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MedKoo Cat#: 200272 | Name: OSU-03012
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Description:

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

OSU03012; also known as AR12, is an orally available, targeted anti-cancer agent that has been shown in pre-clinical studies to inhibit PDK-1, a protein in the PI3K/Akt pathway that is involved in the growth and proliferation of cells, including cancer cells. AR-12 may also cause cell death through the induction of stress in the endoplasmic reticulum. We are currently conducting a multi-centered Phase I clinical study of AR-12 in adult patients with advanced or recurrent solid tumors or lymphoma.

Chemical Structure

OSU-03012
OSU-03012
CAS#742112-33-0 (free base)

Theoretical Analysis

MedKoo Cat#: 200272

Name: OSU-03012

CAS#: 742112-33-0 (free base)

Chemical Formula: C26H19F3N4O

Exact Mass: 460.1511

Molecular Weight: 460.45

Elemental Analysis: C, 67.82; H, 4.16; F, 12.38; N, 12.17; O, 3.47

Price and Availability

Size Price Availability Quantity
10mg USD 110.00 Ready to ship
25mg USD 220.00 Ready to ship
50mg USD 350.00 Ready to ship
100mg USD 600.00 Ready to ship
200mg USD 1,050.00 Ready to ship
500mg USD 2,250.00 Ready to ship
1g USD 3,450.00 Ready to ship
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Related CAS #
742112-33-0 (free base) 1471979-81-3 (HCl)
Synonym
AR12; AR-12; AR 12; OSU03012; OSU-03012; OSU 03012.
IUPAC/Chemical Name
2-amino-N-{4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl} acetamide
InChi Key
YULUCECVQOCQFQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C26H19F3N4O/c27-26(28,29)24-14-23(33(32-24)20-10-8-19(9-11-20)31-25(34)15-30)18-7-12-22-17(13-18)6-5-16-3-1-2-4-21(16)22/h1-14H,15,30H2,(H,31,34)
SMILES Code
O=C(NC1=CC=C(N2N=C(C(F)(F)F)C=C2C3=CC=C4C5=CC=CC=C5C=CC4=C3)C=C1)CN
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 soluble in water.
Shelf Life
>5 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
Related: 742112-33-0(AR-12) 1471979-81-3 (AR-12 Hydrochloride) AR-12 (formerly known as OSU-03012) is a potentially first-in-class, orally available, targeted anti-cancer agent that inhibits PDK-1, a protein in the PI3K/Akt pathway, and also causes cell death through the induction of endoplasmic reticulum (ER) stress. Arno is currently enrolling patients with advanced or recurrent solid tumors or lymphoma in a Phase I clinical study. Preclinical data have demonstrated that AR-12 has activity in a wide range of tumor types and sas both a single agent and in combination with several widely used anti-cancer agents including Avastin®, Herceptin®, Gleevec®, Tarceva®, Sorafinib®, Nexavar®, and tamoxifen.   OSU-03012 is a derivative of celecoxib with anticancer activity. The mechanism of action is presumably 3-phosphoinositide-dependent kinase 1 (PDK1) inhibition.  OSU-03012 inhibited cell growth of Huh7, Hep3B, and HepG2 cells with IC(50) below 1 mumol/L. In Huh7 cells, OSU-03012 did not suppress PDK1 or AKT activity. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and flow cytometry analysis indicated that OSU-03012 did not induce cellular apoptosis. Instead, morphologic studies by light and electron microscopy, as well as special biological staining with monodansylcadaverine, acridine orange, and microtubule-associated protein 1 light chain 3, revealed OSU-03012-induced autophagy of Huh7 cells. This OSU-03012-induced autophagy was inhibited by 3-methyladenine. Moreover, reactive oxygen species (ROS) accumulation was detected after OSU-03012 treatment. Blocking ROS accumulation with ROS scavengers inhibited autophagy formation, indicating that ROS accumulation and subsequent autophagy formation might be a major mechanism of action of OSU-03012. Daily oral treatment of BALB/c nude mice with OSU-03012 suppressed the growth of Huh7 tumor xenografts. Electron microscopic observation indicated that OSU-03012 induced autophagy in vivo. Together, our results show that OSU-03012 induces autophagic cell death but not apoptosis in HCC and that the autophagy-inducing activity is at least partially related to ROS accumulation.( source: Cancer Res. 2008 Nov 15;68(22):9348-57., or http://www.ncbi.nlm.nih.gov/pubmed/19010909).        
Biological target:
OSU-03012 (AR-12) is an inhibitor of recombinant PDK-1(phosphoinositide-dependent kinase 1) with IC50 of 5 μM.
In vitro activity:
Vero cells were treated with AR12 (1 μM; 2 μM) and then infected with SARS-CoV-2 at 0.01 and 0.001 multiplicities of infection (MOI). Twenty-four and forty-eight hours after infection, cells were fixed in place and permeabilized, and stained for expression of the SARS-CoV-2 spike protein, total GRP78 and total ERK2 as a loading control. In a dose-dependent fashion, AR12 suppressed the production of virus spike protein (Fig. 2 A and B). Cells were then infected and treated with AR12 (2 μM) 3 h, 6 h and 12 h after infection, with cells being fixed and stained 24 h after infection. Treatment of infected cells with AR12 significantly reduced the amount of spike protein produced in the infected cells as well as the amount of GRP78 in the cells (Fig. 2C and D). Reference: Biochem Pharmacol. 2020 Dec; 182: 114227. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502229/
In vivo activity:
To study the effects of OSU-03012 on tumor progression in vivo, this study treated the Ishikawa xenograft with OSU-03012. First of all, compared with the control group, the tumor volume of mice in the OSU-03012 treatment group was significantly reduced (Figure 6A and B).The results showed that the mass and volume of the tumor were significantly reduced with OSU-03012 treatment (0.222 ± 0.07235g, 339.6 ± 103.2 mm3, n=5) relative to the vehicle controls (0.624 ± 0.02694 g, 1170 ± 84.51 mm3, n=5, Figure 6C and E); meanwhile, the body weights of the mice remained consistent throughout the duration of the experiment, exhibiting no serious toxicity at specified dose regimens (Figure 6D). These results demonstrate that oral administration of OSU-03012 can prevent EC progression. Reference: Drug Des Devel Ther. 2021; 15: 1797–1810. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096345/
Solvent mg/mL mM
Solubility
DMSO 30.0 65.20
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 460.45 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. Rayner JO, Roberts RA, Kim J, Poklepovic A, Roberts JL, Booth L, Dent P. AR12 (OSU-03012) suppresses GRP78 expression and inhibits SARS-CoV-2 replication. Biochem Pharmacol. 2020 Dec;182:114227. doi: 10.1016/j.bcp.2020.114227. Epub 2020 Sep 20. PMID: 32966814; PMCID: PMC7502229. 2. Zhang S, Zou Y, Guo Q, Chen J, Xu L, Wan X, Zhang Z, Li B, Chu H. AR-12 Exhibits Direct and Host-Targeted Antibacterial Activity toward Mycobacterium abscessus. Antimicrob Agents Chemother. 2020 Jul 22;64(8):e00236-20. doi: 10.1128/AAC.00236-20. PMID: 32482678; PMCID: PMC7526805. 3. Ding L, Ren C, Yang L, Wu Z, Li F, Jiang D, Zhu Y, Lu J. OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo. Drug Des Devel Ther. 2021 Apr 30;15:1797-1810. doi: 10.2147/DDDT.S304128. PMID: 33958857; PMCID: PMC8096345. 4. Chan JF, Zhu Z, Chu H, Yuan S, Chik KK, Chan CC, Poon VK, Yip CC, Zhang X, Tsang JO, Zou Z, Tee KM, Shuai H, Lu G, Yuen KY. The celecoxib derivative kinase inhibitor AR-12 (OSU-03012) inhibits Zika virus via down-regulation of the PI3K/Akt pathway and protects Zika virus-infected A129 mice: A host-targeting treatment strategy. Antiviral Res. 2018 Dec;160:38-47. doi: 10.1016/j.antiviral.2018.10.007. Epub 2018 Oct 13. PMID: 30326204; PMCID: PMC7113887.
In vitro protocol:
1. Rayner JO, Roberts RA, Kim J, Poklepovic A, Roberts JL, Booth L, Dent P. AR12 (OSU-03012) suppresses GRP78 expression and inhibits SARS-CoV-2 replication. Biochem Pharmacol. 2020 Dec;182:114227. doi: 10.1016/j.bcp.2020.114227. Epub 2020 Sep 20. PMID: 32966814; PMCID: PMC7502229. 2. Zhang S, Zou Y, Guo Q, Chen J, Xu L, Wan X, Zhang Z, Li B, Chu H. AR-12 Exhibits Direct and Host-Targeted Antibacterial Activity toward Mycobacterium abscessus. Antimicrob Agents Chemother. 2020 Jul 22;64(8):e00236-20. doi: 10.1128/AAC.00236-20. PMID: 32482678; PMCID: PMC7526805.
In vivo protocol:
1. Ding L, Ren C, Yang L, Wu Z, Li F, Jiang D, Zhu Y, Lu J. OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo. Drug Des Devel Ther. 2021 Apr 30;15:1797-1810. doi: 10.2147/DDDT.S304128. PMID: 33958857; PMCID: PMC8096345. 2. Chan JF, Zhu Z, Chu H, Yuan S, Chik KK, Chan CC, Poon VK, Yip CC, Zhang X, Tsang JO, Zou Z, Tee KM, Shuai H, Lu G, Yuen KY. The celecoxib derivative kinase inhibitor AR-12 (OSU-03012) inhibits Zika virus via down-regulation of the PI3K/Akt pathway and protects Zika virus-infected A129 mice: A host-targeting treatment strategy. Antiviral Res. 2018 Dec;160:38-47. doi: 10.1016/j.antiviral.2018.10.007. Epub 2018 Oct 13. PMID: 30326204; PMCID: PMC7113887.
1: Abdulrahman A, Mohammad Azhar K, Asif Hussain A, Ali Abdullah A, Marui IS, Mohammed Hadi G, Hanan Mamdouh A, Qamre A. Molecular docking analysis of MCL-1 inhibitors for breast cancer management. Bioinformation. 2023 Jun 30;19(6):707-712. doi: 10.6026/97320630019707. PMID: 37885779; PMCID: PMC10598365. 2: Li ZF, Zhang R, Zhao GR, Kuang Y. Electroacupuncture inhibits PDK1/Akt/HCN4 pathway to improve neurogenic urinary retention in rats. Zhen Ci Yan Jiu. 2023 Oct 25;48(10):969-976. English, Chinese. doi: 10.13702/j.1000-0607.20221084. PMID: 37879946. 3: Lai X, Fu G, Du H, Xie Z, Lin S, Li Q, Lin K. Identification of a cancer- associated fibroblast classifier for predicting prognosis and therapeutic response in lung squamous cell carcinoma. Medicine (Baltimore). 2023 Sep 22;102(38):e35005. doi: 10.1097/MD.0000000000035005. PMID: 37746966; PMCID: PMC10519496. 4: Ma X, Sun L. Construction and Validation of Protein Expression-related Prognostic Models in Clear Cell Renal Cell Carcinoma. J Cancer. 2023 Mar 27;14(5):793-808. doi: 10.7150/jca.81915. PMID: 37056387; PMCID: PMC10088890. 5: Li F, Niu Y, Zhao W, Yan C, Qi Y. Construction and validation of a prognostic model for lung adenocarcinoma based on endoplasmic reticulum stress-related genes. Sci Rep. 2022 Nov 18;12(1):19857. doi: 10.1038/s41598-022-23852-z. PMID: 36400857; PMCID: PMC9674626. 6: Lee D, Lee Y, Hye Shin S, Min Choi S, Hyeon Lee S, Jeong S, Jang S, Kee JM. A simple protein histidine kinase activity assay for high-throughput inhibitor screening. Bioorg Chem. 2023 Jan;130:106232. doi: 10.1016/j.bioorg.2022.106232. Epub 2022 Nov 2. PMID: 36371819. 7: Mattos DR, Weinman MA, Wan X, Goodall CP, Serrill JD, McPhail KL, Milovancev M, Bracha S, Ishmael JE. Canine osteosarcoma cells exhibit basal accumulation of multiple chaperone proteins and are sensitive to small molecule inhibitors of GRP78 and heat shock protein function. Cell Stress Chaperones. 2022 May;27(3):223-239. doi: 10.1007/s12192-022-01263-3. Epub 2022 Mar 4. PMID: 35244890; PMCID: PMC9106791. 8: Tsao N, Chang YC, Hsieh SY, Li TC, Chiu CC, Yu HH, Hsu TC, Kuo CF. AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A Streptococcus. Int J Mol Sci. 2021 Oct 27;22(21):11617. doi: 10.3390/ijms222111617. PMID: 34769046; PMCID: PMC8583967. 9: Sobolewski C, Legrand N. Celecoxib Analogues for Cancer Treatment: An Update on OSU-03012 and 2,5-Dimethyl-Celecoxib. Biomolecules. 2021 Jul 16;11(7):1049. doi: 10.3390/biom11071049. PMID: 34356673; PMCID: PMC8302000. 10: Zahid MSH, Varma DM, Johnson MM, Landavazo A, Bachelder EM, Blough BE, Ainslie KM. Overcoming reduced antibiotic susceptibility in intracellular Salmonella enterica serovar Typhimurium using AR-12. FEMS Microbiol Lett. 2021 Jun 16;368(11):fnab062. doi: 10.1093/femsle/fnab062. PMID: 34089315; PMCID: PMC8433491. 11: Ding L, Ren C, Yang L, Wu Z, Li F, Jiang D, Zhu Y, Lu J. OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo. Drug Des Devel Ther. 2021 Apr 30;15:1797-1810. doi: 10.2147/DDDT.S304128. PMID: 33958857; PMCID: PMC8096345. 12: Baloni P, Dinalankara W, Earls JC, Knijnenburg TA, Geman D, Marchionni L, Price ND. Identifying Personalized Metabolic Signatures in Breast Cancer. Metabolites. 2020 Dec 30;11(1):20. doi: 10.3390/metabo11010020. PMID: 33396819; PMCID: PMC7823382. 13: Rayner JO, Roberts RA, Kim J, Poklepovic A, Roberts JL, Booth L, Dent P. AR12 (OSU-03012) suppresses GRP78 expression and inhibits SARS-CoV-2 replication. Biochem Pharmacol. 2020 Dec;182:114227. doi: 10.1016/j.bcp.2020.114227. Epub 2020 Sep 20. PMID: 32966814; PMCID: PMC7502229. 14: Zhang S, Zou Y, Guo Q, Chen J, Xu L, Wan X, Zhang Z, Li B, Chu H. AR-12 Exhibits Direct and Host-Targeted Antibacterial Activity toward Mycobacterium abscessus. Antimicrob Agents Chemother. 2020 Jul 22;64(8):e00236-20. doi: 10.1128/AAC.00236-20. PMID: 32482678; PMCID: PMC7526805. 15: Ma X, Jin L, Lei X, Tong J, Wang R. MicroRNA‑363‑3p inhibits cell proliferation and induces apoptosis in retinoblastoma cells via the Akt/mTOR signaling pathway by targeting PIK3CA. Oncol Rep. 2020 May;43(5):1365-1374. doi: 10.3892/or.2020.7544. Epub 2020 Mar 12. PMID: 32323827; PMCID: PMC7107813. 16: Park JG, Ávila-Pérez G, Nogales A, Blanco-Lobo P, de la Torre JC, Martínez- Sobrido L. Identification and Characterization of Novel Compounds with Broad- Spectrum Antiviral Activity against Influenza A and B Viruses. J Virol. 2020 Mar 17;94(7):e02149-19. doi: 10.1128/JVI.02149-19. PMID: 31941776; PMCID: PMC7081893. 17: Abt ER, Rosser EW, Durst MA, Lok V, Poddar S, Le TM, Cho A, Kim W, Wei L, Song J, Capri JR, Xu S, Wu N, Slavik R, Jung ME, Damoiseaux R, Czernin J, Donahue TR, Lavie A, Radu CG. Metabolic Modifier Screen Reveals Secondary Targets of Protein Kinase Inhibitors within Nucleotide Metabolism. Cell Chem Biol. 2020 Feb 20;27(2):197-205.e6. doi: 10.1016/j.chembiol.2019.10.012. Epub 2019 Nov 13. PMID: 31734178; PMCID: PMC7035983. 18: Zahid MSH, Johnson MM, Tokarski RJ 2nd, Satoskar AR, Fuchs JR, Bachelder EM, Ainslie KM. Evaluation of synergy between host and pathogen-directed therapies against intracellular Leishmania donovani. Int J Parasitol Drugs Drug Resist. 2019 Aug;10:125-132. doi: 10.1016/j.ijpddr.2019.08.004. Epub 2019 Aug 21. PMID: 31493763; PMCID: PMC6731340. 19: Booth L, Roberts JL, Cruickshanks N, Grant S, Poklepovic A, Dent P. Editor's Note: Regulation of OSU-03012 Toxicity by ER Stress Proteins and ER Stress- Inducing Drugs. Mol Cancer Ther. 2019 Sep;18(9):1669. doi: 10.1158/1535-7163.MCT-19-0666. Erratum for: Mol Cancer Ther. 2014 Oct;13(10):2384-98. doi: 10.1158/1535-7163.MCT-14-0172. PMID: 31481480. 20: Barker WT, Nemeth AM, Brackett SM, Basak AK, Chandler CE, Jania LA, Zuercher WJ, Melander RJ, Koller BH, Ernst RK, Melander C. Repurposing Eukaryotic Kinase Inhibitors as Colistin Adjuvants in Gram-Negative Bacteria. ACS Infect Dis. 2019 Oct 11;5(10):1764-1771. doi: 10.1021/acsinfecdis.9b00212. Epub 2019 Sep 4. PMID: 31434474; PMCID: PMC6944324.

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