HC-070 is a novel and potent inhibitor of TRPC4 and TRPC5 with IC50s of 9.3 nM and 46 nM for hTRPC5 and hTRPC4 in cell assay. It can lead to anxiolytic and antidepressant effects in mice.

Physicochemical Properties

Molecular Formula	C22H20CL2N4O4
Molecular Weight	475.32460308075
Exact Mass	474.086
CAS #	1628291-95-1
PubChem CID	85473309
Appearance	White to off-white solid powder
LogP	4
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	7
Heavy Atom Count	32
Complexity	678
Defined Atom Stereocenter Count	0
SMILES	N1(CC2=CC=C(Cl)C=C2)C2=C(N(C)C(=O)N(CCCO)C2=O)N=C1OC1=CC=CC(Cl)=C1
InChi Key	VYJPVPHNGWEIBT-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H20Cl2N4O4/c1-26-19-18(20(30)27(22(26)31)10-3-11-29)28(13-14-6-8-15(23)9-7-14)21(25-19)32-17-5-2-4-16(24)12-17/h2,4-9,12,29H,3,10-11,13H2,1H3
Chemical Name	7-(4-Chlorobenzyl)-8-(3-chlorophenoxy)-1-(3-hydroxypropyl)-3-methyl-3,7-dihydro-1H-purine-2,6-dione
Synonyms	HC-070 HC070 HC 070
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	The IC50s of HC-070, a TRPC4/TRPC5 antagonist, are 9.3 nM for hTRPC5 and 46 nM for hTRPC4 respectively. HC-070 is at least 400 times more selective for channels containing human TRPC4 and TRPC5 than for other channels studied, and it modestly inhibits TRPC3 (IC50, 1 μM). With an IC50 of 0.52 nM, 0.55 nM, and 0.32 nM, respectively, HC-070 blocks lanthanum-activated hTRPC5-, mTRPC5-, and rTRPC5-mediated currents in whole-cell manual patch clamp. Furthermore, HC-070 inhibits human TRPC1/TRPC4 channels triggered by M2R at an IC50 of 1.3 nM, as well as human TRPC1/5 channels activated by La3+ and M1R at IC50s of 1.4 nM and 4.4 nM. Human TRPC5 currents stimulated by muscarinic type 1 (M1R) are inhibited by HC-070, with an IC50 of 2.0 nM. With an IC50 of 0.49 nM, HC-070 also inhibits hTRPC4 current via M2R. Amygdala slices' CCK-4-evoked neuronal activity is decreased by HC-070 (20 nM) [1].
ln Vivo	Mice with elevated anxiety-induced (CCK-4) are affected by HC-070 (1 mg/kg, p.o. ), but not in the absence of CCK-4. In a typical EPM, HC-070 (0.3, 1 or 3 mg/kg, oral) lowers anxiety (moderate to high anxiety). In mice subjected to prolonged social stress, HC-070 (1 mg/kg) lowers heightened fear memory performance on days 1–15. Moreover, HC-070 (1, 3, 10 mg/kg, orally) decreased the behavior of burying marbles. In the tail suspension test, HC-070 (0.3, 1, 3, 10 mg/kg, oral) also shortens the duration of immobility, but it has no effect on mice's locomotor activity [1].
References	[1]. Treatment with HC-070, a potent inhibitor of TRPC4 and TRPC5, leads to anxiolytic and antidepressant effects in mice. PLoS One. 2018 Jan 31;13(1):e0191225.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 62.5 mg/mL (~131.49 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1038 mL	10.5192 mL	21.0385 mL
	5 mM	0.4208 mL	2.1038 mL	4.2077 mL
	10 mM	0.2104 mL	1.0519 mL	2.1038 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.