NEWTOWN, PA, United States
NEWTOWN, PA, United States

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Patent
Temple University and Onconova Therapeutics, Inc. | Date: 2017-03-08

Substituted phenol derivatives of Formula I:


Patent
Onconova Therapeutics, Inc. | Date: 2015-05-15

An aqueous pharmaceutical solution composition comprising between about 20 mg/ml to about 100 mg/ml of a radioprotective ,-unsaturated aryl sulfone, a cosolvent comprising polyethylene glycol (PEG), polypropylene glycol, polyglycerol, DMA, propylene glycol, glycerol, ethanol, sorbitol, isopropyl alcohol, or a combination thereof in an amount between about 25% and about 90% w/v, and a water soluble Vitamin E derivative, wherein the composition has a pH within the range of about 7.0 to about 9.5.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 275.86K | Year: 2011

DESCRIPTION (provided by applicant): The recent success of imatinib for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia has made tyrosine and serine/threonine kinases as major targets for cancer therapy. Currently, since only a small fraction of the human kinome has been targeted by reasonably selective and potent inhibitors, there is an urgent need to develop strategies for efficient discovery and optimization of new inhibitors. Towards this goal, we have recently developeda compound library of candidate ATP-competitive kinase inhibitors. We screened our collection of novel small molecules (approximately 2,000) against a panel of 16 cultured tumor cell lines for the ability to induce cell death. This search revealed one compound, ON 1231320, with remarkable cytotoxicity against the entire panel of 16 tumor cell lines. Kinase inhibition assays against a panel of 285 kinases revealed that this compound had a remarkable specificity towards Polo-like kinase 2 (Plk2 or Snk), a kinase involved in centrosome duplication and mitotic progression. As expected, tumor cells treated with ON 1231320 arrest in mitosis due to abnormal microtubule spindle development. Plk2 has recently been implicated as one of the kinases that links cellularmetabolism to the cell cycle. Mitochondrial dysfunction, with resulting increased dependence on glycolysis, is frequently observed in cancer cells (known as the Warburg effect). Identification of pathways that promote cell survival under conditions of mitochondrial dysfunction has therapeutic implications. In a recent study, it has been shown that targeted ablation of the SCO2 gene in HCT116 human colon cancer cell line results in the ablation of mitochondrial respiration and that PLK2 is the most highly expressed gene in SCO2-/-cells. Furthermore, even a modest reduction in Plk2 levels in human cancer cells with defects in mitochondrial respiration results in the elimination of their ability to form xenografts in mice. In this proposal, we plan to furtherexamine this potent and selective Plk2 inhibitor in order to determine important chemical characteristics and biological activity necessary for advanced pre-clinical development. We propose to study the effects of this compound on tumor growth in vitro andin vivo to determine how ON 1231320 will serve as a novel cancer chemotherapeutic. The aims of this proposal are to: (1) Prepare an optimal formulation of ON 1231320 for stability and parenteral delivery; (2) Characterize the pharmacokinetic and pharmacodynamic properties of ON 1231320 in non-tumor and tumor-bearing mice; and (3) Evaluate anti-tumor efficacy of ON 01231320, determine the degree of inhibition of Plk2 required for inhibition of human tumor growth in xenograft models, and assess how ON 1231320 doses and schedules are related to the anti-tumor activity of the compound. PUBLIC HEALTH RELEVANCE: This application describes the discovery of a novel cancer therapeutic, ON 1231320, which could find a wide application in the treatment of someof the most difficult-to-treat cancers that are traditionally resistant to chemotherapy. ON 1231320 has a unique and targeted anti-cancer mechanism of action. In this application, we propose to develop optimal formulation, preclinical pharmacology, and anti-cancer efficacy profiles for ON 1231320 in preparation for a Phase I study in cancer patients.


The invention discloses a diagnostic method for predicting the therapeutic efficacy of a broad specificity kinase inhibitor in a subject with refractory cancer comprising determining the locus-specific DNA methylation profile of the subject, wherein the locus-specific DNA methylation profile predicts the therapeutic efficacy of a broad specificity kinase inhibitor for treatment of a subject with refractory cancer.


Patent
Onconova Therapeutics, Inc. | Date: 2011-03-24

The present invention provides compositions and methods for promoting rapid healing and/or regeneration of damaged tissue resulting from a wound comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a compound of (E)-4-carboxystyryl-4-chlorobenzylsulfone, or a functional derivative thereof, and a pharmaceutically acceptable excipient.


Patent
Onconova Therapeutics, Inc. | Date: 2011-03-24

An aqueous pharmaceutical solution composition comprising between about 20 mg/ml to about 100 mg/ml of a radioprotective ,-unsaturated aryl sulfone, a cosolvent comprising polyethylene glycol (PEG), polypropylene glycol, polyglycerol, DMA, propylene glycol, glycerol, ethanol, sorbitol, isopropyl alcohol, or a combination thereof in an amount between about 25% and about 90% w/v, and a water soluble Vitamin E derivative, wherein the composition has a pH within the range of about 7.0 to about 9.5.


Patent
Onconova Therapeutics, Inc. | Date: 2015-04-29

Solution and suspension formulations are provided for administration prior to or after exposure to ionizing radiation for reducing toxic effects of the radiation in a subject which comprises an effective amount of at least one radioprotective , unsaturated aryl sulfone wherein the composition has a pH within the range of about 8 to about 9.


Patent
Onconova Therapeutics, Inc. | Date: 2014-08-27

Solution and suspension formulations are provided for administration prior to or after exposure to ionizing radiation for reducing toxic effects of the radiation in a subject which comprises an effective amount of at least one radioprotective , unsaturated aryl sulfone wherein the composition has a pH within the range of about 8 to about 9.


Patent
Onconova Therapeutics, Inc. and Columbia University | Date: 2013-12-06

The invention discloses a method of treating cancer refractory to an anticancer agent comprising administering to a cancer patient a pharmaceutical composition comprising at least one compound of Formula 1 Where R_(1 )is selected from the group consisting of NH_(2), NHCH_(2)COOH, NHCH(CH_(3))COOH, NHC(CH_(3))_(2)COOH, NHCH_(2)CH_(2)OH and N(CH_(2)CH_(2)OH)_(2 )or a pharmaceutically acceptable salt of such a compound, and an anticancer agent.


News Article | March 2, 2017
Site: globenewswire.com

NEWTOWN, Pa., March 02, 2017 (GLOBE NEWSWIRE) -- Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 clinical stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, today announced that Company management will present an overview at: About Onconova Therapeutics, Inc. Onconova Therapeutics, Inc. is a Phase 3 stage biopharmaceutical company focused on discovering and developing novel small molecule drug candidates to treat cancer, with a primary focus on Myelodysplastic Syndromes (MDS). Rigosertib, Onconova’s lead candidate, is a proprietary phase 3 small molecule agent, which blocks cellular signaling by targeting RAS effector pathways.  Using a proprietary chemistry platform, Onconova has created a pipeline of targeted anti-cancer agents designed to work against specific cellular pathways that are important in cancer cells, while causing minimal damage to normal cells. Onconova has three product candidates in clinical trials and several active pre-clinical programs. Advanced clinical trials with our lead compound, rigosertib, are aimed at unmet medical needs of patients with MDS. For more information, please visit http://www.onconova.com. Forward Looking Statements Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties. These statements relate to future events or Onconova Therapeutics, Inc.'s future operations, clinical development of Onconova's product candidates and presentation of data with respect thereto, regulatory approvals, expectations regarding the sufficiency of Onconova's cash and other resources to fund operating expenses and capital expenditures, Onconova's anticipated milestones and future expectations and plans and prospects. Although Onconova believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. Onconova has attempted to identify forward-looking statements by terminology including "believes," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "should," "approximately" or other words that convey uncertainty of future events or outcomes. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including Onconova's need for additional financing and current plans and future needs to scale back operations if adequate financing is not obtained, the success and timing of Onconova's clinical trials and regulatory approval of protocols, and those discussed under the heading "Risk Factors" in Onconova's most recent Annual Report on Form 10-K and quarterly reports on Form 10-Q. Any forward-looking statements contained in this release speak only as of its date. Onconova undertakes no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events. GENERAL CONTACT: http://www.onconova.com/contact/ INVESTOR RELATIONS CONTACT: Lisa Sher, MBS Value Partners on behalf of Onconova Therapeutics Lisa.Sher@mbsvalue.com / (212) 750-5800

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