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MedKoo Cat#: 526642 | Name: EVP-4593
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Description:

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

EVP4593, also known as QNZ and CAY10470, is an inhibitor of NF-κB activation with an IC50 of 11 nM in human Jurkat cells. EVP4593 reduced the number of lysosomes/autophagosomes and SOC currents in HD GMSLNs and exerted neuroprotective effects during cell aging. EVP4593 may be a promising anti-HD drug.

Chemical Structure

EVP-4593
EVP-4593
CAS#545380-34-5

Theoretical Analysis

MedKoo Cat#: 526642

Name: EVP-4593

CAS#: 545380-34-5

Chemical Formula: C22H20N4O

Exact Mass: 356.1637

Molecular Weight: 356.43

Elemental Analysis: C, 74.14; H, 5.66; N, 15.72; O, 4.49

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 2,450.00 Ready to ship
1g USD 3,450.00 Ready to ship
2g USD 5,950.00 Ready to ship
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Related CAS #
No Data
Synonym
CAY10470; CAY-10470; CAY 10470; QNZ; EVP4593; EVP 4593; EVP-4593.
IUPAC/Chemical Name
N4-(4-phenoxyphenethyl)quinazoline-4,6-diamine
InChi Key
IBAKVEUZKHOWNG-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H20N4O/c23-17-8-11-21-20(14-17)22(26-15-25-21)24-13-12-16-6-9-19(10-7-16)27-18-4-2-1-3-5-18/h1-11,14-15H,12-13,23H2,(H,24,25,26)
SMILES Code
NC1=CC2=C(N=CN=C2NCCC3=CC=C(OC4=CC=CC=C4)C=C3)C=C1
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, not 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
Biological target:
QNZ (EVP4593) is a neuroprotective inhibitor of SOC channel that shows strong inhibitory effects on NF-κB transcriptional activation and TNF-α production with IC50s of 11 and 7 nM, respectively
In vitro activity:
The aim of this study was to investigate whether QNZ mediates oxidative stress and inflammation contributed to IL-1β-induced nucleus pulposus (NP) cells degeneration in vitro. NP were isolated cells from human disc samples collected from patients and the IL1β-induced NP cells degenerated model was constructed. The cells were randomly divided into 3 groups, namely, Control group, IL1β group (10 µM), QNZ + IL-1β group (containing 10 nM QNZ and 10 µM IL-1β). This study showed that IL-1β promoted the progress of IDD, with markedly increased expressions of collagen I, p16, p53, and β-gal, as well as decreased expressions of collagen II and aggrecan. However, QNZ treatment could reverse the effects of IL-1β. It was found that cell proliferation was increased, ROS level was decreased, antioxidant enzymes were upregulated, and inflammatory factors were reduced after QNZ stimulation. Moreover, NF-κB/MAPKs signaling proteins IKKβ, IκBα, p65, ERK, JNK, and p38 were significantly dephosphorylated by QNZ. These results indicated that QNZ prevented NP degradation via restraining oxidative stress and inflammation through inhibition of the NFκB/MAPKs signaling pathway. QNZ may become a novel insight into the therapy of IVDD in the future. Reference: Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):2077-2086. https://pubmed.ncbi.nlm.nih.gov/32141577/
In vivo activity:
To further evaluate potential neuroprotective effects of EVP4593, it was tested in vivo with YAC128 mice and WT controls. an osmotic minipump loaded with 200 μl of EVP4593 (0.25 mg/ml) was used to infuse EVP4593 into the ventricles of 10.5-month-old WT and YAC128 mice over 6 weeks. the MSN spine density in EVP4593-treated WT mice was 13.04 ± 0.57 spines/10 μm (n = 32 neurons from 3 mice), significantly lower than in vehicle-treated WT mice (p = 0.0007; Fig. 11D). Also consistent with Figures 9 and 11, nSOC inhibition restored the YAC128 MSN spine density to WT levels (Fig. 11C). The spine density in EVP4593-treated YAC128 mice was 14.64 ± 0.57 spines/10 μm (n = 36 neurons from 6 mice). These data support an important role for nSOC in MSN spine maintenance and suggest that supranomal nSOC leads to spine destabilization in YAC128 MSNs in vivo. It has been demonstrated that EVP4593 reduces synaptic nSOC and rescues spine loss in YAC128 MSNs. Intraventricular delivery of EVP4593 in YAC128 mice rescued age-dependent striatal spine loss in vivo. The results suggest EVP4593 and other inhibitors of the STIM2dependent nSOC pathway as promising leads for HD (Huntington’s disease) therapeutic development. Reference: J Neurosci. 2016 Jan 6;36(1):125-41. doi: 10.1523/JNEUROSCI.1038-15.2016 https://pubmed.ncbi.nlm.nih.gov/26740655/
Solvent mg/mL mM comments
Solubility
DMSO 43.0 120.64
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 356.43 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. Zhu SB, Xu YQ, Gao H, Deng Y. NF-κB inhibitor QNZ protects human chondrocyte degeneration by promoting glucose uptake through Glut4 activation. Eur Rev Med Pharmacol Sci. 2020 May;24(9):4642-4651. doi: 10.26355/eurrev_202005_21150. PMID: 32432727. 2. Chen ZB, Yu YB, Wa QB, Zhou JW, He M, Cen Y. The role of quinazoline in ameliorating intervertebral disc degeneration by inhibiting oxidative stress and anti-inflammation via NF-κB/MAPKs signaling pathway. Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):2077-2086. doi: 10.26355/eurrev_202002_20387. PMID: 32141577. 3. . Shi CX, Jin J, Wang XQ, Song T, Li GH, Li KZ, Ma JH. Sevoflurane attenuates brain damage through inhibiting autophagy and apoptosis in cerebral ischemia‑reperfusion rats. Mol Med Rep. 2020 Jan;21(1):123-130. doi: 10.3892/mmr.2019.10832. Epub 2019 Nov 20. PMID: 31746402; PMCID: PMC6896401. 4. Wu J, Ryskamp DA, Liang X, Egorova P, Zakharova O, Hung G, Bezprozvanny I. Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington's Disease Mouse Model. J Neurosci. 2016 Jan 6;36(1):125-41. doi: 10.1523/JNEUROSCI.1038-15.2016. PMID: 26740655; PMCID: PMC4701955.
In vitro protocol:
1. Zhu SB, Xu YQ, Gao H, Deng Y. NF-κB inhibitor QNZ protects human chondrocyte degeneration by promoting glucose uptake through Glut4 activation. Eur Rev Med Pharmacol Sci. 2020 May;24(9):4642-4651. doi: 10.26355/eurrev_202005_21150. PMID: 32432727. 2. Chen ZB, Yu YB, Wa QB, Zhou JW, He M, Cen Y. The role of quinazoline in ameliorating intervertebral disc degeneration by inhibiting oxidative stress and anti-inflammation via NF-κB/MAPKs signaling pathway. Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):2077-2086. doi: 10.26355/eurrev_202002_20387. PMID: 32141577.
In vivo protocol:
1. Shi CX, Jin J, Wang XQ, Song T, Li GH, Li KZ, Ma JH. Sevoflurane attenuates brain damage through inhibiting autophagy and apoptosis in cerebral ischemia‑reperfusion rats. Mol Med Rep. 2020 Jan;21(1):123-130. doi: 10.3892/mmr.2019.10832. Epub 2019 Nov 20. PMID: 31746402; PMCID: PMC6896401. 2. Wu J, Ryskamp DA, Liang X, Egorova P, Zakharova O, Hung G, Bezprozvanny I. Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington's Disease Mouse Model. J Neurosci. 2016 Jan 6;36(1):125-41. doi: 10.1523/JNEUROSCI.1038-15.2016. PMID: 26740655; PMCID: PMC4701955.
1: Nekrasov ED, Vigont VA, Klyushnikov SA, Lebedeva OS, Vassina EM, Bogomazova AN, Chestkov IV, Semashko TA, Kiseleva E, Suldina LA, Bobrovsky PA, Zimina OA, Ryazantseva MA, Skopin AY, Illarioshkin SN, Kaznacheyeva EV, Lagarkova MA, Kiselev SL. Manifestation of Huntington's disease pathology in human induced pluripotent stem cell-derived neurons. Mol Neurodegener. 2016 Apr 14;11:27. doi: 10.1186/s13024-016-0092-5. PubMed PMID: 27080129; PubMed Central PMCID: PMC4832474. 2: Wu J, Ryskamp DA, Liang X, Egorova P, Zakharova O, Hung G, Bezprozvanny I. Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington's Disease Mouse Model. J Neurosci. 2016 Jan 6;36(1):125-41. doi: 10.1523/JNEUROSCI.1038-15.2016. PubMed PMID: 26740655; PubMed Central PMCID: PMC4701955. 3: Vigont V, Kolobkova Y, Skopin A, Zimina O, Zenin V, Glushankova L, Kaznacheyeva E. Both Orai1 and TRPC1 are Involved in Excessive Store-Operated Calcium Entry in Striatal Neurons Expressing Mutant Huntingtin Exon 1. Front Physiol. 2015 Nov 24;6:337. doi: 10.3389/fphys.2015.00337. eCollection 2015. PubMed PMID: 26635623; PubMed Central PMCID: PMC4656824. 4: Korzhova VV, Artamonov DN, Vlasova OL, Bezprozvannyĭ IB. [Huntington's disease: cellular and molecular basis of pathology]. Zh Vyssh Nerv Deiat Im I P Pavlova. 2014 Jul-Aug;64(4):359-75. Review. Russian. PubMed PMID: 25723022. 5: Wu J, Shih HP, Vigont V, Hrdlicka L, Diggins L, Singh C, Mahoney M, Chesworth R, Shapiro G, Zimina O, Chen X, Wu Q, Glushankova L, Ahlijanian M, Koenig G, Mozhayeva GN, Kaznacheyeva E, Bezprozvanny I. Neuronal store-operated calcium entry pathway as a novel therapeutic target for Huntington's disease treatment. Chem Biol. 2011 Jun 24;18(6):777-93. doi: 10.1016/j.chembiol.2011.04.012. PubMed PMID: 21700213; PubMed Central PMCID: PMC3124661.