2.3天,BAD-HRK启动率18.6%),(ii)在PDX10中,我们观察到VEN治疗后明显延迟了显性白血病的发作,与明确的BCL-2依赖性一致(图。3g,3g,平均生存差43.2天,BAD-HRK启动率56.8%),(iii) VEN (Venetoclax)组在观察期内无白血病表现的PDX2生存期延长(图2)。3h,3h,超过70天生存时间优越,BAD-HRK启动率80.3%),对应于BCL-2的强依赖性。[3] |
酶活实验 |
ABT-199 对 Bcl-2 家族不同亚型的结合亲和力(Ki 或 IC50)通过竞争性荧光偏振测定来确定。使用的肽探针和蛋白质对如下::f-bad (1 nM) 和 Bcl-xL (6 nM)、f-Bax (1 nM) 和 Bcl-2 (10 nM)、f-Bax (1 nM) ) 和 Bcl-w (40 nM)、f-Noxa (2 nM) 和 Mcl-1 (40 nM)、f-Bax (1 nM) 和 Bcl-2-A1 (15 nM)。时间分辨荧光共振能量转移测定也用于确定 Bcl-xL 的结合亲和力。在室温下,将 Bcl-xL(1 nM,His 标记)、200 nM f-Bak、1 nM Tb 标记的抗 His 抗体和 ABT-199 混合 30 分钟。
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细胞实验 |
RS4;11细胞在96孔板上以5 × 104 /孔的密度接种后,用ABT-199 (Venetoclax)稀释半对数步处理,从1 μM-0.05 nM开始。ABT-199 (Venetoclax)与白血病和淋巴瘤细胞系一起孵育48小时,每孔1.5-2 × 104个细胞。使用Cell TiterGlo试剂,评估对增殖的影响。使用非线性回归分析浓度-响应数据以确定EC50值[1]。
来自T-ALL细胞系的细胞(补充表1,可在Blood网站上获得)以每孔10万个细胞的速度在96孔板中进行镀。细胞在100µL含10%胎牛血清的培养基中孵育48小时,其中加入5µL适当的ABT-199 (Venetoclax)稀释剂或二甲亚砜(DMSO)。[2] 在添加20% FCS和1% l-谷氨酰胺的RPMI 1640中培养细胞,进行细胞活力测定。将细胞暴露于11种不同浓度的VEN (Venetoclax) (0.1 nM、1 nM、10 nM、50 nM、100 nM、250 nM、500 nM、1µM、3µM、5µM和10µM)中72 h (BCP-ALL细胞系)或24 h (BCP-ALL PDX细胞)。[3] |
动物实验 |
Mice: Nonobese diabetic/severe combined immunodeficient γ (NSG) mice are given a 150 µL injection of phosphate-buffered saline containing 5×106 luciferase-labeled LOUCY cells at the age of 6 weeks in the tail vein.
The IVIS Lumina II imaging system measures the bioluminescence at regular intervals. After the cells have engrafted and the mice have been randomly split into two groups at 6 weeks (each group contains an equal number of males and females), the treatment is initiated on day 0 of the experiment. Venetoclax (ABT-199) 100 mg/kg body weight or vehicle is administered orally to mice for 4 days in a row. Days 0, 2, and 4 are used to measure the bioluminescene.[1]
Nonobese diabetic/severe combined immunodeficient γ (NSG) mice were injected at 6 weeks of age in the tail vein with 150 µL phosphate-buffered saline containing 5 × 106 luciferase-labeled LOUCY cells. At regular time points, the bioluminescence was measured using the IVIS Lumina II imaging system. At 6 weeks, the cells were engrafted and the mice were randomly divided into 2 groups (with an equal number of males and females in both groups), and the treatment was started on day 0. Mice were treated with 100 mg ABT-199/kg body weight or with vehicle via oral gavage for 4 consecutive days. Venetoclax (ABT-199) was formulated in 60% phosal 50 propylene glycol, 30% polyethylene glycol 400, and 10% ethanol. At days 0, 2, and 4 the bioluminescene was measured. Before imaging, the mice were injected intraperitoneally with 200 µL of a 15 mg/mL firefly d-luciferin potassium salt solution and anesthetized by inhalation of 5% isoflurane. The mice were imaged 10 minutes after luciferin injection. The total bioluminescence signal in each mouse was calculated via the region of interest tool (total counts) in the Living Image software.[2] A xenograft of primary human T-ALL cells from patient 3 was established in NSG mice by retro-orbital injection. Upon establishment of disease, human leukemic cells were isolated from the spleen and retransplanted into secondary recipients. Next, tertiary xenograft injections were performed in a cohort of 10 NSG mice and leukemia engraftment was monitored by human CD45 staining in peripheral blood using FACS analysis with the S3 cell sorter. Upon detection of human CD45+ leukemic blasts in peripheral blood, mice were randomized in 2 groups and treated with vehicle or 100 mg Venetoclax (ABT-199)/kg body weight for 7 consecutive days. After treatment, animals were sacrificed and the percentage human CD45-positive leukemic blasts in bone marrow were determined by FACS as described above.[2] Upon transplantation of ALL cells, engraftment of human blasts was monitored in peripheral blood by flow cytometry surface staining for huCD19 and huCD4549,50. Mice were treated with vehicle (60% Phosal 50 PG, 30% polyethylene glycol and 10% ethanol) or VEN (Venetoclax) 100 mg/kg/day orally for 10 days. Treatment was initiated on day 21 post transplantation (Fig. (Fig.3a)3a) or upon engraftment of more than 5% blasts in the peripheral blood (Fig. 3f–h). Posttreatment survival times were defined as manifestation of clinically overt leukemia in recipient animals upon initiation of treatment. Manifestation of leukemia was confirmed by flow cytometry staining of bone marrow and spleen cells as described above showing high percentages of human ALL in the respective compartments. For the independent cohort (Fig. (Fig.4)4) treatment was carried out as previously described.[3] |
参考文献 |
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其他信息 |
Venetoclax is a member of the class of pyrrolopyridines that is a potent inhibitor of the antiapoptotic protein B-cell lymphoma 2. It is used for treamtment of chronic lymphocytic leukemia with 17p deletion. It has a role as an apoptosis inducer, an antineoplastic agent and a B-cell lymphoma 2 inhibitor. It is a member of oxanes, a N-sulfonylcarboxamide, an aromatic ether, a pyrrolopyridine, a member of monochlorobenzenes, a N-arylpiperazine, a N-alkylpiperazine and a C-nitro compound.
Venetoclax is a BCL-2 inhibitor that was initially approved by the FDA in April 2016. Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are important regulators of the apoptotic (programmed cell death) process,. Venetoclax is used to treat chronic lymphocytic leukemia (CLL) and certain types of small lymphocytic lymphoma. CLL is the most prevalent leukemia diagnosed in Western countries. Venetoclax was developed through reverse engineering of the BCL-2 protein family inhibitor, navitoclax. Venetoclax is approximately 10 times more potent than navitoclax with regard to induction of apoptosis in CLL cells. A new indication was approved in 2018 for the treatment patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy. Previously, this drug was indicated only for patients with 17p gene deletion. Venetoclax is a BCL-2 Inhibitor. The mechanism of action of venetoclax is as a P-Glycoprotein Inhibitor. The physiologic effect of venetoclax is by means of Increased Cellular Death. Venetoclax is an oral selective BCL-2 inhibitor and antineoplastic agent used in the therapy of refractory chronic lymphocytic leukemia (CLL). Venetoclax is associated with a low rate of transient serum enzyme elevations during therapy, but has not been implicated in cases of clinically apparent acute liver injury with jaundice. Venetoclax has potent immunosuppressive activity and may be capable of causing reactivation of hepatitis B. View MoreVenetoclax is an orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. Venetoclax mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells. Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis; its expression is associated with increased drug resistance and tumor cell survival. Compared to the Bcl-2 inhibitor navitoclax, this agent does not inhibit bcl-XL and does not cause bcl-XL-mediated thrombocytopenia. Drug Indication Venetoclax is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). It is also used in combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. Venclyxto in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) (see section 5. 1). Venclyxto in combination with rituximab is indicated for the treatment of adult patients with CLL who have received at least one prior therapy. Venclyxto monotherapy is indicated for the treatment of CLL: - in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B cell receptor pathway inhibitor, or- in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor. Venclyxto in combination with a hypomethylating agent is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy. Pharmacodynamics Venetoclax induces rapid and potent onset apoptosis of CLL cells, powerful enough to act within 24h and to lead to tumor lysis syndrome,,. Selective targeting of BCL2 with venetoclax has demonstrated a manageable safety profile and has been shown to induce significant response in patients with relapsed CLL (chronic lymphocytic leukemia) or SLL (small lymphocytic leukemia), including patients with poor prognostic features. This drug is not expected to have a significant impact on the cardiac QT interval. Venetoclax has demonstrated efficacy in various types of lymphoid malignancies, including relapsed/ refractory CLL harboring deletion 17p, with an overall response rate of approximately 80%. Absorption Following several oral administrations after a meal, the maximum plasma concentration of venetoclax was reached 5-8 hours after the dose. Venetoclax steady state AUC (area under the curve) increased proportionally over the dose range of 150-800 mg. After a low-fat meal, venetoclax mean (± standard deviation) steady-state Cmax was 2.1 ± 1.1 μg/mL and AUC0-24 was 32.8 ± 16.9 μg•h/mL at the 400 mg once daily dose. When compared with the fasted state, venetoclax exposure increased by 3.4 times when ingested with a low-fat meal and 5.2 times with a high-fat meal. When comparing low versus high fat, the Cmax and AUC were both increased by 50% when ingested with a high-fat meal. The FDA label indicataes that venetoclax should be taken with food,. Route of Elimination After single oral administration of 200 mg radiolabeled [14C]-venetoclax dose to healthy subjects, >99.9% of the dose was found in feces and <0.1% of the dose was excreted in urine within 9 days, suggesting that hepatic elimination is responsible for the clearance of venetoclax from systemic circulation. Unchanged venetoclax accounted for 20.8% of the radioactive dose excreted in feces. Volume of Distribution The population estimate for apparent volume of distribution (Vdss/F) of venetoclax ranged from 256-321 L. Clearance Mainly hepatic. Metabolism / Metabolites In vitro studies demonstrated that venetoclax is predominantly metabolized as a substrate of CYP3A4/5,,. DrugBank Biological Half-Life The half-life of venetoclax is reported to be 19-26 hours, after administration of a single 50-mg dose,. Mechanism of Action Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are necessary regulators of the apoptotic (anti-cell programmed death) process. This family comprises proapoptotic and prosurvival proteins for various cells. Cancer cells evade apoptosis by inhibiting programmed cell death (apoptosis). The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2-like 1 (BCL-X(L)), which has demonstrated clinical efficacy in some BCL-2-dependent hematological cancers. Selective inhibition of BCL-2 by venetoclax, sparing BCL-xL enables therapeutic induction of apoptosis without the negative effect of thrombocytopenia,. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins, leading to mitochondrial outer membrane permeabilization and the activation of caspase enzymes. In nonclinical studies, venetoclax has shown cytotoxic activity in tumor cells that overexpress BCL-2. Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are key regulators of the apoptotic process. This family comprises proapoptotic and prosurvival proteins, and shifting the balance toward the latter is an established mechanism whereby cancer cells evade apoptosis. The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2-like 1 (BCL-X(L)), which has shown clinical efficacy in some BCL-2-dependent hematological cancers. However, concomitant on-target thrombocytopenia caused by BCL-X(L) inhibition limits the efficacy achievable with this agent. Here we report the re-engineering of navitoclax to create a highly potent, orally bioavailable and BCL-2-selective inhibitor, ABT-199. This compound inhibits the growth of BCL-2-dependent tumors in vivo and spares human platelets. A single dose of ABT-199 in three patients with refractory chronic lymphocytic leukemia resulted in tumor lysis within 24 h. These data indicate that selective pharmacological inhibition of BCL-2 shows promise for the treatment of BCL-2-dependent hematological cancers.[1] T-cell acute lymphoblastic leukemia (T-ALL) is a high-risk subtype of acute lymphoblastic leukemia (ALL) with gradually improved survival through introduction of intensified chemotherapy. However, therapy-resistant or refractory T-ALL remains a major clinical challenge. Here, we evaluated B-cell lymphoma (BCL)-2 inhibition by the BH3 mimetic ABT-199 as a new therapeutic strategy in human T-ALL. The T-ALL cell line LOUCY, which shows a transcriptional program related to immature T-ALL, exhibited high in vitro and in vivo sensitivity for ABT-199 in correspondence with high levels of BCL-2. In addition, ABT-199 showed synergistic therapeutic effects with different chemotherapeutic agents including doxorubicin, l-asparaginase, and dexamethasone. Furthermore, in vitro analysis of primary patient samples indicated that some immature, TLX3- or HOXA-positive primary T-ALLs are highly sensitive to BCL-2 inhibition, whereas TAL1 driven tumors mostly showed poor ABT-199 responses. Because BCL-2 shows high expression in early T-cell precursors and gradually decreases during normal T-cell differentiation, differences in ABT-199 sensitivity could partially be mediated by distinct stages of differentiation arrest between different molecular genetic subtypes of human T-ALL. In conclusion, our study highlights BCL-2 as an attractive molecular target in specific subtypes of human T-ALL that could be exploited by ABT-199.[2] Deregulated cell death pathways contribute to leukemogenesis and treatment failure in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Intrinsic apoptosis signaling is regulated by different proapoptotic and antiapoptotic molecules: proapoptotic BCL-2 homology domain 3 (BH3) proteins activate prodeath molecules leading to cellular death, while antiapoptotic molecules including B-cell lymphoma 2 (BCL-2) prevent activation of prodeath proteins and counter-regulate apoptosis induction. Inhibition of these antiapoptotic regulators has become a promising strategy for anticancer treatment, but variable anticancer activities in different malignancies indicate the need for upfront identification of responsive patients. Here, we investigated the activity of the BCL-2 inhibitor venetoclax (VEN, ABT-199) in B-cell precursor acute lymphoblastic leukemia and found heterogeneous sensitivities in BCP-ALL cell lines and in a series of patient-derived primografts. To identify parameters of sensitivity and resistance, we evaluated genetic aberrations, gene-expression profiles, expression levels of apoptosis regulators, and functional apoptosis parameters analyzed by mitochondrial profiling using recombinant BH3-like peptides. Importantly, ex vivo VEN sensitivity was most accurately associated with functional BCL-2 dependence detected by BH3 profiling. Modeling clinical application of VEN in a preclinical trial in a set of individual ALL primografts, we identified that leukemia-free survival of VEN treated mice was precisely determined by functional BCL-2 dependence. Moreover, the predictive value of ex vivo measured functional BCL-2 dependence for preclinical in vivo VEN response was confirmed in an independent set of primograft ALL including T- and high risk-ALL. Thus, integrative analysis of the apoptosis signaling indicating mitochondrial addiction to BCL-2 accurately predicts antileukemia activity of VEN, robustly identifies VEN-responsive patients, and provides information for stratification and clinical guidance in future clinical applications of VEN in patients with ALL.[3] |
分子式 |
C45H50N7O7SCL
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分子量 |
868.4392
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精确质量 |
867.3181
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元素分析 |
C, 62.24; H, 5.80; Cl, 4.08; N, 11.29; O, 12.90; S, 3.69
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CAS号 |
1257044-40-8
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相关CAS号 |
Venetoclax-d8;1257051-06-1
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外观&性状 |
Yellow solid powder
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密度 |
1.3±0.1 g/cm3
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折射率 |
1.644
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LogP |
10.88
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tPSA |
186.58
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InChi Key |
LQBVNQSMGBZMKD-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C45H50ClN7O7S/c1-45(2)15-11-33(39(26-45)31-3-5-34(46)6-4-31)29-51-17-19-52(20-18-51)35-7-9-38(42(24-35)60-36-23-32-12-16-47-43(32)49-28-36)44(54)50-61(57,58)37-8-10-40(41(25-37)53(55)56)48-27-30-13-21-59-22-14-30/h3-10,12,16,23-25,28,30,48H,11,13-15,17-22,26-27,29H2,1-2H3,(H,47,49)(H,50,54)
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化学名 |
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide
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别名 |
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HS Tariff Code |
2934.99.9001
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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溶解度 (体外实验) |
DMSO: ~100 mg/mL (~115.1 mM)
Water: <1 mg/mL(slightly soluble or insoluble) Ethanol: <1 mg/mL |
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溶解度 (体内实验) |
配方 1 中的溶解度: 5 mg/mL (5.76 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (这些助溶剂从左到右依次添加,逐一添加), 悬浊液。
*生理盐水的制备:将 0.9 g 氯化钠溶解在 100 mL ddH₂O中,得到澄清溶液。 配方 2 中的溶解度: 2.5 mg/mL (2.88 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加,逐一添加), 悬浊液; 超声助溶。 例如,若需制备1 mL的工作液,可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中,混匀; 然后向上述溶液中加入50 μL Tween-80,混匀; 加入450 μL生理盐水定容至1 mL。 *生理盐水的制备:将 0.9 g 氯化钠溶解在 100 mL ddH₂O中,得到澄清溶液。 View More
配方 3 中的溶解度: 2.5 mg/mL (2.88 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加,逐一添加), 悬浊液; 通过加热和超声助溶。 配方 4 中的溶解度: 5% DMSO+50% PEG 300+5% Tween 80+ddH2O: 5 mg/mL 配方 5 中的溶解度: 20 mg/mL (23.03 mM) in 60% phosal 50 propylene glycol (PG), 30% polyethylene glycol 400 (PEG400), 10% ethanol (这些助溶剂从左到右依次添加,逐一添加), 悬浊液; 超声助溶。 1、请先配制澄清的储备液(如:用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液,按从左到右的顺序依次添加助溶剂,澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明,并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀/澄清;向上述体系中加入50 μL Tween-80,混合均匀/澄清;然后继续加入450 μL ddH2O (或 saline)定容至 1 mL; 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出,可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果,工作液请现配现用! 6、如不确定怎么将母液配置成体内动物实验的工作液,请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
制备储备液 | 1 mg | 5 mg | 10 mg | |
1 mM | 1.1515 mL | 5.7575 mL | 11.5149 mL | |
5 mM | 0.2303 mL | 1.1515 mL | 2.3030 mL | |
10 mM | 0.1151 mL | 0.5757 mL | 1.1515 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
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 ddH2O,混匀澄清。
(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT05464836 | Not yetrecrulting | Drug: CB-103/Drug:Venetoclax | LeukemiaLymphoblastic]Leukemta | M.D.Anderson Cancer Center | December 30 2022 | Phase 2 |
NCT05360160 | Recruiting | DrugSNDX-5613DrugVenetoclax]Drug-ASTX727 | LeukemiaLymphoblastic]Leukemta | M.D.Anderson Cancer Centerastex PharmaceuticalsIncSyndax Pharmaceutic als inc |
December 30 2022 | Phase 2 |