[CAS NO. 99-66-1] Valproic acid
PRODUCTS SPECIFICATIONS [99-66-1]
DESCRIPTION [99-66-1]
Overview
| MDL | MFCD00002672 |
|---|---|
| Molecular Weight | 144.21 |
| Molecular Formula | C8H16O2 |
| SMILES | CCCC(CCC)C(O)=O |
24 Publications Citing Use of MCE
- [1]Sci Adv. 2021 Aug 11;7(33):eabf4416.
- [2]Biomaterials. 2018 Dec 6;193:30-46.
- [3]EMBO J. 2021 Apr 28;e106771.
- [4]Oncogene. 2021 Apr;40(15):2711-2724.
- [5]Sci Total Environ. 2021, 147014.
- [6]Acta Pharmacol Sin. 2020 Jun 17.
- [7]Ecotoxicol Environ Saf. 2022 Jun 14;241:113752.
- [8]Biotechnol Bioeng. 2021 Sep 3.
- [9]Phytomedicine. 19 August 2022, 154403.
- [10]J Biol Chem. 2023 Jan 31;102971.
- [11]Sci Rep. 2020 Sep 16;10(1):15201.
- [12]Toxicol Lett. 2021 Apr 24;346:47-56.
- [13]Biochim Biophys Acta Gene Regul Mech. 2020 Sep;1863(9):194597.
- [14]Clin Dev Immunol. 2020 Aug 4;2020:4384696.
- [15]BMC Cancer. 2022 Aug 8;22(1):864.
- [16]Biochem Biophys Res Commun. 2022.
- [17]J Interferon Cytokine Res. 2021 Dec;41(12):439-449.
- [18]Lett Drug Des Discover. 2019 Nov.
- [19]STAR Protoc. 16 September 2022, 101638.
- [20]Research Square Preprint. 2022 Jul.
- [21]Brain Science Advances. 2022 Feb.
- [22]Research Square Preprint. 2022 Jan.
- [23]Mil Med Res. 2020 Nov 1;7(1):52.
- [24]Mil Med Res. 2020 Sep 6;7(1):42.
Summary
Valproic acid (VPA) is an orally active HDAC inhibitor, with IC 50 in the range of 0.5 and 2 mM, also inhibits HDAC1 ( IC 50 , 400 μM), and induces proteasomal degradation of HDAC2 . Valproic acid activates Notch1 signaling and inhibits proliferation in small cell lung cancer (SCLC) cells. Valproic acid is used in the treatment of epilepsy, bipolar disorder, metabolic disease , HIV infection and prevention of migraine headaches [1] [2] [3] [4] [5] [6] [7] .
IC50 & Target
|
HDAC1 400 μM (IC 50 ) |
HDAC 0.5-2 mM (IC 50 ) |
HDAC2
|
Autophagy
|
Mitophagy
|
In Vitro
Valproic acid (VPA) (0-15 mM; 24 and 72 h) inhibits Hela cell growth in a dose- and time- dependent manner
[1]
.
Valproic acid (10 mM; 24 h) significantly attenuates the activities of total, cytosol and nuclear HDACs
[1]
.
Valproic acid (0-15 mM; 24 h) induces a G1 phase arrest at 1–3 mM and a G2/M phase arrest at 10 mM, and increases the percentage of sub-G1 cells in HeLa cells. Valproic acid also induces necrosis, apoptosis and lactate dehydrogenase (LDH) release
[1]
.
Valproic acid (0-20 mM; 24 h) activates Tcf/Lef-dependent transcription and synergizes with lithium
[2]
.
Valproic acid (0-5 mM; 0-18 h) increases β-catenin levels in Neuro2A cells
[2]
.
Valproic acid (0-2 mM; 0-24 h) stimulates phosphorylation of AMPK and ACC in hepatocytes
[5]
.
Valproic acid (0-10 mM; 2 days) induces Notch1 signaling and morphologic differentiation, suppresses production of NE tumor markers in SCLC cells
[6]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [1]
| Cell Line: | HeLa cells |
| Concentration: | 0, 1, 3, 5, 10 and 15 mM |
| Incubation Time: | 24 and 72 h |
| Result: | HeLa cell growth was dose- and time-dependently decreased with an IC 50 of ~10 and 4 mM at 24 and 72 h. |
Western Blot Analysis [1] [2] [5]
| Cell Line: | HeLa cells, Neuro2A cells or primary mouse hepatocytes |
| Concentration: | 10 mM (HeLa); 0, 2, and 5 mM (Neuro2A); 0.2, 0.4, 0.8, 1.2 and 2 mM (hepatocytes) |
| Incubation Time: | 10 mM (HeLa); 0, 2, and 5 mM (Neuro2A); 0.2, 0.4, 0.8, 1.2 and 2 Mm (hepatocytes) |
| Result: |
Increased the form of acetylated histone 3.
Reduced PARP, induced cleavage PARP, and downregulated Bcl-2. Increased β-catenin levels. Increased the phosphorylation of AMPK and ACC. |
Cell Cycle Analysis [1]
| Cell Line: | HeLa cells |
| Concentration: | 0, 1, 3, 5, 10 and 15 mM |
| Incubation Time: | 24 h |
| Result: | Induced a G1 phase arrest at 1–3 mM, significantly induced a G2/M phase arrest at 10 mM, and increased the percentage of sub-G1 cells in HeLa cells in a dose-dependent manner at 24 h. |
In Vivo
Valproic acid (VPA) (500 mg/kg; i.p.; daily for 12 days) inhibits tumor angiogenesis in mice transplanted with Kasumi-1 cells
[3]
.
Valproic acid (350 mg/kg; i.p.; once) enhances social behavior in rats
[4]
.
Valproic acid (0.26% (w/v); p.o. via drinking water; 14 days) decreases liver mass, hepatic fat accumulation, and serum glucose in obese mice without hepatotoxicity
[5]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Female BALB/c nude mice, Kasumi-1 tumor model [3] |
| Dosage: | 500 mg/kg |
| Administration: | Intraperitoneal injection, daily for 12 days |
| Result: |
Inhibited tumor growth and tumor angiogenesis.
Inhibited the mRNA and protein expression of VEGF, VEGFR2 and bFGF. Inhibited HDAC activity and increased acetylation of histone H3. Enhanced the accumulation of hyperacetylated histone H3 on VEGF promoters. |
| Animal Model: | Timed-pregnant Long Evans rats [4] |
| Dosage: | 350 mg/kg |
| Administration: | Intraperitoneal injection, once |
| Result: | Demonstrated more social investigation and play fighting than control animals. |
| Animal Model: | Obese phenotype of ob/ob mice [5] |
| Dosage: | 0.26% (w/v) |
| Administration: | Oral via drinking water, 14 days |
| Result: | Revealed a marked reduction in the accumulation of fats in the liver as compared with the untreated mice, significantly decreased liver mass to body mass, decreased serum triglyceride concentrations, and did not induce hepatotoxicity. |
Appearance
Liquid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Pure form | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 693.43 mM ; Need ultrasonic)
H 2 O : 1 mg/mL ( 6.93 mM ; Need ultrasonic and warming)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 6.9343 mL | 34.6717 mL | 69.3433 mL |
| 5 mM | 1.3869 mL | 6.9343 mL | 13.8687 mL |
| 10 mM | 0.6934 mL | 3.4672 mL | 6.9343 mL |
-
1.
Add each solvent one by one: PBS
Solubility: 100 mg/mL (693.43 mM); Clear solution; Need ultrasonic and warming and heat to 60°C
-
2.
Add each solvent one by one: 0.5% CMC/saline water
Solubility: 20 mg/mL (138.69 mM); Suspended solution; Need ultrasonic
-
3.
-
4.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (17.34 mM); Clear solution
-
5.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (17.34 mM); Clear solution
References
- [1] Han BR, et al. Valproic acid inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis. Oncol Rep. 2013 Dec;30(6):2999-3005.
- [2] Valproic acid, et al. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem. 2001 Sep 28;276(39):36734-41.
- [3] Zhang ZH, et al. Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi 1 leukemia cells. Mol Med Rep. 2013 Nov 28.
- [4] Cohen OS, et al. Acute prenatal exposure to a moderate dose of valproic acid increases social behavior and alters gene expression in rats. Int J Dev Neurosci. 2013 Dec;31(8):740-50.
- [5] Avery LB, et al. Valproic Acid Is a Novel Activator of AMP-Activated Protein Kinase and Decreases Liver Mass, Hepatic Fat Accumulation, and Serum Glucose in Obese Mice. Mol Pharmacol. 2014 Jan;85(1):1-10.
- [6] Platta CS, et al. Valproic acid induces Notch1 signaling in small cell lung cancer cells. J Surg Res. 2008 Jul;148(1):31-7.
- [7] Routy JP, et al. Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study. HIV Med. 2012 May;13(5):291-6.
Synonyms