AR-42

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

MedKoo CAT#: 200275

CAS#: 935881-37-1

Description: AR-42, also known as S)-HDAC-42; AR-42; NSC-736012; OSU-42; OSU-HDAC-42; OSUHDAC-42, is a broad-spectrum deacetylase inhibitor of both histone and non-histone proteins, which has demonstrated greater potency and activity in solid tumors and hematological malignancies when compared in preclinical studies to vorinostat (also known as "SAHA" or Zolinza®), the first of two marketed compound in the class. AR-42 may possess additional histone-independent mechanisms, which may contribute to its superior profile in vitro and in vivo.


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10mg
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1g
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25mg
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200mg
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2g
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50mg
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500mg
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5g
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AR-42, purity > 98%, is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 200275
Name: AR-42
CAS#: 935881-37-1
Chemical Formula: C18H20N2O3
Exact Mass: 312.14739
Molecular Weight: 312.36
Elemental Analysis: C, 69.21; H, 6.45; N, 8.97; O, 15.37


Synonym: AR42; AR 42; AR-42; (S)-HDAC-42; AR-42; NSC-736012; OSU-42; OSU-HDAC-42; OSUHDAC-42

IUPAC/Chemical Name: (S)-N-hydroxy-4-(3-methyl-2-phenylbutanamido)benzamide

InChi Key: LAMIXXKAWNLXOC-INIZCTEOSA-N

InChi Code: InChI=1S/C18H20N2O3/c1-12(2)16(13-6-4-3-5-7-13)18(22)19-15-10-8-14(9-11-15)17(21)20-23/h3-12,16,23H,1-2H3,(H,19,22)(H,20,21)/t16-/m0/s1

SMILES Code: O=C(NO)C1=CC=C(NC([C@H](C2=CC=CC=C2)C(C)C)=O)C=C1


Technical Data

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, 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).

Harmonized System Code:
293490


Additional Information

 AR-42 is a novel class I and II DAC inhibitor that has shown pre-clinical activity in a variety of solid tumor in vitro and in vivo models. (S)-HDAC-42 is a potent orally bioavailable inhibitor of HDAC, as well as targets regulating multiple aspects of cancer cell survival, which might have clinical value in prostate cancer chemotherapy and warrants further investigation in this regard. (source: Clin Cancer Res. 2006 Sep 1;12(17):5199-206.).
 AR-42 is a novel class I and II DAC inhibitor that has shown pre-clinical activity in a variety of solid tumor in vitro and in vivo models. (S)-HDAC-42 is a potent orally bioavailable inhibitor of HDAC, as well as targets regulating multiple aspects of cancer cell survival, which might have clinical value in prostate cancer chemotherapy and warrants further investigation in this regard. (source: Clin Cancer Res. 2006 Sep 1;12(17):5199-206.).
 
Arno is also developing AR-42 (formerly known as "HDAC-42"), an orally available, broad spectrum inhibitor of both histone and non-histone deacetylation proteins ("pan-DAC"), which may both be important in cancer progression. Histone deacetylase ("HDAC") inhibitors are a growing class of compounds that target histone deactylase, a molecule involved in determining which genes are expressed in a particular cell. This class has two approved agents, vorinostat ("SAHA," or Zolinza® by Merck) and romidepsin (Istodax®, Celgene) . In preclinical studies, AR-42 has shown increased potency compared to SAHA, activity against a broad spectrum of deacetylation targets, and unique mechanisms for killing tumor-forming cancer stem cells (Hassane, et al). Recently published preclinical research done in the lab of of John Byrd, MD at the Ohio State University demonstrated the in vitro and in vivo efficacy of AR-42 against B-cell malignancites at tolerable doses, and these results also suggested that AR-42 has greater efficacy in vitro as well as in vivo compared to vorinostat (Lucas, et al). This combination of activity and potency may provide for a toxicity and efficacy profile that differentiates AR-42 from other HDAC inhibitors in this emerging class of compounds.
Arno is also developing AR-42 (formerly known as "HDAC-42"), an orally available, broad spectrum inhibitor of both histone and non-histone deacetylation proteins ("pan-DAC"), which may both be important in cancer progression. Histone deacetylase ("HDAC") inhibitors are a growing class of compounds that target histone deactylase, a molecule involved in determining which genes are expressed in a particular cell. This class has two approved agents, vorinostat ("SAHA," or Zolinza® by Merck) and romidepsin (Istodax®, Celgene) . In preclinical studies, AR-42 has shown increased potency compared to SAHA, activity against a broad spectrum of deacetylation targets, and unique mechanisms for killing tumor-forming cancer stem cells (Hassane, et al). Recently published preclinical research done in the lab of of John Byrd, MD at the Ohio State University demonstrated the in vitro and in vivo efficacy of AR-42 against B-cell malignancites at tolerable doses, and these results also suggested that AR-42 has greater efficacy in vitro as well as in vivo compared to vorinostat (Lucas, et al). This combination of activity and potency may provide for a toxicity and efficacy profile that differentiates AR-42 from other HDAC inhibitors in this emerging class of compounds.
Arno is currently enrolling an investigator-initiated Phase I/IIa study with AR-42 in collaboration with The Ohio State University in adult patients with relapsed or refractory multiple myeloma (MM), chronic lymphocytic leukemia (CLL) or lymphoma. (source: Arno Therapeutics, Inc., webpages: http://www.arnothera.com/ar42.html).
Arno is currently enrolling an investigator-initiated Phase I/IIa study with AR-42 in collaboration with The Ohio State University in adult patients with relapsed or refractory multiple myeloma (MM), chronic lymphocytic leukemia (CLL) or lymphoma. (source: Arno Therapeutics, Inc., webpages: http://www.arnothera.com/ar42.html).
 
 
 


References

1: Zhang S, Suvannasankha A, Crean CD, White VL, Chen CS, Farag SS. The novel histone deacetylase inhibitor, AR-42, inhibits gp130/Stat3 pathway and induces apoptosis and cell cycle arrest in multiple myeloma cells. Int J Cancer. 2011 Jul 1;129(1):204-13. doi: 10.1002/ijc.25660. Epub 2010 Dec 1. PubMed PMID: 20824695.

2: Lucas DM, Alinari L, West DA, Davis ME, Edwards RB, Johnson AJ, Blum KA, Hofmeister CC, Freitas MA, Parthun MR, Wang D, Lehman A, Zhang X, Jarjoura D, Kulp SK, Croce CM, Grever MR, Chen CS, Baiocchi RA, Byrd JC. The novel deacetylase inhibitor AR-42 demonstrates pre-clinical activity in B-cell malignancies in vitro and in vivo. PLoS One. 2010 Jun 3;5(6):e10941. PubMed PMID: 20532179; PubMed Central PMCID: PMC2880605.

3: Lin TY, Fenger J, Murahari S, Bear MD, Kulp SK, Wang D, Chen CS, Kisseberth WC, London CA. AR-42, a novel HDAC inhibitor, exhibits biologic activity against malignant mast cell lines via down-regulation of constitutively activated Kit. Blood. 2010 May 27;115(21):4217-25. Epub 2010 Mar 16. PubMed PMID: 20233974.

4: Stoenner RW, Schaeffer OA, Katcoff S. Half-Lives of Argon-37, Argon-39, and Argon-42. Science. 1965 Jun 4;148(3675):1325-8. PubMed PMID: 17791262.