GSK1016790A |
Catalog No.GC17940
One-Click Copy Product Info
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GSK1016790A는 강력하고 선택적인 순시적 수용체 전위 벤질로이드 4 (TRPV4) 채널 활성제이다.
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Cas No.: 942206-85-1
Sample solution is provided at 25 µL, 10mM.
GSK1016790A는 강력하고 선택적인 순시적 수용체 전위 벤질로이드 4 (TRPV4) 채널 활성제이다. TRPV4는 Ca2+-투과성, 비선택적 양이온 채널로 온도 조절, 혈관 기능, 피부 장벽 기능, 기도와 폐 기능 그리고 통증 등 다양한 생리 기능에 참여한다[2]. GSK1016790A는 세포를 통과할 수 있는 파이페라지나미드 유도체로 4-α-PDD보다 약 300배 더 TRPV4 채널을 활성화시키는 효능이 있다[3].
체외 실험에서 GSK1016790A（10 nM）를 TRPV4-mCerulean과 TRPV4-mVenus를 전달한 HeLa 세포에 30분 동안 처리하여 TRPV4의 빠른 초기 활성화와 세포질 내 Ca2+ 수준의 현저하고 지속적인 증가를 유발했고 이는 약 3분 내에 빠르게 퓨즈드-스테디-스테이트로 붕괴되었다[4]. GSK1016790A（0.1-1000 nM）를 HEK 세포에 처리하여 Ca2+ 유입을 유도했고 인간과 쥐의 HEK 세포에 대한 EC50 값은 각각 18 nM과 2.1 nM였다[5].
체내 실험에서 GSK1016790A（10 mg/kg）를 구강 투여하여 죽상경화증 쥐를 3일 치료한 결과 죽상경화반의 발생과 대동맥동 내의 대식세포 함량을 현저하게 줄였다[6]. GSK1016790A（0.5 nM/5 mL）를 뇌실내 주사하여 뇌출혈（ICH） 쥐를 치료한 결과는 신경 및 운동기능 장애를 완화시키고 신경 활동의 표지인 c-fos의 표현 수준을 상향 조절했다[7].
References:
[1] Kittaka H, Yamanoi Y, Tominaga M. Transient receptor potential vanilloid 4 (TRPV4) channel as a target of crotamiton and its bimodal effects[J]. Pflügers Archiv-European Journal of Physiology, 2017, 469: 1313-1323.
[2] Nilius B, Voets T. The puzzle of TRPV4 channelopathies[J]. EMBO reports, 2013, 14(2): 152-163.
[3] Thorneloe K S, Sulpizio A C, Lin Z, et al. N-((1S)-1-{[4-((2S)-2-{[(2, 4-dichlorophenyl) sulfonyl] amino}-3-hydroxypropanoyl)-1-piperazinyl] carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I[J]. Journal of Pharmacology and Experimental Therapeutics, 2008, 326(2): 432-442.
[4] Jin M, Wu Z, Chen L, et al. Determinants of TRPV4 activity following selective activation by small molecule agonist GSK1016790A[J]. PloS one, 2011, 6(2): e16713.
[5] Fichna J, Poole D P, Veldhuis N, et al. Transient receptor potential vanilloid 4 inhibits mouse colonic motility by activating NO-dependent enteric neurotransmission[J]. Journal of Molecular Medicine, 2015, 93: 1297-1309.
[6] Xu S, Liu B, Yin M, et al. A novel TRPV4-specific agonist inhibits monocyte adhesion and atherosclerosis[J]. Oncotarget, 2016, 7(25): 37622.
[7] Asao Y, Tobori S, Kakae M, et al. Transient receptor potential vanilloid 4 agonist GSK1016790A improves neurological outcomes after intracerebral hemorrhage in mice[J]. Biochemical and Biophysical Research Communications, 2020, 529(3): 590-595.
| 세포 실험 [1]: | |
세포 라인 | HeLa세포 |
제조 방법 | HeLa 세포는 TRPV4-mCerulean과 TRPV4-mVenus로 공통 전달되어 GSK1016790A（10 nM）처리 후 0, 3, 10, 30분에 고정되었습니다. |
반응 조건 | 10nM; 0, 3, 10 및 30 min |
응용 분야 | GSK1016790A는 HeLa-TRPV4 세포에서 TRPV4 특이적인 Ca2+ 유입을 유발하지만 대조 점염된 세포에서는 유발하지 않습니다. |
| 동물 실험 [2]: | |
동물 모형 | ApoE−/− 쥐 |
제조 방법 | 쥐는 구강 투여하여 매일 한 번씩 3일 동안 운반제나 GSK1016790A（10 mg/kg 체중）를 투여했고 그 다음 날에는 복강 내（i.p.）주입으로 운반제（PBS）나 소쥐 재조합 텀네크신 분자 α（TNF-α）를 투여했습니다. 운반제나 TNF-α 처리 후 4시간에 쥐는 인트라비탈 현미경 검사를 준비했습니다. |
제형 | 10 mg/kg; p.o. |
응용 분야 | GSK1016790A로 치료된 쥐에서 대동맥 동맥 내 죽상경화반 및 대식세포 함량이 현저하게 줄어들었습니다. |
References: | |
| Cas No. | 942206-85-1 | SDF | |
| Chemical Name | N-[(1S)-1-[[4-[(2S)-2-[[(2,4-dichlorophenyl)sulfonyl]amino]-3-hydroxy-1-oxopropyl]-1-piperazinyl]carbonyl]-3-methylbutyl]-benzo[b]thiophene-2-carboxamide | ||
| Canonical SMILES | ClC1=CC=C(S(N[C@H](C(N2CCN(C([C@@H](NC(C3=CC4=C(C=CC=C4)S3)=O)CC(C)C)=O)CC2)=O)CO)(=O)=O)C(Cl)=C1 | ||
| Formula | C28H32Cl2N4O6S2 | M.Wt | 655.6 |
| Solubility | ≤10mg/ml in ethanol;15mg/ml in DMSO;15mg/ml in dimethyl formamide | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5253 mL | 7.6266 mL | 15.2532 mL |
| 5 mM | 305.1 μL | 1.5253 mL | 3.0506 mL |
| 10 mM | 152.5 μL | 762.7 μL | 1.5253 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 13 reference(s) in Google Scholar.)