SKF-96365 HCl | CAS# 130495-35-1 | TRPC channel blocker

MedKoo Cat#: 526683 | Name: SKF-96365 HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

SKF-96365 is a selective TRPC channel blocker. SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIγ/AKT-mediated pathway. SKF-96365 strongly inhibits voltage-gated sodium current in rat ventricular myocytes. SKF 96365 inhibits glioblastoma cell growth by enhancing reverse mode of the Na(+) /Ca(2+) exchanger and increasing intracellular Ca(2+). SKF-96365 attenuates toxin-induced neuronal injury through opposite regulatory effects on Homer1a and Homer1b/c in cultured rat mesencephalic cells.

Chemical Structure

SKF-96365 HCl

CAS#130495-35-1 (HCl)

Theoretical Analysis

MedKoo Cat#: 526683

Name: SKF-96365 HCl

CAS#: 130495-35-1 (HCl)

Chemical Formula: C22H27ClN2O3

Exact Mass: 0.0000

Molecular Weight: 402.92

Elemental Analysis: C, 65.58; H, 6.75; Cl, 8.80; N, 6.95; O, 11.91

Price and Availability

Size	Price	Availability
50mg	USD 750.00	2 Weeks
100mg	USD 1,250.00	2 Weeks
200mg	USD 1,950.00	2 Weeks
500mg	USD 2,950.00	2 Weeks
1g	USD 3,850.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Related CAS #

130495-35-1 (HCl) 162849-90-3 (free base)

Synonym

SKF-96365; SKF 96365; SKF96365; SKF-96,365; SKF 96,365; SKF96,365.

IUPAC/Chemical Name

1-(2-(4-methoxyphenyl)-2-(3-(4-methoxyphenyl)propoxy)ethyl)-1H-imidazole hydrochloride

InChi Key

FWLPKVQUECFKSW-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H26N2O3.ClH/c1-25-20-9-5-18(6-10-20)4-3-15-27-22(16-24-14-13-23-17-24)19-7-11-21(26-2)12-8-19;/h5-14,17,22H,3-4,15-16H2,1-2H3;1H

SMILES Code

COC1=CC=C(CCCOC(C2=CC=C(OC)C=C2)CN3C=CN=C3)C=C1.[H]Cl

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

SKF-96365 inhibits the receptor-mediated influx of calcium via voltage-gated calcium channels with an IC50 value of approximately 10 µM. It inhibits the acetylcholine-induced depolarization of circular smooth muscle in a dose-dependent manner at 3-50 µM.

In vitro activity:

The study highlights SKF‑96365 as a potential therapeutic option to inhibit cardiac hypertrophy by targeting the TRPC pathway. H9c2 cells treated with Ang II showed increased hypertrophy markers and TRPC-related proteins. SKF‑96365 treatment reversed these effects, suggesting that the TRPC pathway is involved in Ang II-induced hypertrophy. Reference: Mol Med Rep. 2020 Feb;21(2):806-814. https://pubmed.ncbi.nlm.nih.gov/31974621/

In vivo activity:

SKF-96365 can effectively improve myocardial fibrosis in type-II diabetic rats. The weight of diabetic rats decreased and whole heart weight and left ventricular weight increased. However, the diabetic rats treated with SKF-96365 had less severe diabetic cardiomyopathy than diabetic rats that did not receive treatment. Reference: Front Biosci (Landmark Ed). 2023 Sep 27;28(9):231. https://pubmed.ncbi.nlm.nih.gov/37796683/

	Solvent	mg/mL	mM	comments
Solubility
	Water	8.1	20.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 402.92 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Cheng H, Li J, Wu Q, Zheng X, Gao Y, Yang Q, Sun N, He M, Zhou Y. Effect of SKF‑96365 on cardiomyocyte hypertrophy induced by angiotensin II. Mol Med Rep. 2020 Feb;21(2):806-814. doi: 10.3892/mmr.2019.10877. Epub 2019 Dec 11. PMID: 31974621; PMCID: PMC6947876. 2. Chen T, Zhu J, Zhang C, Huo K, Fei Z, Jiang XF. Protective effects of SKF-96365, a non-specific inhibitor of SOCE, against MPP+-induced cytotoxicity in PC12 cells: potential role of Homer1. PLoS One. 2013;8(1):e55601. doi: 10.1371/journal.pone.0055601. Epub 2013 Jan 31. PMID: 23383239; PMCID: PMC3561331. 3. Liu HZ, Wu W. Effect of SKF96365 on Myocardial Fibrosis in Type-II Diabetic Rats. Front Biosci (Landmark Ed). 2023 Sep 27;28(9):231. doi: 10.31083/j.fbl2809231. PMID: 37796683. 4. Šutovská M, Kocmálová M, Kazimierová I, Forsberg CIN, Jošková M, Adamkov M, Fraňová S. Effects of Inhalation of STIM-Orai Antagonist SKF 96365 on Ovalbumin-Induced Airway Remodeling in Guinea Pigs. Adv Exp Med Biol. 2021;1335:87-101. doi: 10.1007/5584_2021_633. PMID: 33742420.

In vitro protocol:

In vivo protocol:

1. Liu HZ, Wu W. Effect of SKF96365 on Myocardial Fibrosis in Type-II Diabetic Rats. Front Biosci (Landmark Ed). 2023 Sep 27;28(9):231. doi: 10.31083/j.fbl2809231. PMID: 37796683. 2. Šutovská M, Kocmálová M, Kazimierová I, Forsberg CIN, Jošková M, Adamkov M, Fraňová S. Effects of Inhalation of STIM-Orai Antagonist SKF 96365 on Ovalbumin-Induced Airway Remodeling in Guinea Pigs. Adv Exp Med Biol. 2021;1335:87-101. doi: 10.1007/5584_2021_633. PMID: 33742420.

1: Dubourg A, Harnois T, Cousin L, Constantin B, Bourmeyster N. SKF-96365 Expels Tyrosine Kinase Inhibitor-Treated CML Stem and Progenitor Cells from the HS27A Stromal Cell Niche in a RhoA-Dependent Mechanism. Cancers (Basel). 2024 Aug 8;16(16):2791. doi: 10.3390/cancers16162791. PMID: 39199564; PMCID: PMC11352811. 2: Xu K, Shimizu M, Yamashita T, Fujiwara M, Oikawa S, Ou G, Takazakura N, Kusakabe T, Takahashi K, Kato K, Yoshioka K, Obara K, Tanaka Y. Inhibitory mechanisms of docosahexaenoic acid on carbachol-, angiotensin II-, and bradykinin-induced contractions in guinea pig gastric fundus smooth muscle. Sci Rep. 2024 May 22;14(1):11720. doi: 10.1038/s41598-024-62578-y. PMID: 38778154; PMCID: PMC11111694. 3: Kohashi H, Nagata R, Tamenori Y, Amatani T, Ueda Y, Mori Y, Kasahara Y, Obika S, Shimojo M. A novel transient receptor potential C3/C6 selective activator induces the cellular uptake of antisense oligonucleotides. Nucleic Acids Res. 2024 May 22;52(9):4784-4798. doi: 10.1093/nar/gkae245. PMID: 38621757; PMCID: PMC11109983. 4: Obara K, Ichimura A, Arai T, Fujiwara M, Otake M, Yamada N, Yoshioka K, Kusakabe T, Takahashi K, Kato K, Tanaka Y. Platelet-activating factor contracts guinea pig esophageal muscularis mucosae by stimulating extracellular Ca2+ influx through diltiazem-insensitive Ca2+ channels. J Pharmacol Sci. 2024 Apr;154(4):256-263. doi: 10.1016/j.jphs.2024.01.009. Epub 2024 Feb 5. PMID: 38485343. 5: Allam S, Krüger D, Michel K, Schnabl K, Klingenspor M, Schemann M, Annaházi A. Mechanisms involved in the muscle relaxing effects of STW 5 in guinea pig stomach. Neurogastroenterol Motil. 2024 Oct;36(10):e14761. doi: 10.1111/nmo.14761. Epub 2024 Feb 11. PMID: 38342975. 6: Liu HZ, Wu W. Effect of SKF96365 on Myocardial Fibrosis in Type-II Diabetic Rats. Front Biosci (Landmark Ed). 2023 Sep 27;28(9):231. doi: 10.31083/j.fbl2809231. PMID: 37796683. 7: Liu G, Obara K, Yoshioka K, Tanaka Y. Pharmacological Studies on the Ca2+ Influx Pathways in Platelet-Activating Factor (PAF)-Induced Mouse Urinary Bladder Smooth Muscle Contraction. Biol Pharm Bull. 2023;46(7):997-1003. doi: 10.1248/bpb.b22-00923. PMID: 37394649. 8: Ben Dhaou C, Terrié E, Déliot N, Harnois T, Cousin L, Arnault P, Constantin B, Moyse E, Coronas V. Neural stem cell self-renewal stimulation by store- operated calcium entries in adult mouse area postrema: influence of leptin. Front Cell Neurosci. 2023 Jun 9;17:1200360. doi: 10.3389/fncel.2023.1200360. PMID: 37361995; PMCID: PMC10287973. 9: Obara K, Kaneko M, Yamashita M, Liu G, Yoshioka K, Tanaka Y. Platelet- activating factor (PAF) enhances guinea pig detrusor smooth muscle contractile activities by stimulating voltage-dependent Ca2+ channels and store- operated Ca2+ channels. J Pharmacol Sci. 2023 Jun;152(2):123-127. doi: 10.1016/j.jphs.2023.04.004. Epub 2023 Apr 13. PMID: 37169476. 10: Torrezan-Nitao E, Brown SG, Lefievre L, Morris J, Correia J, Harper CV, Publicover S. SKF96365 modulates activity of CatSper channels in human sperm. Mol Hum Reprod. 2023 May 31;29(6):gaad015. doi: 10.1093/molehr/gaad015. PMID: 37104740; PMCID: PMC10266451. 11: Pasupuleti SK, Ramdas B, Burns SS, Palam LR, Kanumuri R, Kumar R, Pandhiri TR, Dave UP, Yellapu NK, Zhou X, Zhang C, Sandusky GE, Yu Z, Honigberg MC, Bick AG, Griffin GK, Niroula A, Ebert BL, Paczesny S, Natarajan P, Kapur R. Obesity- induced inflammation exacerbates clonal hematopoiesis. J Clin Invest. 2023 Jun 1;133(11):e163968. doi: 10.1172/JCI163968. PMID: 37071471; PMCID: PMC10231999. 12: Obara K, Yoshioka K, De Dios Regadera M, Matsuyama Y, Yashiro A, Miyokawa M, Iura R, Tanaka Y. Phenylephrine-Induced Contraction in Guinea Pig Thoracic Aorta Is Triggered by Stimulation of α1L-Adrenoceptors Functionally Coupled with Store-Operated Ca2+ Channels and Voltage-Dependent Ca2+ Channels. Biol Pharm Bull. 2023;46(2):309-319. doi: 10.1248/bpb.b22-00754. PMID: 36724959. 13: Williams PDE, Kashyap SS, McHugh MA, Brewer MT, Robertson AP, Martin RJ. Diethylcarbamazine, TRP channels and Ca2+ signaling in cells of the Ascaris intestine. Sci Rep. 2022 Dec 9;12(1):21317. doi: 10.1038/s41598-022-25648-7. PMID: 36494409; PMCID: PMC9734116. 14: Ding S, Yang L, Huang L, Kong L, Chen M, Su Y, Li X, Dong X, Han Y, Li W, Li W. Chronic glucocorticoid exposure accelerates Aβ generation and neurotoxicity by activating calcium-mediated CN-NFAT1 signaling in hippocampal neurons in APP/PS1 mice. Food Chem Toxicol. 2022 Oct;168:113407. doi: 10.1016/j.fct.2022.113407. Epub 2022 Sep 6. PMID: 36075474. 15: Xu K, Shimizu M, Murai C, Fujisawa M, Ito D, Saitoh N, Nakagome Y, Yamashita M, Murata A, Oikawa S, Ou G, Yoshioka K, Obara K, Tanaka Y. Docosahexaenoic acid and eicosapentaenoic acid strongly inhibit prostanoid TP receptor-dependent contractions of guinea pig gastric fundus smooth muscle. Pharmacol Res Perspect. 2022 Jun;10(3):e00952. doi: 10.1002/prp2.952. PMID: 35466586; PMCID: PMC9035583. 16: Yang L, Pierce S, Gould TW, Craviso GL, Leblanc N. Ultrashort nanosecond electric pulses activate a conductance in bovine adrenal chromaffin cells that involves cation entry through TRPC and NALCN channels. Arch Biochem Biophys. 2022 Jul 15;723:109252. doi: 10.1016/j.abb.2022.109252. Epub 2022 Apr 15. PMID: 35436445. 17: Bai LP, Chen YL, Zheng A. Pharmacological targeting transient receptor potential canonical channel 6 modulates biological behaviors for cervical cancer HeLa and SiHA cell. Cancer Cell Int. 2022 Apr 7;22(1):145. doi: 10.1186/s12935-022-02556-4. PMID: 35392906; PMCID: PMC8991836. 18: Miyaki R, Yamamura A, Kawade A, Fujiwara M, Kondo R, Suzuki Y, Yamamura H. SKF96365 activates calcium-sensing receptors in pulmonary arterial smooth muscle cells. Biochem Biophys Res Commun. 2022 Jun 4;607:44-48. doi: 10.1016/j.bbrc.2022.03.121. Epub 2022 Mar 25. PMID: 35366542. 19: Tedeschi V, Sisalli MJ, Pannaccione A, Piccialli I, Molinaro P, Annunziato L, Secondo A. Na+/Ca2+ exchanger isoform 1 (NCX1) and canonical transient receptor potential channel 6 (TRPC6) are recruited by STIM1 to mediate Store-Operated Calcium Entry in primary cortical neurons. Cell Calcium. 2022 Jan;101:102525. doi: 10.1016/j.ceca.2021.102525. Epub 2021 Dec 30. PMID: 34995919. 20: Ou G, Fujisawa M, Yashiro A, Xu K, Yoshioka K, Obara K, Tanaka Y. Prostanoid TP receptor stimulation enhances contractile activities in guinea pig urinary bladder smooth muscle through activation of Ca2+ entry channels: Potential targets in the treatment of urinary bladder contractile dysfunction. Life Sci. 2021 Dec 15;287:120130. doi: 10.1016/j.lfs.2021.120130. Epub 2021 Nov 10. PMID: 34767807.