RN1734

hTRPV4 (IC50 = 2.3 μM); mTRPV4 (IC50 = 5.9 μM); rTRPV4 (IC50 = 3.2 μM)[1]

CM（LPS 激活的星形胶质细胞群）细胞荧光引起的星形胶质细胞荧光率增加可被 RN-1734（27 小时；10 μM）逆转 [2]。 10μM； RN-1734 (27)。

RN-1734（0.5 μL；微注射泵；每天一次，持续 5 周）可显着逆转 CNP 美容并修复 CPZ 诱导的脱髓鞘小鼠的髓鞘形成 [2]。

TRPV4是香草醛受体TRPV1的近亲，由多种方式激活，如内源性脂质配体、低渗性、蛋白激酶，可能还有机械输入。虽然其在体内的多种作用正在用KO小鼠和选择性激动剂进行探索，但缺乏可用于检查TRPV4功能的选择性拮抗剂。在此，我们详细介绍了使用商业化合物的集中库来鉴定RN-1747和RN-1734，这两种结构相关的小分子分别具有TRPV4激动剂和拮抗剂的特性。通过电生理学和细胞内钙内流来表征它们对人类、大鼠和小鼠TRPV4的活性。值得注意的是，观察到拮抗剂RN-1734完全抑制了配体和低渗激活的TRPV4。此外，在TRP选择性面板（包括TRPV1、TRPV3和TRPM8）中发现RN-1734对TRPV4具有选择性，因此可能是TRPV4研究的有价值的药理学探针[3]。

细胞凋亡分析 [2]
细胞类型： 小胶质细胞
测试浓度： 27 小时
孵育持续时间： 10μM
实验结果： cleaved-caspase 3 阳性细胞的百分比显着减少。 ) 减弱了 CM 引起的 CNP 降低 [2]。

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蛋白质印迹分析[2]
细胞类型： 小胶质细胞
测试浓度： 27 hrs（小时）
孵育时间： 10 μM
实验结果： 缓解 CM（仅限 LPS）诱导的 CNP 降低。

Animal/Disease Models: CPZ-induced demyelination mouse model (C57BL/6 male mice) [2]
Doses: 0.5 μl (10 μM, dissolved in 5% DMSO and 0.9% NaCl)
Route of Administration: Microinjection pump 5-week
Experimental Results: Dramatically reversed the decrease in CNP protein and improved myelination in CPZ-induced demyelination mice.

[1]. Acidosis environment promotes osteoclast formation by acting on the last phase of preosteoclast differentiation: a study to elucidate the action points of acidosis and search for putative target molecules. Eur J Pharmacol. 2011 Aug 1;663(1-3):27-39.

[2]. TRPV4 Inhibition Improved Myelination and Reduced Glia Reactivity and Inflammation in a Cuprizone-Induced Mouse Model of Demyelination. Front Cell Neurosci. 2018 Nov 5;12:392.

[3]. Identification and characterization of novel TRPV4 modulators. Biochem Biophys Res Commun. 2009 Nov 20;389(3):490-4.

Acidosis promoted tartaric acid-resistant acid phosphatase-positive multinuclear cell (TRAP+MNC) or osteoclast formation. Large osteoclast or TRAP+LMNC formation was observed far more in an acidosis environment than in a physiologically neutral environment. One of the major action points of acidosis was determined to be located in the last phase of preosteoclast differentiation using a co-culture system and a soluble RANKL-dependent bone marrow cell culture system. On-going osteoclast formation in an acidosis environment markedly deteriorated when the medium was replaced with physiologically neutral medium within the first 6h; however, bone marrow cells previously stimulated in an acidosis environment for 9h differentiated into TRAP+LMNC in pH 7.4 medium. Messenger RNA (mRNA) expression levels of DC-STAMP, a key molecule in cell fusion, and NFATc1 did not increase in the acidosis environment compared with those under physiologically neutral conditions. Ruthenium red, a general TRP antagonist, deteriorated acidosis-promoted TRAP+LMNC formation. 4-Alpha-PDD, a TRPV4-specific agonist, added in the last 21 h of preosteoclast differentiation, potentiated TRAP+LMNC formation in a mild acidosis environment, showing synergism between TRPV4 activation and acidosis. RN1734, a TRPV4-specific antagonist, partly inhibited acidosis-promoted TRAP+LMNC formation. We thus narrowed down the major action points of acidosis in osteoclast formation and elucidated the characteristics of this system in detail. Our results show that acidosis effectively uses TRPV4 to drive large-scale cell fusion and also utilizes systems independently of TRPV4.[1]

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The inhibition of demyelination and the promotion of remyelination are both considerable challenges in the therapeutic process for many central nervous system (CNS) diseases. Increasing evidence has demonstrated that neuroglial activation and neuroinflammation are responsible for myelin sheath damage during demyelinating disorders. It has been revealed that the nonselective cation channel transient receptor potential vanilloid 4 (TRPV4) profoundly affects a variety of physiological processes, including inflammation. However, its roles and mechanisms in demyelination have remained unclear. Here, for the first time, we found that there was a significant increase in TRPV4 in the corpus callosum in a demyelinated mouse model induced by cuprizone (CPZ). RN-1734, a TRPV4-antagonist, clearly alleviated demyelination and inhibited glial activation and the production of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) without altering the number of olig2-positive cells. In vitro, RN-1734 treatment clearly inhibited the influx of calcium and decreased the levels of IL-1β and TNF-α in lipopolysaccharide (LPS)-activated microglial cells by suppressing NF-κB P65 phosphorylation. Apoptosis of oligodendrocyte induced by LPS-activated microglia was also alleviated by RN-1734. The results suggest that activation of TRPV4 in microglia is involved in oligodendrocyte apoptosis through the activation of the NF-κB signaling pathway, thus revealing a new mechanism of CNS demyelination.[2]

C14H22CL2N2O2S

353.3

352.078

946387-07-1

3601086

White to off-white solid powder

1.228g/cm3

445ºC at 760 mmHg

222.9ºC

1.536

4.862

57.79

1

4

7

21

410

0

O=S(N(C(C)C)CCNC(C)C)(C1C(Cl)=CC(Cl)=CC=1)=O

IHYZMEAZAIFMTN-UHFFFAOYSA-N

InChI=1S/C14H22Cl2N2O2S/c1-10(2)17-7-8-18(11(3)4)21(19,20)14-6-5-12(15)9-13(14)16/h5-6,9-11,17H,7-8H2,1-4H3

2,4-dichloro-N-(propan-2-yl)-N-{2-[(propan-2-yl)amino]ethyl}benzene-1-sulfonamide

RN-1734; RN 1734; 2,4-Dichloro-N-isopropyl-N-(2-isopropylaminoethyl)benzenesulfonamide; CHEMBL2324347; 2,4-dichloro-N-isopropyl-N-(2-(isopropylamino)ethyl)benzenesulfonamide; 2,4-dichloro-N-propan-2-yl-N-[2-(propan-2-ylamino)ethyl]benzenesulfonamide; RN1734.

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)

DMSO : ~25 mg/mL (~70.76 mM)

配方 1 中的溶解度: ≥ 3.25 mg/mL (9.20 mM) (饱和度未知) 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), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 32.5 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。

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配方 2 中的溶解度: ≥ 3.25 mg/mL (9.20 mM) (饱和度未知) 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), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 32.5 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。

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配方 3 中的溶解度: ≥ 3.25 mg/mL (9.20 mM) (饱和度未知) 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，若需制备1 mL的工作液，可将 100 μL 32.5 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

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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。