A5071396195- Immune Cell Function and Interaction
- Synthetic Organic Chemistry Methods
- X-ray Diffraction in Crystallography
- Immunotherapy and Immune Responses
- Crystallization and Solubility Studies
- T-cell and B-cell Immunology
- Chronic Lymphocytic Leukemia Research
- Microbial Natural Products and Biosynthesis
- Immune cells in cancer
- Biochemical and Molecular Research
- PI3K/AKT/mTOR signaling in cancer
- Synthesis and Catalytic Reactions
- Marine Sponges and Natural Products
- Viral-associated cancers and disorders
- Lymphoma Diagnosis and Treatment
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Chemokine receptors and signaling
- Cancer Treatment and Pharmacology
- Peroxisome Proliferator-Activated Receptors
- Cancer, Lipids, and Metabolism
- interferon and immune responses
- Cancer-related molecular mechanisms research
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and Reactions of Organic Compounds
- Asymmetric Synthesis and Catalysis
APT Therapeutics (United States)
2019-2024
Rapt Therapeutics (United States)
2019-2024
Baylor University
2019
Texas A&M University
2012-2019
Mitchell Institute
2014
Tecnológico de Monterrey
2012
Emory University
2007-2009
Background Checkpoint inhibitors (CPIs) such as anti-PD(L)-1 and anti-CTLA-4 antibodies have resulted in unprecedented rates of antitumor responses extension survival patients with a variety cancers. But some fail to respond or initially but later relapse they develop resistance immune therapy. One the tumor-extrinsic mechanisms for therapy is accumulation regulatory T cells (T reg ) tumors. In preclinical clinical studies, it has been suggested that tumor trafficking mediated by CC...
The Epstein-Barr Virus (EBV) is involved in the etiology of multiple hematologic and epithelial human cancers. EBV+ tumors employ immune escape mechanisms, including recruitment immunosuppressive regulatory T cells (Treg). Here, we show some tumor express high levels chemokines CCL17 CCL22 both vitro vivo that this expression mirrors EBV LMP1 gene vitro. Patient samples from lymphoblastic (Hodgkin lymphoma) (nasopharyngeal carcinoma; NPC) revealed cell-intrinsic -extrinsic origin, depending...
The C–C chemokine receptor 4 (CCR4) is broadly expressed on regulatory T cells (Treg) as well other circulating and tissue-resident cells. Treg can be recruited to the tumor microenvironment (TME) through chemokines CCL17 CCL22. accumulation in TME has been shown dampen antitumor immune response thought an important driver evasion. Preclinical clinical data suggest that reducing population potentiate of checkpoint inhibitors. We have developed small-molecule antagonists CCR4, featuring a...
Recruitment of suppressive CD4+ FOXP3+ regulatory T cells (Treg) to the tumor microenvironment (TME) has potential weaken antitumor response in patients receiving treatment with immuno-oncology (IO) agents. Human Treg express CCR4 and can be recruited TME through CC chemokine ligands CCL17 CCL22. In some cancers, accumulation correlates poor patient prognosis. Preclinical data suggests that preventing recruitment increasing population activated effector (Teff) potentiate immune responses. We...
A highly convergent synthesis of fostriecin is described, featuring sequential palladium-catalyzed Negishi cross couplings to form the C7-C8 bond and C8-methyl bond, followed by late-stage regio- stereoselective dihydroxylation C8-C9.
A modular approach to the synthesis of complex polyketide natural products is demonstrated for C9-C27 degradation product from aflastatin A. The cross-coupling C23-C27 terminal alkyne with C17-C22 epoxide underwent functionalization resulting internal alkyne, which was then coupled similarly C9-C16 epoxide. This concluded regio- and stereoselective addition methyl onto followed by hydroboration-oxidation.
Cyclopropanations of alkene-containing natural products that proceed under mild conditions are reported for simultaneous arming and structure–activity relationship studies. An alkynyl diazo ester Rh(II) catalysis is employed cyclopropanations electron-rich olefins while an sulfonium ylide used electron-poor olefins. This approach enables product derivatization SAR studies (i.e., via alkyne attachment) subsequent conjugation with reporter tags (e.g., biotin, fluorophores, photoaffinity...
General control nonderepressible 2 (GCN2) protein kinase is a cellular stress sensor within the tumor microenvironment (TME), whose signaling cascade has been proposed to contribute immune escape in tumors. Herein, we report discovery of cell-potent GCN2 inhibitors with excellent selectivity against its closely related Integrated Stress Response (ISR) family members heme-regulated inhibitor (HRI), R (PKR), and (PKR)-like endoplasmic reticulum (PERK), as well good kinome-wide favorable PK. In...
A concise approach to the synthesis of homobenzotetramisole and derivatives is described. Our strategy features a one-pot acylation-cyclization 2-aminobenzothiazole with α,β-unsaturated acid chlorides afford annulated pyrimidones. Subsequent Grignard addition followed by acid-promoted dehydration reduction provides good overall yields title compounds in three steps quantities up 10 g. The employs low-cost readily available starting materials enables access both optical antipodes these...
Abstract Naturally suppressive CD4+ Foxp3+ Treg are essential for immune tolerance. Although Treg-mediated suppression of effector cells is important to control inflammation and prevent autoimmune diseases, the presence in tumor microenvironment (TME) has been shown dampen anti-tumor responses. Human express CCR4, receptor chemokines CCL17 CCL22. These produced by cells, tumor-associated macrophages dendritic as well T (Teff). Preclinical clinical data supports a role CCR4-mediated...
Abstract Hematopoietic progenitor kinase 1 (HPK1) has been shown to act as a negative regulator of T cell receptor signaling and subsequent effector function. Inhibiting HPK1 enhance activity emerged promising strategy for cancer immunotherapy. Upon engagement, the domain is activated targets components (TCR) pathway degradation, including SLP76. However, molecular events connecting observed functions downstream proximal TCR are not well understood. Through transcriptional profiling...
Abstract Type 2 helper T cells (Th2)cells have been shown to express CCR4 receptor, and play a critical role in driving the pathogenesis of asthma atopic dermatitis. FLX193 is best-in-class, highly-potent selective small molecule antagonist under investigation for treatment allergic disorders. blocked migration CCR4+ Th2 (human mouse) towards CCL17 CCL22 an vitro chemotaxis assay. well-tolerated animals at efficacious doses. In Ovalbumin (OVA)-induced model, significantly reduced lymphocyte...
Abstract Review: 81 refs.
ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to "Concise Synthesis of the Isothiourea Organocatalysts Homobenzotetramisole and Derivatives"Beatrice Ranieri, Omar Robles, Daniel Romo*Cite this: J. Org. Chem. 2013, 78, 16, 8215Publication Date (Web):August 2, 2013Publication History Published online2 August 2013Published inissue 16 2013https://pubs.acs.org/doi/10.1021/jo4015485https://doi.org/10.1021/jo4015485correctionACS...
Abstract We have performed experiments to test whether Epstein Barr Virus (EBV)-infected tumors are enhanced for regulatory T cell (Treg) infiltration and selective potent CCR4 antagonists would be a particularly effective therapeutic in this class of indications. Treg cells, which contribute an immune-suppressive tumor microenvironment (TME), attracted via the recognition CCL17 CCL22 ligands by receptor. These chemokines been shown expressed cells infected (EBV) viral LMP1 gene. Tumor types...
The viability of chronic lymphocytic leukemia (CLL) is critically dependent upon staving off death by apoptosis, a hallmark CLL pathophysiology. overexpression the Bcl-2 family proteins likely play major role in apoptosis blockade CLL, and has been an effective target therapy. recognition that Mcl-1, component anti-apoptotic response, intrinsically short-lived must be continually resynthesized suggested novel therapeutic approach. Pateamine A (PatA), macrolide marine natural product,...
Abstract The viability of chronic lymphocytic leukemia (CLL) is critically dependent upon staving off death by apoptosis, a hallmark CLL pathophysiology. overexpression the Bcl-2 family proteins likely play major role in apoptosis blockade CLL, and has been an effective target therapy. recognition that Mcl-1, component anti-apoptotic response, intrinsically short-lived must be continually resynthesized suggested novel therapeutic approach. Pateamine A (PatA), macrolide marine natural...