Orally Bioavailable Small Molecule CD73 Inhibitor (OP-5244) Reverses Immunosuppression Through Blockade of Adenosine Production.
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DOI: 10.1021/acs.jmedchem.0c01086
Abstract: The adenosinergic pathway represents an attractive new therapeutic approach in cancer immunotherapy. In this pathway, ecto-5-nucleotidase CD73 has the unique function of regulating production of immunosuppressive adenosine (ADO) through the hydrolysis of AMP. CD73 is… read more here.
Keywords: orally bioavailable; production; cd73 inhibitor; small molecule ... See more keywords
Discovery of a Potent and Orally Bioavailable Melatonin Receptor Agonist.
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DOI: 10.1021/acs.jmedchem.0c01836
Abstract: To develop potent and orally bioavailable melatonin receptor (MT1 and MT2) agonists, a novel series of 5-6-5 tricyclic derivatives was designed, synthesized, and evaluated. The synthesized indeno[5,4-d][1,3]oxazole, cyclopenta[c]pyrazolo[1,5-a]pyridine, indeno[5,4-d][1,3]thiazole, and cyclopenta[e]indazole derivatives showed potent binding… read more here.
Keywords: potent orally; orally bioavailable; bioavailable melatonin; melatonin receptor ... See more keywords
Discovery of a Pyrimidinedione Derivative as a Potent and Orally Bioavailable Axl Inhibitor.
Sign Up to like & getrecommendations! Published in 2021 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.0c02093
Abstract: The receptor tyrosine kinase Axl plays important roles in promoting cancer progression, metastasis, and drug resistance and has been identified as a promising target for anticancer therapeutics. We used molecular modeling-assisted structural optimization starting with… read more here.
Keywords: potent orally; orally bioavailable; axl; bioavailable axl ... See more keywords
Discovery and Development of a Potent, Selective, and Orally Bioavailable CHK1 Inhibitor Candidate: 5-((4-((3-Amino-3-methylbutyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)picolinonitrile.
Sign Up to like & getrecommendations! Published in 2021 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c00994
Abstract: Checkpoint kinase 1 (CHK1) plays an important role in the DNA damage response pathway, being a potential anti-cancer drug target. In this study, we used a strategy for trifluoromethyl substitution to obtain orally bioavailable CHK1… read more here.
Keywords: chk1; orally bioavailable; amino; chk1 inhibitor ... See more keywords
Structural Feature Analyzation Strategies toward Discovery of Orally Bioavailable PROTACs of Bruton's Tyrosine Kinase for the Treatment of Lymphoma.
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DOI: 10.1021/acs.jmedchem.2c00324
Abstract: Bruton's tyrosine kinase proteolysis-targeting chimeras (BTK-PROTACs) have emerged as a promising approach to address the limitations of BTK inhibitors. However, conducting the rational discovery of orally bioavailable BTK-PROTACs presents significant challenges. In this study, dimensionality… read more here.
Keywords: btk protacs; discovery orally; bruton tyrosine; orally bioavailable ... See more keywords
Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306.
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DOI: 10.1021/acs.jmedchem.2c00552
Abstract: PKMYT1 is a regulator of CDK1 phosphorylation and is a compelling therapeutic target for the treatment of certain types of DNA damage response cancers due to its established synthetic lethal relationship with CCNE1 amplification. To… read more here.
Keywords: pkmyt1 inhibitor; pkmyt1; discovery orally; orally bioavailable ... See more keywords
Orally Bioavailable Prodrugs of ψ-GSH: A Potential Treatment for Alzheimer's Disease.
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DOI: 10.1021/acs.jmedchem.2c00779
Abstract: Addressing glycation-induced oxidative stress in Alzheimer's disease (AD) is an emerging pharmacotherapeutic strategy. Restoration of the brain glyoxalase enzyme system that neutralizes reactive dicarbonyls is one such approach. Toward this end, we designed, synthesized, and… read more here.
Keywords: gsh potential; alzheimer disease; orally bioavailable; prodrugs gsh ... See more keywords
Discovery of Hexahydrofuro[3,2-b]furans as New Kinase-Selective and Orally Bioavailable JAK3 Inhibitors for the Treatment of Leukemia Harboring a JAK3 Activating Mutant.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c00922
Abstract: Janus kinase 3 (JAK3) is a potential target for the treatment of hematological malignancies. Herein, we report the discovery of a series of new orally bioavailable irreversible JAK3 kinase inhibitors. The representative compound 12n potently… read more here.
Keywords: orally bioavailable; kinase; leukemia; treatment ... See more keywords
Discovery of Orally Bioavailable SOS1 Inhibitors for Suppressing KRAS-Driven Carcinoma.
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DOI: 10.1021/acs.jmedchem.2c00986
Abstract: The interaction between son of sevenless 1 (SOS1) gene and Kirsten rat sarcoma viral oncogene (KRAS) is crucial for activating signals of proliferation and survival in a range of cancers. We previously discovered compound 40a… read more here.
Keywords: bioavailable sos1; orally bioavailable; kras driven; suppressing kras ... See more keywords
Identification of RP-6685, an Orally Bioavailable Compound that Inhibits the DNA Polymerase Activity of Polθ.
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DOI: 10.1021/acs.jmedchem.2c00998
Abstract: DNA polymerase theta (Polθ) is an attractive synthetic lethal target for drug discovery, predicted to be efficacious against breast and ovarian cancers harboring BRCA-mutant alleles. Here, we describe our hit-to-lead efforts in search of a… read more here.
Keywords: identification 6685; dna polymerase; pol; orally bioavailable ... See more keywords
Discovery of CH7057288 as an Orally Bioavailable, Selective, and Potent pan-TRK Inhibitor.
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DOI: 10.1021/acs.jmedchem.2c01099
Abstract: Kinase fusions involving tropomyosin receptor kinases (TRKs) have been proven to act as strong oncogenic drivers and are therefore recognized as attractive therapeutic targets. We screened an in-house kinase-focused library and identified a promising hit… read more here.
Keywords: selective potent; orally bioavailable; bioavailable selective; trk inhibitor ... See more keywords