MedKoo Cat#: 592140 | Name: Proadifen hydrochloride
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Description:

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

Proadifen hydrochloride is an inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.

Chemical Structure

Proadifen hydrochloride
CAS#62-68-0

Theoretical Analysis

MedKoo Cat#: 592140

Name: Proadifen hydrochloride

CAS#: 62-68-0

Chemical Formula: C23H32ClNO2

Exact Mass: 389.2122

Molecular Weight: 389.96

Elemental Analysis: C, 70.84; H, 8.27; Cl, 9.09; N, 3.59; O, 8.21

Price and Availability

Size Price Availability Quantity
100mg USD 280.00
500mg USD 580.00
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Related CAS #
No Data
Synonym
Proadifen hydrochloride; NSC 170997; NSC-170997; NSC170997
IUPAC/Chemical Name
Benzeneacetic acid, alpha-phenyl-alpha-propyl-, 2-(diethylamino)ethyl ester, hydrochloride
InChi Key
FHIKZROVIDCMJA-UHFFFAOYSA-N
InChi Code
InChI=1S/C23H31NO2.ClH/c1-4-17-23(20-13-9-7-10-14-20,21-15-11-8-12-16-21)22(25)26-19-18-24(5-2)6-3;/h7-16H,4-6,17-19H2,1-3H3;1H
SMILES Code
O=C(OCCN(CC)CC)C(CCC)(C1=CC=CC=C1)C2=CC=CC=C2.[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 DMSO
Shelf Life
>3 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
2934.99.03.00
More Info
Product Data
Biological target:
Proadifen hydrochloride is a Cytochrome P450 inhibitor (IC50 = 19μM).
In vitro activity:
The aim of this study therefore was to evaluate the potential anti-proliferative effect of proadifen on HT-29 colon cancer cells. The results show that proadifen inhibited the growth of HT-29 cells by the accumulation of cells in the G1 phase of the cell cycle, reduction of metabolic activity and colony formation and by the induction of apoptosis. Analyses of Western blots and flow cytometry revealed time- and dose-dependent phosphatidylserine externalization, caspase-3 activation and PARP cleavage. Reference: Toxicol In Vitro. 2012 Sep;26(6):775-82. https://pubmed.ncbi.nlm.nih.gov/22683934/
In vivo activity:
The aim of this study was to investigate the effect of SKF525 on the excitability of central catecholamine neurons. Adult male Wistar rats were administered SKF525 forty-eight, twenty-four, and one hour before electrophysiological assessments. It was found that the SKF525 enhanced the excitability of noradrenaline and reduced the excitability of dopamine neurons. This study suggests that corticosterone-induced inhibition of 5-HT neurons underlines, at least in part, the ability of SKF525 to stimulate noradrenaline neurons. The inhibitory effect of SKF525 on dopamine neurons might be in turn secondary to the stimulatory effect of this compound on noradrenaline neurons. Reference: Gen Physiol Biophys. 2022 May;41(3):255-262. https://pubmed.ncbi.nlm.nih.gov/35616005/
Solvent mg/mL mM comments
Solubility
DMF 25.0 64.11
DMSO 35.0 89.75
Ethanol 20.0 51.29
PBS (pH 7.2) 0.1 0.36
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 389.96 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. Jendželovský R, Koval J, Mikeš J, Papčová Z, Plšíková J, Fedoročko P. Inhibition of GSK-3β reverses the pro-apoptotic effect of proadifen (SKF-525A) in HT-29 colon adenocarcinoma cells. Toxicol In Vitro. 2012 Sep;26(6):775-82. doi: 10.1016/j.tiv.2012.05.014. Epub 2012 Jun 7. PMID: 22683934. 2. Morris DD, Moore JN, Wiltshire N, Fischer K. Proadifen-induced production of prostacyclin by equine peritoneal macrophages. Am J Vet Res. 1989 May;50(5):747-50. PMID: 2499232. 3. Paliokha R, Grinchii D, Khoury T, Nejati Bervanlou R, Dremencov E. Inhibition of cytochrome P450 with proadifen alters the excitability of brain catecholamine-secreting neurons. Gen Physiol Biophys. 2022 May;41(3):255-262. doi: 10.4149/gpb_2022017. PMID: 35616005. 4. Ohhira S, Matsui H, Watanabe K. Effects of pretreatment with SKF-525A on triphenyltin metabolism and toxicity in mice. Toxicol Lett. 2000 Nov 20;117(3):145-50. doi: 10.1016/s0378-4274(00)00255-1. PMID: 11087980.
In vitro protocol:
1. Jendželovský R, Koval J, Mikeš J, Papčová Z, Plšíková J, Fedoročko P. Inhibition of GSK-3β reverses the pro-apoptotic effect of proadifen (SKF-525A) in HT-29 colon adenocarcinoma cells. Toxicol In Vitro. 2012 Sep;26(6):775-82. doi: 10.1016/j.tiv.2012.05.014. Epub 2012 Jun 7. PMID: 22683934. 2. Morris DD, Moore JN, Wiltshire N, Fischer K. Proadifen-induced production of prostacyclin by equine peritoneal macrophages. Am J Vet Res. 1989 May;50(5):747-50. PMID: 2499232.
In vivo protocol:
1. Paliokha R, Grinchii D, Khoury T, Nejati Bervanlou R, Dremencov E. Inhibition of cytochrome P450 with proadifen alters the excitability of brain catecholamine-secreting neurons. Gen Physiol Biophys. 2022 May;41(3):255-262. doi: 10.4149/gpb_2022017. PMID: 35616005. 2. Ohhira S, Matsui H, Watanabe K. Effects of pretreatment with SKF-525A on triphenyltin metabolism and toxicity in mice. Toxicol Lett. 2000 Nov 20;117(3):145-50. doi: 10.1016/s0378-4274(00)00255-1. PMID: 11087980.
1: Grinchii D, Paliokha R, Tseilikman V, Dremencov E. Inhibition of cytochrome P450 by proadifen diminishes the excitability of brain serotonin neurons in rats. Gen Physiol Biophys. 2018 Sep;37(6):711-713. doi: 10.4149/gpb_2018040. Epub 2018 Nov 15. PMID: 30431437. 2: Liu DX, Zhao MM. [Determination of Methcathinone in Urine by GC-MS]. Fa Yi Xue Za Zhi. 2017 Oct;33(5):506-508. Chinese. doi: 10.3969/j.issn.1004-5619.2017.05.012. Epub 2017 Oct 25. PMID: 29275556. 3: Sykes BG, Van Steyn PM, Vignali JD, Winalski J, Lozier J, Bell WE, Turner JE. The Relationship between Estrogen and Nitric Oxide in the Prevention of Cardiac and Vascular Anomalies in the Developing Zebrafish (Danio Rerio). Brain Sci. 2016 Oct 26;6(4):51. doi: 10.3390/brainsci6040051. PMID: 27792175; PMCID: PMC5187565. 4: Hu G, Li X, Zhang S, Wang X. Association of rat thoracic aorta dilatation by astragaloside IV with the generation of endothelium-derived hyperpolarizing factors and nitric oxide, and the blockade of Ca2+ channels. Biomed Rep. 2016 Jul;5(1):27-34. doi: 10.3892/br.2016.680. Epub 2016 May 18. PMID: 27347401; PMCID: PMC4907089. 5: Huang YC, Han YS. Determining anti-betanodavirus compounds through a GF-1 cell-based screening platform. Antiviral Res. 2014 May;105:47-53. doi: 10.1016/j.antiviral.2014.02.018. Epub 2014 Feb 28. PMID: 24583156. 6: Smith GB, Bend JR, Bedard LL, Reid KR, Petsikas D, Massey TE. Biotransformation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in peripheral human lung microsomes. Drug Metab Dispos. 2003 Sep;31(9):1134-41. doi: 10.1124/dmd.31.9.1134. PMID: 12920169. 7: Kitamura S, Shimizu Y, Shiraga Y, Yoshida M, Sugihara K, Ohta S. Reductive metabolism of p,p'-DDT and o,p'-DDT by rat liver cytochrome P450. Drug Metab Dispos. 2002 Feb;30(2):113-8. doi: 10.1124/dmd.30.2.113. PMID: 11792678. 8: Jin ZY, Gu MS, Luo Y. [Quantitative analysis of soporific sedative drugs and local anesthetic drugs with unidentical standard substance by GC-AED]. Yao Xue Xue Bao. 1997 Nov;32(11):865-8. Chinese. PMID: 11596207. 9: Szotáková B, Wsól V, Skálová L, Kvasnicková E. Role of cytochrome P4501A in biotransformation of the potential anticancer drug oracin. Exp Toxicol Pathol. 1999 Jul;51(4-5):428-31. doi: 10.1016/S0940-2993(99)80034-7. PMID: 10445410. 10: Eissa FZ, Qualls CW Jr, Burrows GE, Lish JW. Effects of feeding Artemisia filifolia and Helenium flexuosum on rabbit cytochrome P450 isozymes. Vet Hum Toxicol. 1996 Feb;38(1):19-23. PMID: 8825743. 11: Robertson IG, Bland TJ. Inhibition by SKF-525A of the aldehyde oxidase- mediated metabolism of the experimental antitumour agent acridine carboxamide. Biochem Pharmacol. 1993 May 25;45(10):2159-62. doi: 10.1016/0006-2952(93)90031-q. PMID: 8512597. 12: Engberg G, Elebring T, Nissbrandt H. Deprenyl (selegiline), a selective MAO-B inhibitor with active metabolites; effects on locomotor activity, dopaminergic neurotransmission and firing rate of nigral dopamine neurons. J Pharmacol Exp Ther. 1991 Nov;259(2):841-7. PMID: 1658311. 13: Ross SB. Further studies on the high-affinity binding of 3H-alaproclate to membranes from rat liver and some other tissues. Pharmacol Toxicol. 1990 Mar;66(3):170-5. doi: 10.1111/j.1600-0773.1990.tb00727.x. PMID: 2333272. 14: Morris DD, Moore JN, Wiltshire N, Fischer K. Proadifen-induced production of prostacyclin by equine peritoneal macrophages. Am J Vet Res. 1989 May;50(5):747-50. PMID: 2499232. 15: Rossi M, Markovitz S, Callahan T. Defining the active site of cytochrome P-450: the crystal and molecular structure of an inhibitor, SKF-525A. Carcinogenesis. 1987 Jul;8(7):881-7. doi: 10.1093/carcin/8.7.881. PMID: 3594722. 16: Taylor RW, Greutink C, Jain NC. Identification of underivatized basic drugs in urine by capillary column gas chromatography. J Anal Toxicol. 1986 Sep- Oct;10(5):205-8. doi: 10.1093/jat/10.5.205. PMID: 3773481. 17: Green J, Large PJ. Subcellular localization and properties of partially purified dimethylamine and trimethylamine mono-oxygenase activities in Candida utilis. J Gen Microbiol. 1984 Oct;130(10):2577-88. doi: 10.1099/00221287-130-10-2577. PMID: 6542583. 18: Green J, Large PJ. Oxidation of dimethylamine and trimethylamine in methazotrophic yeasts by microsomal mono-oxygenases sensitive to carbon monoxide. Biochem Biophys Res Commun. 1983 Jun 29;113(3):900-7. doi: 10.1016/0006-291x(83)91084-7. PMID: 6870901. 19: Brookman S, Kourounakis P. Effect of pregnenolone-16 alpha-carbonitrile on the biliary and urinary excretion of imipramine and some of its metabolites in rats. Arzneimittelforschung. 1982;32(10):1298-301. PMID: 6891231. 20: Sylvester JT, McGowan C. The effects of agents that bind to cytochrome P-450 on hypoxic pulmonary vasoconstriction. Circ Res. 1978 Sep;43(3):429-37. doi: 10.1161/01.res.43.3.429. PMID: 679425.