HC-067047
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MedKoo CAT#: 530432

CAS#: 883031-03-6

Description: HC-067047 is a potent and selective TRPV4 antagonist. HC-067047 increases functional bladder capacity and reduces micturition frequency in WT mice and rats with cystitis. HC-067047 did not affect bladder function in Trpv4(-/-) mice, demonstrating that its in vivo effects are on target. HC-067047 may provide a promising means of treating bladder

Chemical Structure

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HC-067047
CAS# 883031-03-6
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 530432
Name: HC-067047
CAS#: 883031-03-6
Chemical Formula: C26H28F3N3O2
Exact Mass: 471.21
Molecular Weight: 471.524
Elemental Analysis: C, 66.23; H, 5.99; F, 12.09; N, 8.91; O, 6.79

Price and Availability

Size Price Availability Quantity
5mg USD 250
25mg USD 650
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Synonym: HC-067047; HC 067047; HC067047.

IUPAC/Chemical Name: 2-Methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide

InChi Key: NCZYSQOTAYFTNM-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H28F3N3O2/c1-19-23(25(33)30-22-10-5-9-21(17-22)26(27,28)29)18-24(20-7-3-2-4-8-20)32(19)12-6-11-31-13-15-34-16-14-31/h2-5,7-10,17-18H,6,11-16H2,1H3,(H,30,33)

SMILES Code: O=C(C1=C(C)N(CCCN2CCOCC2)C(C3=CC=CC=C3)=C1)NC4=CC=CC(C(F)(F)F)=C4

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 DMSO

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:
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Biological target: HC-067047 is a potent and selective TRPV4 antagonist and reversibly inhibits currents through the human, rat, and mouse TRPV4 orthologs with IC50 values of 48 nM, 133 nM, and 17 nM, respectively.
In vitro activity: Inhibition of TRPV4 activity by HC067047 decreased cell migration of HCT-116 and SW620 cells (Fig. 1B). In line with these results, HCT-116 cells exhibited a reduced migration capability at 24 h and 48 h when treated with TRPV4 siRNAs (Fig. 1C and D). Furthermore, this study assessed HCT-116 and SW620 cell invasion using transwells that were coated with Matrigel. The results of the invasion assay indicated that HCT-116 and SW620 cells treated with TRPV4 siRNAs or HC-067047 had a decreased invasion ability when compared with control cells (Fig. 1E and F). Reference: BMC Cancer. 2021 Nov 23;21(1):1264. https://pubmed.ncbi.nlm.nih.gov/34814869/
In vivo activity: Both preventive and therapeutic HC-067047 administration restored Cst (static compliance) and inhibited the increase in total protein, KC and IL-6 levels in BAL fluid in mice, compared to RB (resistive breathing). Preventive TRPV4 inhibition ameliorated the increase in BAL cellularity, while therapeutic TRPV4 inhibition exerted a partial effect. Reference: Int J Chron Obstruct Pulmon Dis. 2022 Feb 15;17:343-353. https://pubmed.ncbi.nlm.nih.gov/35210764/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 20.0 42.42
DMF:PBS (pH 7.2) (1:2) 0.3 0.70
DMSO 51.5 109.30
Ethanol 5.9 12.58

Preparing Stock Solutions

The following data is based on the product molecular weight 471.52 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.

Recalculate based on batch purity %
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. Zhang P, Xu J, Zhang H, Liu XY. Identification of TRPV4 as a novel target in invasiveness of colorectal cancer. BMC Cancer. 2021 Nov 23;21(1):1264. doi: 10.1186/s12885-021-08970-7. PMID: 34814869; PMCID: PMC8611894. 2. Michinaga S, Onishi K, Shimizu K, Mizuguchi H, Hishinuma S. Pharmacological Inhibition of Transient Receptor Potential Vanilloid 4 Reduces Vasogenic Edema after Traumatic Brain Injury in Mice. Biol Pharm Bull. 2021;44(11):1759-1766. doi: 10.1248/bpb.b21-00512. PMID: 34719652. 3. Toumpanakis D, Chatzianastasiou A, Vassilakopoulou V, Mizi E, Dettoraki M, Perlikos F, Giatra G, Mikos N, Theocharis S, Vassilakopoulos T. TRPV4 Inhibition Exerts Protective Effects Against Resistive Breathing Induced Lung Injury. Int J Chron Obstruct Pulmon Dis. 2022 Feb 15;17:343-353. doi: 10.2147/COPD.S336108. PMID: 35210764; PMCID: PMC8857953. 4. Lee WJ, Shim WS. Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus. Front Immunol. 2021 Dec 2;12:772941. doi: 10.3389/fimmu.2021.772941. PMID: 34925342; PMCID: PMC8674573.
In vitro protocol: 1. Zhang P, Xu J, Zhang H, Liu XY. Identification of TRPV4 as a novel target in invasiveness of colorectal cancer. BMC Cancer. 2021 Nov 23;21(1):1264. doi: 10.1186/s12885-021-08970-7. PMID: 34814869; PMCID: PMC8611894. 2. Michinaga S, Onishi K, Shimizu K, Mizuguchi H, Hishinuma S. Pharmacological Inhibition of Transient Receptor Potential Vanilloid 4 Reduces Vasogenic Edema after Traumatic Brain Injury in Mice. Biol Pharm Bull. 2021;44(11):1759-1766. doi: 10.1248/bpb.b21-00512. PMID: 34719652.
In vivo protocol: 1. Toumpanakis D, Chatzianastasiou A, Vassilakopoulou V, Mizi E, Dettoraki M, Perlikos F, Giatra G, Mikos N, Theocharis S, Vassilakopoulos T. TRPV4 Inhibition Exerts Protective Effects Against Resistive Breathing Induced Lung Injury. Int J Chron Obstruct Pulmon Dis. 2022 Feb 15;17:343-353. doi: 10.2147/COPD.S336108. PMID: 35210764; PMCID: PMC8857953. 2. Lee WJ, Shim WS. Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus. Front Immunol. 2021 Dec 2;12:772941. doi: 10.3389/fimmu.2021.772941. PMID: 34925342; PMCID: PMC8674573.

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1: Seki T, Goto K, Kiyohara K, Kansui Y, Murakami N, Haga Y, Ohtsubo T, Matsumura K, Kitazono T. Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca2+-Activated K+ Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension. Hypertension. 2017 Jan;69(1):143-153. PubMed PMID: 27872234.

2: Hong Z, Tian Y, Yuan Y, Qi M, Li Y, Du Y, Chen L, Chen L. Enhanced Oxidative Stress Is Responsible for TRPV4-Induced Neurotoxicity. Front Cell Neurosci. 2016 Oct 17;10:232. PubMed PMID: 27799895; PubMed Central PMCID: PMC5065954.

3: Isogai A, Lee K, Mitsui R, Hashitani H. Functional coupling of TRPV4 channels and BK channels in regulating spontaneous contractions of the guinea pig urinary bladder. Pflugers Arch. 2016 Sep;468(9):1573-85. doi: 10.1007/s00424-016-1863-0. PubMed PMID: 27497848.

4: Yang F, Zhou L, Wang D, Yang LL, Yuan GR, Huang QY. Suppression of TRPV4 channels ameliorates anti-dipsogenic effects under hypoxia in the subfornical organ of rats. Sci Rep. 2016 Jul 20;6:30168. doi: 10.1038/srep30168. PubMed PMID: 27436489; PubMed Central PMCID: PMC4951807.

5: Sakuta H, Nishihara E, Hiyama TY, Lin CH, Noda M. Nax signaling evoked by an increase in [Na+] in CSF induces water intake via EET-mediated TRPV4 activation. Am J Physiol Regul Integr Comp Physiol. 2016 Aug 1;311(2):R299-306. doi: 10.1152/ajpregu.00352.2015. PubMed PMID: 27252474.

6: Murphy TV, Kanagarajah A, Toemoe S, Bertrand PP, Grayson TH, Britton FC, Leader L, Senadheera S, Sandow SL. TRPV3 expression and vasodilator function in isolated uterine radial arteries from non-pregnant and pregnant rats. Vascul Pharmacol. 2016 Aug;83:66-77. doi: 10.1016/j.vph.2016.04.004. PubMed PMID: 27073026.

7: Zhang LP, Kline RH 4th, Deevska G, Ma F, Nikolova-Karakashian M, Westlund KN. Alcohol and high fat induced chronic pancreatitis: TRPV4 antagonist reduces hypersensitivity. Neuroscience. 2015 Dec 17;311:166-79. doi: 10.1016/j.neuroscience.2015.10.028. PubMed PMID: 26480812; PubMed Central PMCID: PMC4670827.

8: Jo AO, Ryskamp DA, Phuong TT, Verkman AS, Yarishkin O, MacAulay N, Križaj D. TRPV4 and AQP4 Channels Synergistically Regulate Cell Volume and Calcium Homeostasis in Retinal Müller Glia. J Neurosci. 2015 Sep 30;35(39):13525-37. doi: 10.1523/JNEUROSCI.1987-15.2015. PubMed PMID: 26424896; PubMed Central PMCID: PMC4588615.

9: Sánchez JC, Rivera RA, Muñoz LV. TRPV4 Channels in Human White Adipocytes: Electrophysiological Characterization and Regulation by Insulin. J Cell Physiol. 2016 Apr;231(4):954-63. doi: 10.1002/jcp.25187. PubMed PMID: 26381274.

10: Shahidullah M, Mandal A, Delamere NA. Damage to lens fiber cells causes TRPV4-dependent Src family kinase activation in the epithelium. Exp Eye Res. 2015 Nov;140:85-93. doi: 10.1016/j.exer.2015.08.013. PubMed PMID: 26318609; PubMed Central PMCID: PMC4763713.

11: Yin J, Michalick L, Tang C, Tabuchi A, Goldenberg N, Dan Q, Awwad K, Wang L, Erfinanda L, Nouailles G, Witzenrath M, Vogelzang A, Lv L, Lee WL, Zhang H, Rotstein O, Kapus A, Szaszi K, Fleming I, Liedtke WB, Kuppe H, Kuebler WM. Role of Transient Receptor Potential Vanilloid 4 in Neutrophil Activation and Acute Lung Injury. Am J Respir Cell Mol Biol. 2016 Mar;54(3):370-83. doi: 10.1165/rcmb.2014-0225OC. PubMed PMID: 26222277.

12: Zou Q, Leung SW, Vanhoutte PM. Transient Receptor Potential Channel Opening Releases Endogenous Acetylcholine, which Contributes to Endothelium-Dependent Relaxation Induced by Mild Hypothermia in Spontaneously Hypertensive Rat but Not Wistar-Kyoto Rat Arteries. J Pharmacol Exp Ther. 2015 Aug;354(2):121-30. doi: 10.1124/jpet.115.223693. PubMed PMID: 26060231.

13: Jie P, Hong Z, Tian Y, Li Y, Lin L, Zhou L, Du Y, Chen L, Chen L. Activation of transient receptor potential vanilloid 4 induces apoptosis in hippocampus through downregulating PI3K/Akt and upregulating p38 MAPK signaling pathways. Cell Death Dis. 2015 Jun 4;6:e1775. doi: 10.1038/cddis.2015.146. PubMed PMID: 26043075; PubMed Central PMCID: PMC4669828.

14: Nayak PS, Wang Y, Najrana T, Priolo LM, Rios M, Shaw SK, Sanchez-Esteban J. Mechanotransduction via TRPV4 regulates inflammation and differentiation in fetal mouse distal lung epithelial cells. Respir Res. 2015 May 27;16:60. doi: 10.1186/s12931-015-0224-4. PubMed PMID: 26006045; PubMed Central PMCID: PMC4446903.

15: Jie P, Tian Y, Hong Z, Li L, Zhou L, Chen L, Chen L. Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice. Front Cell Neurosci. 2015 Apr 10;9:141. doi: 10.3389/fncel.2015.00141. PubMed PMID: 25914628; PubMed Central PMCID: PMC4392311.

16: Peixoto-Neves D, Wang Q, Leal-Cardoso JH, Rossoni LV, Jaggar JH. Eugenol dilates mesenteric arteries and reduces systemic BP by activating endothelial cell TRPV4 channels. Br J Pharmacol. 2015 Jul;172(14):3484-94. doi: 10.1111/bph.13156. PubMed PMID: 25832173; PubMed Central PMCID: PMC4507154.

17: Vizin RC, Scarpellini Cda S, Ishikawa DT, Correa GM, de Souza CO, Gargaglioni LH, Carrettiero DC, Bícego KC, Almeida MC. TRPV4 activates autonomic and behavioural warmth-defence responses in Wistar rats. Acta Physiol (Oxf). 2015 Jun;214(2):275-89. doi: 10.1111/apha.12477. PubMed PMID: 25739906.

18: Zhao PY, Gan G, Peng S, Wang SB, Chen B, Adelman RA, Rizzolo LJ. TRP Channels Localize to Subdomains of the Apical Plasma Membrane in Human Fetal Retinal Pigment Epithelium. Invest Ophthalmol Vis Sci. 2015 Mar 3;56(3):1916-23. doi: 10.1167/iovs.14-15738. PubMed PMID: 25736794; PubMed Central PMCID: PMC4364639.

19: Son GY, Yang YM, Park WS, Chang I, Shin DM. Hypotonic stress induces RANKL via transient receptor potential melastatin 3 (TRPM3) and vaniloid 4 (TRPV4) in human PDL cells. J Dent Res. 2015 Mar;94(3):473-81. doi: 10.1177/0022034514567196. PubMed PMID: 25595364; PubMed Central PMCID: PMC4814022.

20: Sánchez JC, López-Zapata DF, Wilkins RJ. TRPV4 channels activity in bovine articular chondrocytes: regulation by obesity-associated mediators. Cell Calcium. 2014 Dec;56(6):493-503. doi: 10.1016/j.ceca.2014.10.006. PubMed PMID: 25459300.