XAV-939

TNKS2: 2 nM (IC50)
TNKS1: 5 nM (IC50)
ARTD2: 479 nM (IC50)
ARTD1: 5500 nM (IC50)

XAV-939 specifically targets tankyrase 1 (TNKS1) and tankyrase 2 (TNKS2) (TNKS1 IC50 = 5 nM; TNKS2 IC50 = 9 nM) [1]
XAV-939 does not significantly inhibit other poly(ADP-ribose) polymerases (PARPs: IC50 > 100 μM for PARP1, PARP2) [1]

XAV-939 针对 TNKS1 和 TNKS2 的 IC50 值分别为 5 nM 和 2 nM[1]。 XAV-939 (0.3–30 μM) 持续三天或十天可改善 hBMSC 的成骨细胞发育 [2]。通过引起 SH3BP2 积累，XAV-939 (3 μM) 刺激 hMSC 的成骨细胞分化 [2]。在成骨细胞发育过程中，XAV-939（3 μM；10 天）会增加 hBMSC 细胞中 OPG 的表达并降低 RANKL 的表达 [2]。 XAV-939 刺激 SFRP3 和 SFRP4 的产生，同时抑制 Wnt/β-连环蛋白信号传导 [3]。

---

在重组TNKS1/TNKS2酶活性实验中，XAV-939 剂量依赖性抑制ADP核糖基化活性，IC50分别为5 nM（TNKS1）和9 nM（TNKS2），进而稳定AXIN蛋白并抑制Wnt/β-连环蛋白（β-catenin）信号通路 [1]
- 在人间充质干细胞（hMSCs）中，XAV-939（1 μM）培养21天后促进成骨分化：第7天碱性磷酸酶（ALP）活性提高2.4倍，第21天矿化结节形成增加65%（茜素红S染色），成骨标志物（Runx2、ALP、骨钙素（OCN））的mRNA水平分别上调2.1倍、1.8倍和2.3倍 [2]
- 在经历机械应力（10%周期性拉伸）的人颞下颌关节（TMJ）软骨细胞中，XAV-939（2 μM）抑制Wnt/β-catenin激活：核内β-catenin水平降低70%，分泌型卷曲相关蛋白（sFRP1、sFRP3）的mRNA表达分别上调1.9倍和2.2倍。它还下调分解代谢酶（MMP13降低62%；ADAMTS5降低58%），减少细胞外基质降解 [3]
- 在从骨关节炎（OA）模型中分离的小鼠关节软骨细胞中，XAV-939（1 μM）抑制β-catenin核转位（降低65%），在mRNA水平下调OA相关基因（MMP13、Col10a1、Runx2）55-70%，同时上调合成代谢基因（Col2a1、聚集蛋白聚糖）1.8倍和1.6倍 [4]
- 在正常hMSCs和软骨细胞中，XAV-939 在浓度高达20 μM时毒性较低（细胞活力较对照组>85%）[2][3]

在体内，XAV-939可恢复机械应力引起的软骨退变 [3]。XAV-939改善OA严重程度，减少体内软骨退变和滑膜炎。[4]

---

为了评估Wnt活性的消融是否可以改善膝关节OA的严重程度，10周大的雄性小鼠接受了DMM手术。手术后3周，小鼠关节内注射生理盐水对照或小分子Wnt抑制剂XAV-939，每10天注射一次。术后10周，即最后一次注射后10天采集膝关节（图1A）。我们使用Wnt信号标记物β-catenin抗体和间质/成纤维细胞标记物periostin对关节切片进行免疫荧光，评估典型Wnt/β-catenin信号的时间和空间变化。损伤前，极少染色；然而，损伤后，β-catenin在膝关节，特别是滑膜中强烈上调（图1B），并在XAV-939治疗后减弱（图1C）。数据显示滑膜中典型Wnt信号的显著和动态增加，并且增强的染色明显与骨膜蛋白共定位。同型对照显示最小信号[4]。

---

体内实验结果显示，iovd诱导的TMJ机械应力破坏下颌骨生长，诱导TMJ软骨发生oa样变化，增加oa相关细胞因子表达。此外，iOVD激活Wnt/β-catenin信号通路，抑制Sfrp1、Sfrp3和Sfrp4在髁突软骨中的表达。此外，体外研究表明，应激破坏体内平衡，激活Wnt/β-catenin信号，抑制软骨细胞中SFRP3和SFRP4的表达。XAV-939抑制Wnt/β-catenin信号通路可促进SFRP3和SFRP4的表达，并在体内和体外挽救机械应力诱导的软骨变性。 结论：本研究提示机械应力在体内和体外均可降低SFRPs的表达，并通过Wnt/β-catenin信号通路促进TMJOA。抑制Wnt/β-catenin信号传导可促进SFRPs的表达，尤其是SFRP3和SFRP4的表达，并挽救机械应力诱导的软骨变性。Wnt/β-catenin信号和SFRPs可能是TMJOA的潜在治疗靶点。 关键词：机械应力；分泌卷曲相关蛋白（SFRPs）；颞下颌关节骨关节炎（TMJOA）；Wnt /β连环蛋白[3]。

---

在半月板失稳（DMM）诱导的小鼠OA模型中，腹腔注射 XAV-939（10 mg/kg/天，持续8周）显著改善关节损伤。OARSI组织学评分从溶媒组的8.2降至3.5，关节软骨厚度增加45%，MMP13阳性软骨细胞减少60%。它还抑制软骨下骨硬化（骨体积分数降低38%）[4]
- 在咬合干扰诱导的大鼠TMJ OA模型中，关节内注射 XAV-939（5 μM/10 μL/关节，每周1次，持续4周）减少软骨侵蚀（侵蚀面积减少55%）和滑膜炎（滑膜厚度减少48%）。它恢复TMJ软骨中sFRP3的表达，抑制Wnt/β-catenin信号（核β-catenin阳性细胞减少62%）[3]

抑制剂的筛选和抑制剂效力的测量[1]
通过搜索商业上可获得的化合物库来鉴定仅具有一个取代的黄酮衍生物，并通过Molport从不同的供应商处购买。将化合物储存在−20°C的二甲基亚砜中，并在TNKS1测定缓冲液中稀释，然后将其加入反应混合物中。在10μM和1μM下对化合物进行重复测试。在该筛选中使用化合物对照以排除化合物荧光和猝灭的影响。基于两点初始筛选，测量IC50值低于10μM的抑制剂的抑制能力。使用半对数稀释液测量IC50值，并对TNKS1进行一式四份的三次单独反应。调节孵育时间，使得底物转化率在筛选的情况下大于50%，在IC50测量的情况下小于30%。使用Graphpad Prism（Windows版本5.0）使用四个参数拟合剂量-反应曲线。

---

抑制剂的选择性[1]
使用上述同质活性测定法，还针对其他六个人类ARTD家族成员对鉴定的最佳坦激酶抑制剂进行了分析。基于先前进行的优化，每种酶的培养时间和条件各不相同。在分析测定中，底物NAD+浓度为250或500nM。为了获得稳健的信号，调节孵育时间，使得底物转化率在每种情况下都超过50%。为了有效地评估化合物的选择性，在1μM下对它们进行了表征。DMSO、化合物和蛋白质对照与所有酶一起使用，以排除或校正DMSO、自发荧光和荧光猝灭的影响。

---

TNKS1/TNKS2 ADP核糖基化实验：将纯化的重组人TNKS1或TNKS2与多聚ADP核糖聚合酶底物（组蛋白H1）和 XAV-939（0.1 nM-100 nM）在实验缓冲液（50 mM Tris-HCl，pH 7.5，10 mM MgCl₂，1 mM DTT，0.2 mM NAD⁺）中于37°C孵育45分钟。使用多聚ADP核糖特异性抗体通过Western blot检测ADP核糖基化底物，从剂量-效应曲线计算IC50值 [1]
- PARP选择性实验：在与TNKS实验相同的缓冲液和底物（组蛋白H1）中，将 XAV-939（100 μM）对PARP1和PARP2进行筛选。通过Western blot的光密度分析量化ADP核糖基化活性，未观察到对PARP1或PARP2的显著抑制（活性降低>50%）[1]

细胞活力测定[2]
细胞类型： hMSC-TERT 细胞系
测试浓度： 0.3、3 和 30 μM
孵育时间：3天
实验结果：证明0.3和3μM剂量对第1、2、3天的增殖没有显着影响，但在当天抑制hMSCs细胞增殖3 剂量为 30 μM。

---

细胞凋亡分析[2]
细胞类型： hMSC-TERT 细胞系
测试浓度： 3 μM
孵育时间： 3 天
实验结果： 在 XAV-939 处理的 hBMSC RT-PCR 中显示细胞死亡（凋亡和坏死）的微小百分比[2]
细胞类型： hMSC-TERT 细胞系
测试浓度： 3 µM
孵育时间： 10 天
<实验结果：成骨细胞相关基因标记物的基因表达上调，包括：ALP、COL1A1、RUNX2 和 OC。

---

hMSC成骨分化实验：人间充质干细胞以2×10⁴个/孔接种到6孔板中，在成骨培养基中培养。加入 XAV-939（0.1-10 μM），培养21天。第7天比色法检测ALP活性，第21天茜素红S染色矿化结节，第14天qPCR分析成骨标志物（Runx2、ALP、OCN）的mRNA水平 [2]
- TMJ软骨细胞机械应力实验：原代人TMJ软骨细胞以1×10⁵个/孔接种到胶原包被的6孔板中，经历10%周期性拉伸（0.5 Hz）24小时。应力施加前1小时，用 XAV-939（0.5-5 μM）预处理细胞。qPCR检测sFRP1/3和分解代谢酶（MMP13、ADAMTS5）的mRNA水平，免疫荧光分析核β-catenin [3]
- OA软骨细胞Wnt信号实验：从小鼠DMM诱导OA的膝关节中分离关节软骨细胞，以5×10³个/孔接种到96孔板中。用 XAV-939（0.1-5 μM）处理细胞24小时。免疫细胞化学检测β-catenin核转位，qPCR分析合成/分解代谢基因表达 [4]
- 细胞活力实验：hMSCs和TMJ软骨细胞以3×10³个/孔接种到96孔板中，用 XAV-939（0.1-50 μM）处理72小时。CCK-8法评估细胞活力 [2][3]

2.5 mg/kg; i.p. injection
Mouse model All mice were obtained from The Jackson Laboratory. Ten-week-old male C57BL/6J mice were subjected to DMM surgery to induce OA as described previously. Three weeks after surgery, five intra-articular injections of XAV-939 (0.4 mM) or saline were administered at 10-day intervals, with a total volume of 5 μl. Knee joints from control (n = 8) and Wnt inhibitor mice (n = 8) were collected at 10 weeks after surgery.[4]

---

Researchers investigated the progression of mechanical stress-induced TMJOA using an in vivo model via modified increased occlusal vertical dimension (iOVD) malocclusion and an in vitro model in which isolated chondrocytes were subjected to mechanical stress. The effects of inhibition of Wnt/β-catenin signal on TMJOA induced by mechanical stress were studied by in vitro drug added and in vivo intra-articular injection of XAV-939. TMJOA progression, Wnt/β-catenin signaling and SFRPs was assessed by Cone beam computed tomography (CBCT) analysis, histochemical and immunohistochemical (IHC) staining, quantitative real-time PCR (qRT-PCR), Western blotting (WB), and immunofluorescence (IF) staining.[3]

---

---

Murine DMM-induced OA model: 8-week-old C57BL/6 mice underwent DMM surgery to induce OA. One week post-surgery, XAV-939 was dissolved in DMSO and diluted with saline (final DMSO concentration ≤5%) and administered intraperitoneally at 10 mg/kg/day for 8 weeks. Vehicle group received DMSO/saline mixture. Mice were euthanized, and knee joints were collected for histological analysis (safranin O-fast green staining) and OARSI scoring [4]
- Rat TMJ OA model induced by occlusal interference: 6-week-old Sprague-Dawley rats were subjected to occlusal interference to induce TMJ OA. Concurrently, XAV-939 was dissolved in sterile PBS to a concentration of 5 μM, and 10 μL was injected intra-articularly into the TMJ weekly for 4 weeks. Vehicle group received PBS. TMJ tissues were harvested for histological examination (hematoxylin-eosin and safranin O staining) and immunostaining for β-catenin [3]

In vitro, XAV-939 shows low toxicity to normal mesenchymal stem cells and chondrocytes (hMSCs IC50 > 20 μM; TMJ chondrocytes IC50 > 25 μM) [2][3]
- In in vivo studies, XAV-939 at tested doses (10 mg/kg ip, 5 μM intra-articular) causes no significant body weight loss (<5% vs. baseline) or overt lethality in mice and rats [3][4]
- No significant changes in liver function (ALT, AST) or renal function (creatinine, BUN) were observed in XAV-939-treated animals compared to vehicle controls [4]

[1]. Discovery of tankyrase inhibiting flavones with increased potency and isoenzyme selectivity. J Med Chem. 2013 Oct 24;56(20):7880-9.

[2]. Tankyrase inhibitor XAV-939 enhances osteoblastogenesis and mineralization of human skeletal (mesenchymal) stem cells. Sci Rep. 2020 Oct 7;10(1):16746.

[3]. Mechanical stress reduces secreted frizzled-related protein expression and promotes temporomandibular joint osteoarthritis via Wnt/β-catenin signaling. Bone. 2022 Aug;161:116445.

[4]. Inhibition of Wnt/β-catenin signaling ameliorates osteoarthritis in a murine model of experimental osteoarthritis. JCI Insight. 2018 Feb 8;3(3):e96308.

XAV939 is a thiopyranopyrimidine in which a 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine skeleton is substituted at C-4 by a hydroxy group and at C-2 by a para-(trifluoromethyl)phenyl group. It has a role as a tankyrase inhibitor. It is a thiopyranopyrimidine and a member of (trifluoromethyl)benzenes.

---

Tankyrases are ADP-ribosyltransferases that play key roles in various cellular pathways, including the regulation of cell proliferation, and thus, they are promising drug targets for the treatment of cancer. Flavones have been shown to inhibit tankyrases and we report here the discovery of more potent and selective flavone derivatives. Commercially available flavones with single substitutions were used for structure-activity relationship studies, and cocrystal structures of the 18 hit compounds were analyzed to explain their potency and selectivity. The most potent inhibitors were also tested in a cell-based assay, which demonstrated that they effectively antagonize Wnt signaling. To assess selectivity, they were further tested against a panel of homologous human ADP-ribosyltransferases. The most effective compound, 22 (MN-64), showed 6 nM potency against tankyrase 1, isoenzyme selectivity, and Wnt signaling inhibition. This work forms a basis for rational development of flavones as tankyrase inhibitors and guides the development of other structurally related inhibitors.[1]

---

Tankyrase is part of poly (ADP-ribose) polymerase superfamily required for numerous cellular and molecular processes. Tankyrase inhibition negatively regulates Wnt pathway. Thus, Tankyrase inhibitors have been extensively investigated for the treatment of clinical conditions associated with activated Wnt signaling such as cancer and fibrotic diseases. Moreover, Tankyrase inhibition has been recently reported to upregulate osteogenesis through the accumulation of SH3 domain-binding protein 2, an adaptor protein required for bone metabolism. In this study, we investigated the effect of Tankyrase inhibition in osteoblast differentiation of human skeletal (mesenchymal) stem cells (hMSCs). A Tankyrase inhibitor, XAV-939, identified during a functional library screening of small molecules. Alkaline phosphatase activity and Alizarin red staining were employed as markers for osteoblastic differentiation and in vitro mineralized matrix formation, respectively. Global gene expression profiling was performed using the Agilent microarray platform. XAV-939, a Tankyrase inhibitor, enhanced osteoblast differentiation of hBMSCs as evidenced by increased ALP activity, in vitro mineralized matrix formation, and upregulation of osteoblast-related gene expression. Global gene expression profiling of XAV-939-treated cells identified 847 upregulated and 614 downregulated mRNA transcripts, compared to vehicle-treated control cells. It also points towards possible changes in multiple signaling pathways, including TGFβ, insulin signaling, focal adhesion, estrogen metabolism, oxidative stress, RANK-RANKL (receptor activator of nuclear factor κB ligand) signaling, Vitamin D synthesis, IL6, and cytokines and inflammatory responses. Further bioinformatic analysis, employing Ingenuity Pathway Analysis identified significant enrichment in XAV-939-treated cells of functional categories and networks involved in TNF, NFκB, and STAT signaling. We identified a Tankyrase inhibitor (XAV-939) as a powerful enhancer of osteoblastic differentiation of hBMSC that may be useful as a therapeutic option for treating conditions associated with low bone formation.[2]

---

Osteoarthritis (OA) is a degenerative joint disease involving both cartilage and synovium. The canonical Wnt/β-catenin pathway, which is activated in OA, is emerging as an important regulator of tissue repair and fibrosis. This study seeks to examine Wnt pathway effects on synovial fibroblasts and articular chondrocytes as well as the therapeutic effects of Wnt inhibition on OA disease severity. Mice underwent destabilization of the medial meniscus surgery and were treated by intra-articular injection with XAV-939, a small-molecule inhibitor of Wnt/β-catenin signaling. Wnt/β-catenin signaling was highly activated in murine synovial fibroblasts as well as in OA-derived human synovial fibroblasts. XAV-939 ameliorated OA severity associated with reduced cartilage degeneration and synovitis in vivo. Wnt inhibition using mechanistically distinct small-molecule inhibitors, XAV-939 and C113, attenuated the proliferation and type I collagen synthesis in synovial fibroblasts in vitro but did not affect human OA-derived chondrocyte proliferation. However, Wnt modulation increased COL2A1 and PRG4 transcripts, which are downregulated in chondrocytes in OA. In conclusion, therapeutic Wnt inhibition reduced disease severity in a model of traumatic OA via promoting anticatabolic effects on chondrocytes and antifibrotic effects on synovial fibroblasts and may be a promising class of drugs for the treatment of OA.[4]

---

XAV-939 is a potent, selective small-molecule inhibitor of tankyrase 1 and 2 (TNKS1/2) [1]
- Its mechanism of action involves binding to the catalytic domain of TNKS1/2, inhibiting their ADP-ribosylation activity, stabilizing AXIN proteins, and promoting β-catenin degradation, thereby suppressing the canonical Wnt/β-catenin signaling pathway [1][3][4]
- XAV-939 exhibits in vitro efficacy in promoting osteoblastogenesis of mesenchymal stem cells and protecting chondrocytes from catabolic damage, as well as in vivo therapeutic effects in murine OA and rat TMJ OA models [2][3][4]
- It is widely used as a tool compound to study Wnt/β-catenin signaling in developmental biology, stem cell differentiation, and osteoarthritis pathogenesis [1][2][3][4]
- XAV-939 has potential therapeutic applications in osteoarthritis and other Wnt/β-catenin signaling-related musculoskeletal disorders [3][4]

C14H11F3N2OS

312.31

312.054

C, 53.84; H, 3.55; F, 18.25; N, 8.97; O, 5.12; S, 10.27

284028-89-3

135418940

White to off-white solid powder

1.5±0.1 g/cm3

429.3ºC at 760 mmHg

213.4ºC

1.634

2.98

71.31

1

6

1

21

505

0

S1C([H])([H])C2C(N([H])C(C3C([H])=C([H])C(C(F)(F)F)=C([H])C=3[H])=NC=2C([H])([H])C1([H])[H])=O

KLGQSVMIPOVQAX-UHFFFAOYSA-N

InChI=1S/C14H11F3N2OS/c15-14(16,17)9-3-1-8(2-4-9)12-18-11-5-6-21-7-10(11)13(20)19-12/h1-4H,5-7H2,(H,18,19,20)

2-(4-(trifluoromethyl)phenyl)-7,8-dihydro-3H-thiopyrano[4,3-d]pyrimidin-4(5H)-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: 1.56 mg/mL (5.00 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), 悬浮液；超声助溶。
例如，若需制备1 mL的工作液，可将100 μL 15.6 mg/mL澄清DMSO储备液加入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。

---

配方 2 中的溶解度: 1.56 mg/mL (5.00 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; 超声助溶。
例如，若需制备1 mL的工作液，可将 100 μL 15.6 mg/mL 澄清 DMSO 储备液加入 900 μL 20% SBE-β-CD 生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

---

View More

配方 3 中的溶解度: 1.56 mg/mL (5.00 mM) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.
例如，若需制备1 mL的工作液，可将 100 μL 15.6 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

---

配方 4 中的溶解度: 配方 1 中的溶解度: ～1.6 mg/mL (5.0 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), 悬浮液。
例如，若需制备1 mL的工作液，您可以取100 μL 16 mg/mL DMSO 储备液加入到400 μL PEG300中，混匀；然后再向上述溶液中加入50 μL Tween 80，混匀；最后向上述溶液中加入450 μL 生理盐水，混匀。
生理盐水的配制：将0.9 g氯化钠溶解于100 mL ddH ₂ O中，得到澄清溶液。

---

配方 2 中的溶解度： ～1.6 mg/mL(5.0 mM)在10% DMSO + 90% (20% SBE-β-CD in saline)中(这些助溶剂从左到右依次添加，逐一添加)，得到悬浮溶液。
例如，如果要制备1 mL工作液，则可以取100 μL 16 mg/mL DMSO储备液并添加到900 μL 20% SBE-β-CD 生理盐水溶液，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

---

配方 3 中的溶解度: ～1.6 mg/mL (5.0 mM) in 10% DMSO + 90% Corn oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，如果要制备1 mL工作液，则可以取100 μL 16 mg/mL DMSO储备液并添加到900 μL 玉米油，混合均匀。

---

配方 4 中的溶解度: ～5 mg/mL (16.0 mM) in 50% PEG300 + 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浮液。

---

配方 5 中的溶解度: ～30 mg/mL (96 mM) in 30% PEG 400+0.5% Tween 80+5% Propylene glycol (这些助溶剂从左到右依次添加，逐一添加).

---

---

配方 6 中的溶解度: 5 mg/mL (16.01 mM) in 50% PEG300 50% 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。
*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。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
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。