U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

Showing 51 - 60 of 2615 results

Status:
First approved in 2020

Class (Stereo):
CHEMICAL (ABSOLUTE)

TUCATINIB (ONT-380 or ARRY-380) is an orally active, reversible and selective small-molecule HER2 inhibitor invented by Array and licensed to Cascadian Therapeutics (previously named Oncothyreon) for development, manufacturing and commercialization. HER2, a growth factor receptor that is over-expressed in multiple cancers, including breast, ovarian, and stomach cancer. HER2 mediates cell growth, differentiation and survival, and tumors that overexpress HER2 are more aggressive and historically have been associated with poorer overall survival compared with HER2-negative cancers. ONT-380 is highly active as a single agent and in combination with both chemotherapy and Herceptin® (trastuzumab) in xenograft models of HER2+ breast cancer, including models of CNS metastases that were refractory to Tykerb® (lapatinib) or neratinib treatment. In a Phase 1 single agent clinical study, ONT-380 administered orally twice a day was well tolerated and demonstrated anti-tumor activity in heavily pre-treated HER2+ breast cancer patients with metastatic disease. Based on the strength of these preclinical and clinical trials, ONT-380 is advancing in one Phase 2 and three Phase 1b combination trials in patients with metastatic breast cancer. A second study reported the CNS activity of ONT-380 in combination with either T-DM1 or trastuzumab or capecitabine. Patients with brain metastases assessable for response were included in the combined analysis. Responses and clinical benefit in the CNS were reported with the three combinations tested, supporting future development of the drug for this particular indication.

Class (Stereo):
CHEMICAL (ACHIRAL)



Fostemsavir (BMS-663068) is an investigational attachment inhibitor with a unique mechanism of action. It is a prodrug of temsavir, which binds to HIV envelope glycoprotein 120 (gp120), thereby preventing viral attachment to the host CD4 cell surface receptor. In the absence of effective binding of HIV gp120 with the host CD4 receptor, HIV does not enter the host cell. Because fostemsavir has a novel mechanism of action, the drug should have full activity against HIV strains that have developed resistance to other classes of antiretroviral medications. In a phase 2b study of treatment-experienced individuals, fostemsavir appeared to be well tolerated. Phase 3 studies are ongoing.
Osilodrostat (INN, USAN) (developmental code name LCI-699) is an orally active, non-steroidal corticosteroid biosynthesis inhibitor which is under development by Novartis for the treatment of Cushing's syndrome and pituitary ACTH hypersecretion (a specific subtype of Cushing's syndrome). Osilodrostat specifically acts as a potent and selective inhibitor of aldosterone synthase (CYP11B2) and at higher dosages of 11β-hydroxylase (CYP11B1). Osilodrostat decreases plasma and urinary aldosterone levels and rapidly corrects hypokalemia, in patients with primary aldosteronism and hypertension. At doses ≥1 mg o.d. Osilodrostat markedly increases 11-deoxycortisol plasma levels and blunts ACTH-stimulated cortisol release in ≈20% of patients, consistent with the inhibition of CYP11B1. In patients with resistant hypertension, Osilodrostat produces a non-significant reduction in blood pressure, possibly due to the increase in 11-deoxycortisol levels and the stimulation of the hypothalamic-pituitary-adrenal feedback axis. Because of the lack of selectivity, poor antihypertensive effect, and short half-life, the development of Osilodrostat as antihypertensive was halted. As of 2017, Osilodrostat is in phase III and phase II clinical trials for the treatment of pituitary ACTH hypersecretion and Cushing's syndrome, respectively.

Class (Stereo):
CHEMICAL (ABSOLUTE)



Cedazuridine is a specific cytidine deaminase (CDA) inhibitor that was approved in combination with decitabine for the treatment of variable forms of myelodysplastic syndrome (MDS). It is known that decitabine is rapidly metabolized by CDA prior to reaching systemic circulation when administered orally. Thus, cedazuridine by inhibition of CDA increases systemic exposure of decitabine.
Selpercatinib (LOXO-292, ARRY-192) is a potent and specific RET (c-RET) inhibitor that was granted accelerated FDA approval on May 8, 2020, for specific RET-driven cancer indications. It is currently marketed under the brand name RETEVMO™ by Loxo Oncology Inc.
Ozanimod (previously known as RPC-1063) is a selective immune-inflammatory modulator of the G protein-coupled receptors sphingosine 1-phosphate 1 and 5, which are part of the sphingosine 1-phosphate (S1P) receptor family. Treatment with S1P receptor modulators interferes with S1P signaling and blocks the response of lymphocytes (a type of white blood cell) to exit signals from the lymph nodes, sequestering them within the nodes. The result is a downward modulation of circulating lymphocytes and anti-inflammatory activity by inhibiting cell migration to sites of inflammation. Ozanimod is currently in phase III clinical trials for the treatment of relapsing multiple sclerosis (RMS) and ulcerative colitis, and also in phase II clinical trials to determine whether it is effective in the treatment of Crohn's disease.
Lurbinectedin (PM-01183) - is a synthetic tetrahydropyrrolo [4, 3, 2-de]quinolin-8(1H)-one alkaloid analogue with potential antineoplastic activity. Lurbinectedin covalently binds to residues lying in the minor groove of DNA, which may result in delayed progression through S phase, cell cycle arrest in the G2/M phase and cell death. Lurbinectedin is a novel anticancer agent currently undergoing late-stage (Phase II /III) clinical evaluation in platinum-resistant ovarian, BRCA1/2-mutated breast and small-cell lung cancer. Lurbinectedin is structurally related to trabectedin and it inhibits active transcription and the DNA repair machinery in tumour cells.
Artesunate (AS) is a medication used to treat malaria. Although not FDA-approved for use in the United States, artesunate is used as the treatment of choice for severe malaria by the World Health Organization (WHO) over quinidine. Upon administration, artesunate is rapidly hydrolyzed to dihydroartemisinin, which is the most active schizonticidal metabolite. In hemoglobin-rich red blood cells, infected by plasmodia, endoperoxide bond of artesunate undergoes cleavage and releases a cascade of reactive intermediates-cytotoxic free radicals, which cause damage to parasites by alkylation of proteins and DNA.