Hydralazine hydrochloride 

Hydralazine hydrochloride is an orally active, blood-brain barrier-permeable DNA methyltransferase inhibitor with vasodilatory, arterial smooth muscle relaxant and hypotensive activities. Hydralazine hydrochloride reactivates silenced tumor suppressor genes via mediating DNA demethylation, while exerting neuroprotective and anti-inflammatory properties. Hydralazine hydrochloride inhibits NOS-2 (iNOS) and COX-2, and reduces the production of NO and PGE_E2; meanwhile, Hydralazine hydrochloride scavenges reactive oxygen species and inhibits macrophage activation. Hydralazine hydrochloride alleviates motor dysfunction, neuropathic inflammatory pain, and formalin-induced somatic and emotional pain responses. In addition, Hydralazine hydrochloride directly induces DNA strand breaks and sister chromatid exchange, exhibiting certain mutagenic characteristics. Hydralazine hydrochloride has been widely used in studies on hypertension, various cancers (such as cervical cancer, leukemia), spinal cord injury and the mechanisms of inflammatory pain^{[1][2][3][4][5]}.

Hydralazine hydrochloride (10 μM; 5 days) demethylates and reactivates expression of silenced tumor suppressor genes (ER, RARβ, p16) in MDA-231, MCF-7, and T24 cancer cell lines, respectively^[1].
Hydralazine hydrochloride (10 μM; 24 hours) reduces DNMT1 and DNMT3a mRNA expression in MCF-7 breast cancer cells^[1].
Hydralazine hydrochloride (0.1-10.0 mM) does not impair phagocytic function or viability of thioglycollate-prestimulated rat peritoneal macrophages^[2].
Hydralazine hydrochloride (0.1-10.0 mM) significantly inhibits nitrite production by LPS/IFN-γ-stimulated thioglycollate-prestimulated rat peritoneal macrophages, with an IC₅₀ of 0.43 ± 0.03 mM^[2].
Hydralazine hydrochloride (1.0-10.0 mM) inhibits both NOS-2 and COX-2 protein synthesis in LPS/IFN^γ-stimulated thioglycollate-prestimulated rat peritoneal macrophages^[2].
Hydralazine hydrochloride (3.1-50 nmol, plate incorporation test without S-9 mix; 1 mg per plate, spot test with/without S-9 mix) is a direct-acting, low-potency mutagen that induces mixed genetic mutation mechanisms in Salmonella typhimurium strains TA1535, TA100, TA1537, TA97, and TA98, with highest potency in strain TA97^[3].
Hydralazine hydrochloride (5 mg per spot, spot test; serial twofold dilutions, micromethod assay with/without S-9 mix; 16 h incubation at 37°C) is a direct-acting genotoxin that is preferentially lethal to repair-deficient Escherichia coli strains WP67 and CM871, indicating involvement of recA recombination repair, lexA post-replication repair, and polA repair mechanisms, with no dependence on excision repair systems^[3].
Hydralazine hydrochloride (≤25 μM) significantly mitigates acrolein-mediated cell death in PC12 cells^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Hydralazine hydrochloride (i.p.; daily; 7 d) promotes demethylation of the estrogen receptor gene promoter and reactivates estrogen receptor expression in MDA-MB-231 breast cancer xenografts in nude mice^[1].
Hydralazine hydrochloride (used in combination with valproic acid (HY-10585)) eliminates tumor recurrence of HT1080 fibrosarcoma xenografts in nude mice^[1].
Hydralazine (83 mg/kg; i.p.; once daily; 5 days) hydrochloride induces DNA fragmentation in the liver, kidney and spleen (but not the lung) of mice at 6 hours after the last administration, and the damage is completely repaired at 12 hours post-administration; meanwhile, it moderately increases the sister chromatid exchange rate of mouse bone marrow cells by 33%^[3].
Hydralazine (5 mg/kg; i.p.; twice; 14 d) hydrochloride reduces acrolein levels by 50-70% in the injured spinal cord of rats, decreases post-injury cyst formation by 70%, improves motor function recovery, and alleviates mechanical hyperalgesia in rat models of spinal cord injury^[4].
Hydralazine (0.1-10 mg/kg; i.p.; single dose) hydrochloride dose-dependently alleviates formalin-induced somatic and emotional inflammatory pain in male C57BL/6 mice, with a ED₅₀ of 0.239-1.0160 mg/kg, while inhibiting excessive acrolein production and neuronal activation in the spinal cord^[5].
Hydralazine (10 mg/kg; i.p.; single dose) hydrochloride does not impair central nervous system function in male C57BL/6 mice^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

196.64

C₈H₉ClN₄

304-20-1

Solid

White to off-white

NNC1=NN=CC2=C1C=CC=C2.Cl

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

• [1]. Arce C, et al. Hydralazine target: from blood vessels to the epigenome. J Transl Med. 2006;4:10. Published 2006 Feb 28.  [Content Brief]

  [2]. Leiro JM, et al. Antioxidant activity and inhibitory effects of hydralazine on inducible NOS/COX-2 gene and protein expression in rat peritoneal macrophages. Int Immunopharmacol. 2004;4(2):163-177.  [Content Brief]

  [3]. de Flora S, et al. In vivo and in vitro genotoxicity of three antihypertensive hydrazine derivatives (hydralazine, dihydralazine, and endralazine). Environ Mutagen. 1982;4(5):605-619.  [Content Brief]

  [4]. Park J, et al. Neuroprotective role of hydralazine in rat spinal cord injury-attenuation of acrolein-mediated damage. J Neurochem. 2014;129(2):339-349.  [Content Brief]

  [5]. Bai L, et al. Attenuation of mouse somatic and emotional inflammatory pain by hydralazine through scavenging acrolein and inhibiting neuronal activation. Pain Physician. 2012;15(4):311-326.  [Content Brief]