Inauhzin
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MedKoo CAT#: 406518

CAS#: 309271-94-1

Description: Inauhzin is a potent SIRT inhibitor, which effectively reactivates p53 by inhibiting SIRT1 activity, promotes p53-dependent apoptosis of human cancer cells without causing apparently genotoxic stress. Moreover, Inauhzin stabilizes p53 by increasing p53 acetylation and preventing MDM2-mediated ubiquitylation of p53 in cells, though not directly in vitro. Remarkably, Inauhzin inhibits cell proliferation, induces senescence and tumour-specific apoptosis, and represses the growth of xenograft tumours derived from p53-harbouring H460 and HCT116 cells without causing apparent toxicity to normal tissues and the tumour-bearing SCID mice.


Chemical Structure

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Inauhzin
CAS# 309271-94-1

Theoretical Analysis

MedKoo Cat#: 406518
Name: Inauhzin
CAS#: 309271-94-1
Chemical Formula: C25H19N5OS2
Exact Mass: 469.10
Molecular Weight: 469.581
Elemental Analysis: C, 63.94; H, 4.08; N, 14.91; O, 3.41; S, 13.66

Price and Availability

Size Price Availability Quantity
100mg USD 950
200mg USD 1650
500mg USD 2650
1g USD 3750
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Synonym: Inauhzin

IUPAC/Chemical Name: 2-((5H-[1,2,4]triazino[5,6-b]indol-3-yl)thio)-1-(10H-phenothiazin-10-yl)butan-1-one

InChi Key: VHUOXERIKQWIJE-UHFFFAOYSA-N

InChi Code: InChI=1S/C25H19N5OS2/c1-2-19(33-25-27-23-22(28-29-25)15-9-3-4-10-16(15)26-23)24(31)30-17-11-5-7-13-20(17)32-21-14-8-6-12-18(21)30/h3-14,19H,2H2,1H3,(H,26,27,29)

SMILES Code: CCC(SC1=NN=C2C(NC3=C2C=CC=C3)=N1)C(N4C5=C(C=CC=C5)SC6=CC=CC=C46)=O

Appearance: white 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:         

Product Data:
Biological target: Inauhzin is a dual SirT1/IMPDH2 inhibitor, and acts as an activator p53, used in the research of cancer.
In vitro activity: As expected, INZ(c) (inauhzin) treatment decreased C23 mRNA level significantly in both Boston and Raji cells (Fig. 2A), indicating INZ(c) indeed suppresses c-Myc transcriptional activity. As shown in Figure 2B, a low concentration (0.63 μM) of INZ(c) dramatically inhibited the proliferation of Raji cells. This result was confirmed by the MTT assay that showed INZ(c) suppresses cell viability of Raji cells too (Fig. 2C). To further validate these results, FACS analysis showed that INZ(c) treatment decreases the number of cells in S phase and arrests cells at G1 phase dose-dependently (Fig. 2D), which is in line with literature showing c-Myc activity is required for cells to enter S phase.25 These results show that INZ(c) inhibits the growth of lymphoma cells. Reference: Cancer Biol Ther. 2015;16(3):412-9. https://pubmed.ncbi.nlm.nih.gov/25692307/
In vivo activity: Additionally, as shown in Figure 6C, a statistically significant difference in tumor volume as compared with the control was observed for the n-INZ-C (inauhzin) treated mice starting from day 6 after treatment. Hence, these results indicate that n-INZ-C more effectively inhibits the growth of xenograft lung tumors than INZ-C alone. Reference: Theranostics. 2021 May 12;11(14):7005-7017. https://pubmed.ncbi.nlm.nih.gov/34093867/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 20.0 42.59
DMF:PBS (pH 7.2) (1:1) 0.3 0.64
DMSO 43.0 91.57

Preparing Stock Solutions

The following data is based on the product molecular weight 469.58 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. Jung JH, Liao JM, Zhang Q, Zeng S, Nguyen D, Hao Q, Zhou X, Cao B, Kim SH, Lu H. Inauhzin(c) inactivates c-Myc independently of p53. Cancer Biol Ther. 2015;16(3):412-9. doi: 10.1080/15384047.2014.1002698. PMID: 25692307; PMCID: PMC4622711. 2. Zhang Q, Zhou X, Wu R, Mosley A, Zeng SX, Xing Z, Lu H. The role of IMP dehydrogenase 2 in Inauhzin-induced ribosomal stress. Elife. 2014 Oct 27;3:e03077. doi: 10.7554/eLife.03077. PMID: 25347121; PMCID: PMC4209374. 3. Bhattarai N, Wang J, Nguyen D, Yang X, Helmers L, Paruch J, Li L, Zhang Y, Meng K, Wang A, Jayawickramarajah J, Wang B, Zeng S, Lu H. Nanoparticle encapsulation of non-genotoxic p53 activator Inauhzin-C for improved therapeutic efficacy. Theranostics. 2021 May 12;11(14):7005-7017. doi: 10.7150/thno.57404. PMID: 34093867; PMCID: PMC8171090. 4. Zhang Q, Zeng SX, Zhang Y, Zhang Y, Ding D, Ye Q, Meroueh SO, Lu H. A small molecule Inauhzin inhibits SIRT1 activity and suppresses tumour growth through activation of p53. EMBO Mol Med. 2012 Apr;4(4):298-312. doi: 10.1002/emmm.201100211. Epub 2012 Feb 13. PMID: 22331558; PMCID: PMC3376857.
In vitro protocol: 1. Jung JH, Liao JM, Zhang Q, Zeng S, Nguyen D, Hao Q, Zhou X, Cao B, Kim SH, Lu H. Inauhzin(c) inactivates c-Myc independently of p53. Cancer Biol Ther. 2015;16(3):412-9. doi: 10.1080/15384047.2014.1002698. PMID: 25692307; PMCID: PMC4622711. 2. Zhang Q, Zhou X, Wu R, Mosley A, Zeng SX, Xing Z, Lu H. The role of IMP dehydrogenase 2 in Inauhzin-induced ribosomal stress. Elife. 2014 Oct 27;3:e03077. doi: 10.7554/eLife.03077. PMID: 25347121; PMCID: PMC4209374.
In vivo protocol: 1. Bhattarai N, Wang J, Nguyen D, Yang X, Helmers L, Paruch J, Li L, Zhang Y, Meng K, Wang A, Jayawickramarajah J, Wang B, Zeng S, Lu H. Nanoparticle encapsulation of non-genotoxic p53 activator Inauhzin-C for improved therapeutic efficacy. Theranostics. 2021 May 12;11(14):7005-7017. doi: 10.7150/thno.57404. PMID: 34093867; PMCID: PMC8171090. 2. Zhang Q, Zeng SX, Zhang Y, Zhang Y, Ding D, Ye Q, Meroueh SO, Lu H. A small molecule Inauhzin inhibits SIRT1 activity and suppresses tumour growth through activation of p53. EMBO Mol Med. 2012 Apr;4(4):298-312. doi: 10.1002/emmm.201100211. Epub 2012 Feb 13. PMID: 22331558; PMCID: PMC3376857.

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1: Zhang Y, Zhang Q, Zeng SX, Hao Q, Lu H. Inauhzin sensitizes p53-dependent cytotoxicity and tumor suppression of chemotherapeutic agents. Neoplasia. 2013 May;15(5):523-34. PubMed PMID: 23633924; PubMed Central PMCID: PMC3638355.

2: Liao JM, Zeng SX, Zhou X, Lu H. Global effect of inauhzin on human p53-responsive transcriptome. PLoS One. 2012;7(12):e52172. doi: 10.1371/journal.pone.0052172. Epub 2012 Dec 21. PubMed PMID: 23284922; PubMed Central PMCID: PMC3528779.

3: Zhang Q, Ding D, Zeng SX, Ye QZ, Lu H. Structure and activity analysis of Inauhzin analogs as novel antitumor compounds that induce p53 and inhibit cell growth. PLoS One. 2012;7(10):e46294. doi: 10.1371/journal.pone.0046294. Epub 2012 Oct 24. PubMed PMID: 23115626; PubMed Central PMCID: PMC3480348.

4: Zhang Y, Zhang Q, Zeng SX, Zhang Y, Mayo LD, Lu H. Inauhzin and Nutlin3 synergistically activate p53 and suppress tumor growth. Cancer Biol Ther. 2012 Aug;13(10):915-24. doi: 10.4161/cbt.20844. Epub 2012 Aug 1. PubMed PMID: 22785205; PubMed Central PMCID: PMC3414413.

5: Zhang Q, Zeng SX, Zhang Y, Zhang Y, Ding D, Ye Q, Meroueh SO, Lu H. A small molecule Inauhzin inhibits SIRT1 activity and suppresses tumour growth through activation of p53. EMBO Mol Med. 2012 Apr;4(4):298-312. doi: 10.1002/emmm.201100211. Epub 2012 Feb 13. PubMed PMID: 22331558; PubMed Central PMCID: PMC3376857.