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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.
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
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).
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.
