Publications
ON 123300
PUBLICATIONS:
Deng, J, et al. (2018). “CDK 4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation.” Cancer Discovery, 8:2, 216-233.
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
Zhang X, Lv H, Zhou Q, Elkholi R, Chipuk JE, Reddy MV, Reddy EP, and Gallo JM. 2014) Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Mol Cancer Ther., 13: 1105–1116.
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
PUBLICATIONS:
Radke, K., Hansson, K., Sj̈ölund, J., et al. (2021). “Anti-tumor effects of rigosertib in high-risk neuroblastoma.” Translational Oncology 14, June 2021.
Yan, C., Nabil, S., Yang, J., Richmond, A., et al. (2021). “Novel induction of CD40 expression by tumor cells with RAS/RAF/PI3K pathway inhibition augments response to checkpoint blockade.” Molecular Cancer 20:85, June 2021.
Baker SJ, Cosenza SC, Athuluri-Divakar S, Reddy MVR, Vasquez-Del Carpio R, Jain R, Aggarwal AK, Reddy EP. (2020) A Contaminant Impurity, Not Rigosertib, Is a Tubulin Binding Agent. Mol Cell. 79: 180-190.
Günther JK, Nikolajevic A, Ebner S, Troppmair J, and Khalid S. Rigosertib-Activated JNK1/2 Eliminate Tumor Cells through p66Shc Activation (2020). Rigosertib-activated JNK1/2 eliminate tumor cells through p66Shc activation. Biology 9, 1-10.
Liu, Z., Wang, M., Wang, H., Fang, L., and Gou S. (2020). Platinum-based modification of styrlbenzylsulfones as multifunctional antitumor agents: Targeting the RAS/RAF pathway, enhancing antitumor activity, and overcoming multidrug resistance. J. Med. Chem. 63, 186-204.
Kowalczyk, J.T., Xiaolin, W, Hernandez, E.R., et al. (2020). “Rigosertib induces mitotic arrest and apoptosis in RAS-mutated rhabdomyosarcoma and neuroblastoma.: AACR Journals, Nov 2020.
Navada, S.C., Garcia-Manero, G., et al. (2020). “Rigosertib in combination with azacitidine in patients with myelodysplastic syndromes or acute myeloid leukemia: Results of a phase 1 study.” Leuk Res 94, June 2020
Baker SJ, Cosenza SC, Ramana Reddy MV, Premkumar Reddy E. (2019) Rigosertib ameliorates the effects of oncogenic KRAS signaling in a murine model of myeloproliferative neoplasia. Oncotarget. 20: 932-1942.
Atanasova, VS., Pourreyron, C., Farshchian, M., Lawler, M., Brown IV, CA., Watt, SA., Wright, S., Warkala, M., Guttman-Gruber, C., Hofbauer, JP., Fuentes, I., Prisco, M., Rashidghamat, E., Has, C., Salas-Alanis, JC., Pallison, F., Hovnanian, A., McGrath, JA., Mellerio, JE., Bauer, JW., and South, AP. (2019). Identification of rigosertib for the treatment of recessive dystrophic epidermolysis bullosa–associated squamous cell carcinoma. Clin. Cancer Res. 25, 3384-3391.
Navada, S.C., Fruchtman, S.M., et al. (2018). “A phase 1/2 study of rigosertib in patients with myelodysplastic syndromes (MDS) and MDS progressed to acute myeloid leukemia.” Leuk Res 64, 10-16.
Prasad A, Khudaynazar N, Tantravahi RV, Gillum AM, Hoffman BS. (2016) ON 01910.Na (rigosertib) inhibits PI3K/Akt pathway and activates oxidative stress signals in head and neck cancer cell lines. Oncotarget. 48: 79388-79400.
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.
Flemming, A. (2016) “RAS mimetic revealed.” Research Highlights Nature Reviews Drug Discovery, published online June 1.
Divakar, S.K., Vasquez-DelCarpio R., et al. (2016). "A small molecule RAS-mimetic disrupts RAS association with effector proteins to block signaling." Cell 165, 643-655, April 21.
Garcia-Manero, G., Fenaux, P., et al. (2016). “Rigosertib versus best supportive care for patients with high-risk myelodysplastic syndromes after failure of hypomethylating drugs (ONTIME): a randomised, controlled, phase 3 trial.” Lancet Oncology 17:4, 496-508, April 2016.
Alessandrino, E. (2016). “Novel trial designs for high-risk myelodysplastic syndromes.” Lancet Oncology 17:4, 410-412, April 2016.
Raza, A., Ali, A., Reddy, M. V. R., et al. (2016). “Rigosertib in myelodysplastic syndromes (MDS).” Expert Opinion on Orphan Drugs, published online July 28.
Navada, S. & Silverman, L. (2016) “The safety and efficacy of rigosertib in the treatment of Myelodysplastic syndromes.” Expert Review of Anticancer Therapy, 16:8, 805-810, July 2016.
Ritt, DA., Abreu-Blanco, MT., Bindu, L., Stephen, AG., Holderfield, M., and Morrison, DK (2016). Inhibition of Ras/Raf/MEK/ERK pathway signaling by a stress-induced phosphor-regulatory circuit. Molecular Cell. 64, 875-887.
Hyoda, T., Tsujioka, T., Nakahara, T., Suemori, S., Okamoto, S., Kataoka, M., and Tohyama, K. (2015). Rigosertib induces cell death of a myelodysplastic syndrome-derived cell line by DNA damage-induced G2/M arrest. Cancer Sci. 106, 287–293.
Xu, F., He, Q., Li, X., Chang, C.K., Wu, L.Y., Zhang, Z., Liu, L., Shi, W.H., Zhu, Y., Zhao, Y.S., et al. (2014). Rigosertib as a selective anti-tumor agent can ameliorate multiple dysregulated signaling transduction pathways in high- grade myelodysplastic syndrome. Sci. Rep. 4, 7310.
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.
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.
Prasad, A., Park, I.W., Allen, H., Zhang, X., Reddy, M.V., Boominathan, R., Reddy, E.P., and Groopman, J.E. (2009). Styryl sulfonyl compounds inhibit translation of cyclin D1 in mantle cell lymphoma cells. Oncogene 28, 1518– 1528.
Gumireddy, K., Reddy, M.V., Cosenza, S.C., Boominathan, R., Baker, S.J., Papathi, N., Jiang, J., Holland, J., and Reddy, E.P. (2005). ON01910, a non- ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent. Cancer Cell 7, 275–286.
ABSTRACTS PRESENTED AT SCIENTIFIC CONFERENCES:
25th Congress of the European Hematology Association Virtual Event (June 2020)
Takahaski, K. et al. (2020) Mutations in RAS Pathway Genes Correlate with Type of Failure to Azacitidine: Genomic Analysis at Randomization onto the INSPIRE trial (Oral Presentation Slides and Poster)
61st American Society of Hematology Annual Meeting (December 2019)
Navada S., et al. (2019) Phase II Study of Oral Rigosertib Combined with Azacitidine as First-Line Therapy in Patients with Higher Risk MDS (Oral Presentation Slides)
Garcia-Manero G., et al. (2019) Genomic Profiling in Patients with Higher Risk MDS Following HMA Failure: Baseline Results from the INSPIRE Study (04-30) (Poster)
Garcia-Manero G., et al. (2019) Phase 2/3, Multi-Center, Int’l, Randomized, Double-Blind, Placebo Controlled Study of Oral Rigosertib + Injectable Azacitidine (AZA) Versus Injectable AZA in Treatment-Naïve Patients with Higher Risk MDS (Poster)
Jonasova A., et al. (2019) The INSPIRE Study in Higher Risk MDS: A Novel Phase 3 Study Adaptive Design for Hematological Malignancies in Adults (Poster)
Rai R., et al. (2019) The Sequenced Combination of Rigosertib and Azacitidine Has Modulatory Effects on CXCL8, RIG-I Like Receptor and Wnt/β-Catenin Signaling and Downstream Hematopoiesis Pathways in an In-Vitro Model of the MDS (Poster)
24th Congress of the European Hematology Association in Amsterdam (June 2019)
Navada, S. et al. (2019) Phase II Study of Oral Rigosertib Combined with Azacitidine in Patients with Higher-Risk Myelodysplastic Syndromes (MDS) (Oral Presentation Slides)
15th International Symposium on Myelodysplastic Syndromes in Copenhagen (May 2019)
Navada, S. et al. (2019) Phase II Study of Oral Rigosertib Combined with Azacitidine in Patients with Higher-Risk Myelodysplastic Syndromes (MDS) (Poster)
Richa R, et al. (2019) Rigosertib (RIG) modulates MAPK and hematopoiesis signaling and synergizes Azacitidine (AZA) altering viral mimicry pathway in myelodysplastic syndrome (MDS) (Poster)
Silverman, L. et al. (2019) Emergence of PTPN11 mutations is associated with Clinical Resistance to the Combination of Azacitidine and Rigosertib in patients with Higher-Risk Myelodysplastic Syndrome (Poster)
Al-Kali, A. et al. (2019) Utility of Adaptive Trial Design in Higher-Risk Myelodysplastic (HR-MDS) Syndromes in a Phase 3 Trial of Intravenous Rigosertib: INSPIRE Trial (Poster)
Santaguida, M. et al. (2019) Ex-Vivo Response Profiling of Rigosertib Identifies Distinct Classes of Responders in Myelodysplastic Syndrome (Abstract)
Acute Leukemia Forum in Newport Beach, CA (April 2019)
Navada, S., et al. (2019) Phase II Study of Oral Rigosertib Combined with Azacitidine in Patients with Higher-Risk Myelodysplastic Syndromes (MDS) (Oral Presentation Slides)
Navada, S., et al. (2019) Oral Rigosertib Combined with Azacitidine in Patients with Acute Myeloid Leukemia (AML) (Poster)
Al-Kali, A., et al. (2019) Utility of Adaptive Trial Design in a Higher-Risk Myelodysplastic (HR-MDS) Syndromes Phase 3 Trial of Intravenous Rigosertib: INSPIRE Trial (Poster)
ACCR Annual Meeting 2019
Yan, C., et al. (2019) Rigosertib, a Ras Mimetic, Inhibits Melanoma Cell Viability and Synergizes with Anti-PD1 to Promote Anti-tumor Immune Responses (Poster)
60th American Society of Hematology Annual Meeting 2018
Navada, S., et al. (2018) Phase 2 Expansion Study of Oral Rigosertib Combined with Azacitidine (AZA) in Patients with Higher-Risk (HR) Myelodysplastic Syndromes: Efficacy and Safety Results in HMA Treatment Naive & Relapsed/Refractory Patients (Oral Presentation Slides)
Roboz, J., et al. (2018) Truncation Products of Stromal Cell Derived Factor-1 (CXCL12) Quantified By Mass Spectrometry in Patients with Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) Treated with Rigosertib in a Phase I-II Study (Poster)
Maniar, M., et al. Evaluation of Underlying Cause of Genitourinary (GU) Adverse Events (AEs) in Patients with Myelodysplastic Syndromes upon Oral Administration of Rigosertib: Safety and Pharmacokinetic Analysis of Rigosertib across Three Clinical Trials (Poster)
Taft, D., et al. (2018) Amelioration of Rigosertib Treatment Related Genitourinary Adverse Events in Patients with Myelodysplastic Syndromes: Implementation of Novel Dosing Regimen Derived through Pharmacokinetic Modeling in Phase 2 Study of Oral Rigosertib in Combination with Azacitidine (AZA) (Poster)
