DC Chemicals Limited
China
Product Name: Inauhzin
Price: $375.0/100mg $750.0/250mg $1500.0/1g
Purity: 98.0%
Stocking Period: 3 Day
Contact: Tony Cao

309271-94-1

309271-94-1 structure

309271-94-1 structure

Name: Inauhzin
Chemical Name: 10-[2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)butanoyl]-10H-phenothiazine
CAS Number: 309271-94-1
Molecular Formula: C₂₅H₁₉N₅OS₂
Molecular Weight: 469.581
Catalog: Signaling Pathways Apoptosis MDM-2/p53
Create Date: 2018-06-12 17:17:53
Modify Date: 2024-01-02 11:07:24
Inauhzin is a dual SirT1/IMPDH2 inhibitor, and acts as an activator p53, used in the research of cancer.

Name	10-[2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)butanoyl]-10H-phenothiazine
Synonyms	10-[2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)butanoyl]-10H-phenothiazine 1-Butanone, 1-(10H-phenothiazin-10-yl)-2-(5H-1,2,4-triazino[5,6-b]indol-3-ylthio)- 1-(10H-Phenothiazin-10-yl)-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)-1-butanone Inauhzin

Description	Inauhzin is a dual SirT1/IMPDH2 inhibitor, and acts as an activator p53, used in the research of cancer.
Related Catalog	Signaling Pathways >> Apoptosis >> MDM-2/p53 Signaling Pathways >> Cell Cycle/DNA Damage >> Sirtuin Signaling Pathways >> Epigenetics >> Sirtuin Research Areas >> Cancer
Target	SIRT1 MDM-2/p53 IMPDH2
In Vitro	Inauhzin (10 µM) induces p53 levels as effectively as actinomycin D (10 nM), and mediates p53-dependent cytotoxicity through its specific functional groups in human lung carcinoma H460 cells. Inauhzin (2 µM) induces p53 level and activity as well as p53-dependent apoptosis. Inauhzin also stabilizes p53 and inhibits its ubiquitylation. Inauhzin induces acetylation of p53 in H460 cells, but not tubulin, which is affected by knockdown of SIRT1[1]. Inauhzin (0-2 µM) significantly enhances the expression level and activity of p53 in HCT116p53+/+ cells and enhances the expression level and activity of p53 in H460 cells in a dose-dependent manner. Inauhzin and Nutlin-3 demonstrate synergistic cytotoxicity in the Nutlin-3 low-sensitive cells. Inauhzin and Nutlin-3 synergistically induce p53-dependent apoptosis[2]. Inauhzin targets both SirT1 and IMP dehydrogenase 2 (IMPDH2), and acts as a potent p53 activator[3].
In Vivo	Inauhzin (30 mg/kg, i.p.) effectively induces apoptosis and suppresses tumour growth of H460 xenograft harbouring p53[1]. Inauhzin (30 mg/kg, i.p.) reduces the HCT116 tumor volume by appr 70%. Inauhzin (15 mg/kg) in combination with 150 mg/kg of Nutlin-3 demonstrates a significant synergy on p53 induction, apoptosis and tumor suppression of HCT116p53+/+ xenografts[2].
Cell Assay	The cell counting kit is used to assess cell growth. Cell suspensions are seeded at 5000 cells per well in 96-well culture plates and incubated overnight at 37°C. Compounds are added into the plates and incubated at 37°C for 72 h. Cell growth inhibition is determined by adding WST-8 at a final concentration of 10% to each well, and the absorbance of the samples is measured at 450 nm using a Microplate Reader[1].
Animal Admin	Five-weeks-old female SCID mice are housed in a BSL2 environment. Mice are subcutaneously inoculated with 5×106 H460 or 3×106 HCT116 cells. Tumour growth is monitored every other day with electronic digital calipers in two dimensions. Tumour volume is calculated with the formula: tumour volume (mm3) = (length × width2)/2. When the mean tumour volume reaches approximately 100 mm3 after 7-9 days, animals are dosed by i.p. injection with vehicle (5% DMSO) or Inauhzin. Inhibition of tumour growth is calculated on the last day of treatment. To detect p53 activation in vivo, tumours are harvested and disrupted in RIPA buffer containing a protease inhibitor mixture. Tumour lysates are analysed by IB. Cell proliferation in tumours is assessed by BrdU labeling followed by Immunostaining. 200 mg/kg body weight of BrdU is administrated to mice via i.p. injection 2 h before mice are sacrificed. Apoptosis is examined by TUNEL staining, using the Fluorescein In situ cell death detection kit[1].
References	[1]. Zhang Q, et al. A small molecule Inauhzin inhibits SIRT1 activity and suppresses tumour growth through activation of p53. EMBO Mol Med. 2012 Apr;4(4):298-312. [2]. Zhang Y, et al. Inauhzin and Nutlin3 synergistically activate p53 and suppress tumor growth. Cancer Biol Ther. 2012 Aug;13(10):915-24. [3]. Nguyen D, et al. Reviving the guardian of the genome: Small molecule activators of p53. Pharmacol Ther. 2017 Oct;178:92-108.

Density	1.5±0.1 g/cm3
Boiling Point	773.6±70.0 °C at 760 mmHg
Molecular Formula	C₂₅H₁₉N₅OS₂
Molecular Weight	469.581
Flash Point	421.7±35.7 °C
Exact Mass	469.103088
LogP	5.18
Appearance	light yellow solid
Vapour Pressure	0.0±2.7 mmHg at 25°C
Index of Refraction	1.816
Storage condition	-20℃

Symbol	GHS06
Signal Word	Danger
Hazard Statements	H301
Precautionary Statements	P301 + P310
RIDADR	UN 2811 6.1 / PGIII