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.
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
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).
HS Tariff Code: 2934.99.9001
| Biological target: | AR-42 (HDAC-42) is an HDAC inhibitor with IC50 of 30 nM. |
| In vitro activity: | As depicted in Figure 2B, AR-42 effectively restrained the viability of ESCC cells Eca109 and TE-1 in MTT assay with IC50 values of 0.44 μM and 0.28 μM, respectively, which is slightly more potent than that of another approved pan-HDAC inhibitor vorinostat (Corresponding IC50 values for vorinostat are 0.91 μM and 0.78 μM, respectively). As a commonly used clinical chemotherapy drug for ESCC, cisplatin inhibited ESCC cell viability at micromolar concentrations. In addition, the clone formation test was performed to evaluate the anti-ESCC activity after long-term treatment with AR-42. The colonies of both ESCC cells decreased dose-dependently after being treated with AR-42 (Figure 2C). Reference: Drug Des Devel Ther. 2019; 13: 4321–4330. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930838/ |
| In vivo activity: | Oral administrations of AR-42 at 25 and 50 mg/kg potently inhibited tumor growth in a dose-dependent manner with tumor growth inhibition rates of 54.5% and 85.1%, respectively (Fig. 7A). No significant weight loss was observed in AR-42 treated groups compared with vehicle group (data not shown). Additionally, as shown in Fig. 7B, AR-42 at 50 mg/kg evidently restrained TAZ expression in vivo. Meanwhile, the immunohistochemical assays showed that AR-42 could also lead to a significant decrease in Ki67-positive tumor cells (proliferating cells) and substantial increase in TUNEL-positive tumor cells (apoptotic cells) in xenograft model (Fig. (Fig.7B7B and and7C).7C). To sum up, AR-42 could also inhibit the expression of TAZ in vivo, thus exerting its effects of anti-proliferation and pro-apoptosis in SCC9 xenograft. Reference: J Cancer. 2020; 11(2): 364–373. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930442/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 63.0 | 201.69 | |
| Ethanol | 63.0 | 201.69 |
The following data is based on the product molecular weight 312.36 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.
| 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. Zhu Y, Yuan T, Zhang Y, Shi J, Bai L, Duan X, Tong R, Zhong L. AR-42: A Pan-HDAC Inhibitor with Antitumor and Antiangiogenic Activities in Esophageal Squamous Cell Carcinoma. Drug Des Devel Ther. 2019 Dec 19;13:4321-4330. doi: 10.2147/DDDT.S211665. PMID: 31908417; PMCID: PMC6930838. 2. Chen YJ, Wang WH, Wu WY, Hsu CC, Wei LR, Wang SF, Hsu YW, Liaw CC, Tsai WC. Novel histone deacetylase inhibitor AR-42 exhibits antitumor activity in pancreatic cancer cells by affecting multiple biochemical pathways. PLoS One. 2017 Aug 22;12(8):e0183368. doi: 10.1371/journal.pone.0183368. PMID: 28829799; PMCID: PMC5567660. 3. Su L, Wang S, Yuan T, Xie X, Fu X, Ji P, Zhong L, Liu W. Anti-oral Squamous Cell Carcinoma Effects of a Potent TAZ Inhibitor AR-42. J Cancer. 2020 Jan 1;11(2):364-373. doi: 10.7150/jca.32436. PMID: 31897232; PMCID: PMC6930442. 4. Duan S, Gong X, Liu X, Cui W, Chen K, Mao L, Jun S, Zhou R, Sang Y, Huang G. Histone deacetylase inhibitor, AR-42, exerts antitumor effects by inducing apoptosis and cell cycle arrest in Y79 cells. J Cell Physiol. 2019 Dec;234(12):22411-22423. doi: 10.1002/jcp.28806. Epub 2019 May 17. PMID: 31102271. |
| In vitro protocol: | 1. Zhu Y, Yuan T, Zhang Y, Shi J, Bai L, Duan X, Tong R, Zhong L. AR-42: A Pan-HDAC Inhibitor with Antitumor and Antiangiogenic Activities in Esophageal Squamous Cell Carcinoma. Drug Des Devel Ther. 2019 Dec 19;13:4321-4330. doi: 10.2147/DDDT.S211665. PMID: 31908417; PMCID: PMC6930838. 2. Chen YJ, Wang WH, Wu WY, Hsu CC, Wei LR, Wang SF, Hsu YW, Liaw CC, Tsai WC. Novel histone deacetylase inhibitor AR-42 exhibits antitumor activity in pancreatic cancer cells by affecting multiple biochemical pathways. PLoS One. 2017 Aug 22;12(8):e0183368. doi: 10.1371/journal.pone.0183368. PMID: 28829799; PMCID: PMC5567660. |
| In vivo protocol: | 1. Su L, Wang S, Yuan T, Xie X, Fu X, Ji P, Zhong L, Liu W. Anti-oral Squamous Cell Carcinoma Effects of a Potent TAZ Inhibitor AR-42. J Cancer. 2020 Jan 1;11(2):364-373. doi: 10.7150/jca.32436. PMID: 31897232; PMCID: PMC6930442. 2. Duan S, Gong X, Liu X, Cui W, Chen K, Mao L, Jun S, Zhou R, Sang Y, Huang G. Histone deacetylase inhibitor, AR-42, exerts antitumor effects by inducing apoptosis and cell cycle arrest in Y79 cells. J Cell Physiol. 2019 Dec;234(12):22411-22423. doi: 10.1002/jcp.28806. Epub 2019 May 17. PMID: 31102271. |
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.
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).
