Publications
ON 123300
PUBLICATIONS:
PerumalD, KuoPY, LeshenkoV, et al. (2016). Dual Targeting of CDK4 and ARK5 Using a Novel Kinase Inhibitor ON123300 Exerts Potent Anticancer Activity against Multiple Myeloma. Cancer Research, 76:5, 1225-1236, March
DivakarSK, ReddyMV, CosenzaSC, et al. (2016). Dual inhibition of CDK4/Rb and PI3K/AKT/mTOR pathways by ON123300 induces synthetic lethality in mantle cell lymphomas. Leukemia, 30, 86-93, e-pub August 2015
ReddyMV, AkulaB, CosenzaSC, et al. (2014). Discovery of 8-cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) as a potent inhibitor of cyclin-dependent kinase 4 (CDK4) and AMPK-related kinase 5 (ARK5). Journal of Medicinal Chemistry 57:3, 578-599
LvH, ZhangX, SharmaJ, et al. (2013). Integrated Pharmacokinetic-Driven Approach to Screen Candidate Anticancer Drugs for Brain Tumor Chemotherapy. The AAPS Journal 15:1, 250-257
ABSTRACTS PRESENTED AT SCIENTIFIC CONFERENCES:
RenC, MudunuraJ, TaftD, ManiarM, et al. (2018). Effect of Gender on the Rodent Pharmacokinetics of ON 123300, A Dual Inhibitor of ARK5 and CDK4/6, for the Treatment of Cancer. 2018 AACR Annual Meeting poster, Abstract #4906
PatelS, PancholiP, VisalT, et al. (2017). ON 123300, an orally administered novel CDK4/6 + ARK5 inhibitor, exhibits potent antitumor activity in vivo: comparative studies with Palbociclib. 2017 AACR Annual Meeting poster, Abstract #2172
DivakarSK, ReddyMV, CosenzaSC, et al. (2016). Dual targeting of ARK5 and CDK4 pathways with ON123300 as a therapeutic strategy for colorectal carcinoma. 2016 AACR Annual Meeting poster, Abstract # 3029
HoffmanB, ReddyMV, DivakarSK, et al. (2015). Single-agent activity and favorable pharmaceutical properties of orally bioavailable next-generation CDK4/6 inhibitor, ON 123300. 2015 AACR-NCI-EORTC International Conference poster, Abstract #LB-A21
Rigosertib
Clinical:
Bowles DW, Diamond JR, Lam ET, Weekes CD, Astling DP, Anderson RT, Leong S, Gore L, Varella-Garcia M, Vogler BW, Keysar SB, Freas E, Aisner DL, Ren C, Tan AC, Wilhelm F, Maniar M, Eckhardt SG, Messersmith WA, Jimeno A (2014) Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies. Clin Cancer Res 20: 1656-65
Ohnuma T, Lehrer D, Ren C, Cho SY, Maniar M, Silverman L, Sung M, Gretz HF 3rd, Benisovich V, Navada S, Akahoho E, Wilck E, Taft DR, Roboz J, Wilhelm F, Holland JF (2013) Phase 1 study of intravenous rigosertib (ON 01910.Na), a novel benzyl styryl sulfone structure producing G2/M arrest and apoptosis, in adult patients with advanced cancer. American Journal of Cancer Research 3: 323-338
Roschewski M, Farooqui M, Aue G, Wilhelm F, Wiestner A (2013) Phase I study of ON 01910.Na (Rigosertib), a multikinase PI3K inhibitor in relapsed/refractory B-cell malignancies. Leukemia: ePub 3Mar2013
Ma WW, Messersmith WA, Dy GK, Weekes CD, Whitworth A, Ren C, Maniar M, Wilhelm F, Eckhardt SG, Adjei AA, Jimeno A (2012) Phase I Study of Rigosertib, an Inhibitor of the Phosphatidylinositol 3-Kinase and Polo-like Kinase 1 Pathways, Combined with Gemcitabine in Patients with Solid Tumors and Pancreatic Cancer. Clinical Cancer Research18: 2048-2055
Jimeno A, Li J, Messersmith WA, Laheru D, Rudek MA, Maniar M, Hidalgo M, Baker SD, Donehower RC (2008) Phase I study of ON 01910.Na, a novel modulator of the Polo-like kinase 1 pathway, in adult patients with solid tumors. J Clin Oncol 26: 5504-5510
Reviews and Editorials:
Flemming, A. (2016) RAS mimetic revealed. Nature Reviews Drug Discovery published online June 1, 2016
Bouchie A (2011) Rigosertib's arresting story. BioCentury 18July2011: A6
Kumar CC (2011) Genetic Abnormalities and Challenges in the Treatment of Acute Myeloid Leukemia. Genes & Cancer 2: 95-107
Taft DR, Dave R, Gillum AM, Maniar M (2011) ON 01910.Na. Drugs of the Future 36: 433-440
Nonclinical:
Athuluri-Divakar SK, Vasquez-Del Carpio R, Dutta K, Baker SJ, Cosenza SC, Basu I, Gupta YK, Reddy MV, Ueno L, Hart JR, Vogt PK, Mulholland D, Guha C, Aggarwal AK and Reddy EP (2016) A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling. Cell 165(3): 643-655
Agoni L, Basu I, Gupta S, Alfieri A, Gambino A, Goldberg GL, Reddy EP, Guha C (2014) Rigosertib is a more effective radiosensitizer than cisplatin in concurrent chemoradiation treatment of cervical carcinoma, in vitro and in vivo. Int J Radiat Oncol Biol Phys:ePub 18Feb2014
Pallela VR, Mallireddigari MR, Cosenza SC, Akula B, Subbaiah DR, Reddy EP, Reddy MV (2013) Hydrothiolation of benzyl mercaptan to arylacetylene: application to the synthesis of (E) and (Z)-isomers of ON 01910.Na (Rigosertib(R)), a phase III clinical stage anti-cancer agent. Organic & Biomolecular Chemistry 11: 1964-1977
Chapman CM, Sun X, Roschewski M, Aue G, Farooqui M, Stennett L, Gibellini F, Arthur D, Perez-Galan P, Wiestner A (2012) ON 01910.Na Is Selectively Cytotoxic for Chronic Lymphocytic Leukemia Cells through a Dual Mechanism of Action Involving PI3K/AKT Inhibition and Induction of Oxidative Stress. Clinical Cancer Research 18: 1979-1991
Nuthalapati S, Zhou Q, Guo P, Lv H, Cosenza S, Reddy MV, Reddy EP, Gallo JM (2012) Preclinical pharmacokinetic and pharmacodynamic evaluation of novel anticancer agents, ON01910.Na (Rigosertib, Estybon) and ON013105, for brain tumor chemotherapy. Pharm Res 29: 2499-2511
Lu M, Merali S, Gordon R, Jiang J-D, Li Y, Mandeli J, Duan X, Fallon J, Holland JF (2011) Prevention of Doxorubicin Cardiopathic Changes by a Benzyl Styryl Sulfone in Mice. Genes & Cancer 2: 985-992
Nuthalapati S, Guo P, Zhou Q, Reddy MVR, Reddy EP, Gallo JM (2011) Application of a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to the pharmacokinetics of ON01910 in brain tumor-bearing mice. Journal of Pharmaceutical and Biomedical Analysis 56: 1117-1120
Oussenko IA, Holland JF, Reddy EP, Ohnuma T (2011) Effect of ON 01910.Na, an anticancer mitotic inhibitor, on cell-cycle progression correlates with RanGAP1 hyperphosphorylation. Cancer Res 71: 4968-4976
Reddy MVR, Venkatapuram P, Mallireddigari MR, Pallela VR, Cosenza SC, Robell KA, Akula B, Hoffman BS, Reddy EP (2011) Discovery of a Clinical Stage Multi-Kinase Inhibitor Sodium (E)-2-{2-Methoxy-5-[(2',4',6'-trimethoxystyrylsulfonyl)methyl] phenylamino} acetate (ON 01910.Na): Synthesis, Structure-Activity Relationship, and Biological Activity. Journal of Medicinal Chemistry 54: 6254-6276
Cho SY, Ohnuma T, Silverman LR, Holland JF, Roboz J (2010) Discontinuous Drug Binding to Proteins: Binding of an Antineoplastic Benzyl Styryl Sulfone to Albumin and Enzymes in Vitro and in Phase I Clinical Trials. Drug Metab Dispos 38: 1480-1485
Jimeno A, Rubio-Viqueira B, Rajeshkumar NV, Chan A, Solomon A, Hidalgo M (2010) A fine-needle aspirate-based vulnerability assay identifies polo-like kinase 1 as a mediator of gemcitabine resistance in pancreatic cancer. Mol Cancer Ther 9: 311-318
Chun AW, Cosenza SC, Taft DR, Maniar M (2009) Preclinical pharmacokinetics and in vitro activity of ON 01910.Na, a novel anti-cancer agent. Cancer Chemother Pharmacol 65: 177-186
Prasad A, Park IW, Allen H, Zhang X, Reddy MVR, Boominathan R, Reddy EP, Groopman JE (2009) Styryl sulfonyl compounds inhibit translation of cyclin D1 in mantle cell lymphoma cells. Oncogene 28: 1518-1528
Briciclib
Nonclinical:
Nuthalapati S, Zhou Q, Guo P, Lv H, Cosenza S, Reddy MV, Reddy EP, Gallo JM (2012) Preclinical pharmacokinetic and pharmacodynamic evaluation of novel anticancer agents, ON01910.Na (Rigosertib, Estybon) and ON013105, for brain tumor chemotherapy. Pharm Res 29(9): 2499-2511
Prasad A, Shrivatsava A, Papadopoulos E, Kuzontkoski PM, Reddy MVR, Gillum AM, Kumar R, Reddy EP, Groopman JE (2012) Combined administration of rituximab and ON 013105 induces apoptosis in mantle cell lymphoma cells and reduces tumor burden in a mouse model of mantle cell lymphoma. Clin Cancer Res: ePub 1Nov2012
Reddy MV, Mallireddigari MR, Cosenza SC, Pallela VR, Iqbal NM, Robell KA, Kang AD, Reddy EP (2008) Design, synthesis, and biological evaluation of (E)- styrylbenzylsulfones as novel anticancer agents. J Med Chem 51(1): 86-100
Park IW, Reddy MV, Reddy EP, Groopman JE (2007) Evaluation of novel cell cycle inhibitors in mantle cell lymphoma. Oncogene 26(38): 5635-5642
Recilisib
Nonclinical:
Kang AD, Cosenza SC, Bonagura M, Maniar M, Reddy MVR, Ren Q, Rodeck U, Reddy EP (2013) ON 01210.Na (Ex-RAD®) mitigates radiation damage through activation of the AKT pathway. PLOS 8: e58355
Ghosh SP, Kulkarni S, Perkins MW, Hieber K, Pessu RL, Gambles K, Maniar M, Kao TC, Seed TM, Kumar KS (2012) Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD® in mice. Journal of Radiation Research 53(4): 526-536
Suman S, Datta K, Doiron K, Ren C, Kumar R, Taft DR, Fornace AJ, Jr., Maniar M, (2012) Radioprotective Effects of ON 01210.Na upon Oral Administration. Journal of Radiation Research 53(3): 368-376
Suman S, Maniar M, Fornace AJ, Jr., Datta K (2012) Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response. Radiation Oncology 7(1): 6-14
Tamhane M, Maniar M, Ren C, Benzeroul KE, Taft DR (2012) Disposition of ON 01210.Na (Ex-RAD®), a Novel Radioprotectant, in the Isolated Perfused Rat Liver: Probing Metabolic Inhibition to Increase Systemic Exposure. J Pharmaceut Sci: ePub 4Dec2012
Chun AW, Freshwater RE, Taft DR, Gillum AM, Maniar M (2011) Effects of formulation and route of administration on the systemic availability of Ex-RAD®, a new radioprotectant, in preclinical species. Biopharmaceutics & Drug Disposition 32(2): 99-111
Ghosh SP, Perkins MW, Hieber K, Kulkarni S, Kao TC, Reddy EP, Reddy MVR, Maniar M, Seed T, Kumar KS (2009) Radiation protection by a new chemical entity, Ex- RAD™: efficacy and mechanisms. Radiat Res 171(2): 173-179
Fernandes PP, Maniar M, Dash AK (2007) Development and validation of a sensitive liquid chromatographic method for the analysis of a novel radioprotectant: ON 01210.Na. J Pharm Biomed Anal 43(5): 1796-1803
Reviews and Editorials:
Singh VK, Ducey EJ, Brown DS, Whitnall MH (2012) A review of radiation countermeasure work ongoing at the Armed Forces Radiobiology Research Institute. International journal of radiation biology 88(4): 296-310
Thayer AM (2012) The Drugs That May Never Be Used. Chemical & Engineering News 90(26): 23-26
Willyard C (2011) Nuclear leak reinforces need for drugs to combat radiation. Nat Med 17(4): 391
