ABSTRACT
Exploring the scope of biocatalytic transformations in the absence of enzyme structures without extensive experimentation is a challenging task. To expand the limited substrate capacity of carrot-mediated bioreduction and hunt for new medicinally relevant ketones with minimum cost of labor and time, we deployed a practical method inspired by ligand-based drug design. Through analyzing collected literature data and building pharmacophore and reactivity prediction models, we screened a self-built virtual library of >8000 ketones bearing the most frequently used N,O,S-heterocycles and functional groups in drug discovery. Representative examples were validated, expanding the bioreduction substrate scope. The public availability of our models alongside the straightforward screening workflow makes it time-, labor-, and cost-saving to evaluate unknown bioreduction substrates for medicinal chemistry applications, especially for a large set of structurally differentiated ketones. Our studies also showcase the novelty of utilizing medicinal chemistry principles to solve a general biocatalysis problem.
Subject(s)
Drug Design , Ketones , Ligands , Ketones/chemistry , Ketones/metabolism , Oxidation-Reduction , Biocatalysis , Daucus carota/metabolism , Daucus carota/chemistryABSTRACT
The adsorption and dissociation of phosgene (COCl2) molecules on three kinds of rutile TiO2(110) surfaces (stoichiometric: TiO2-Sto; oxygen defective: TiO2-Ov; and substoichiometric: TiO1.875) were investigated based on density functional theory calculations. The nature of interactions between the COCl2 molecule and rutile TiO2(110) surfaces with different degrees of reduction was researched by the analysis of geometries, electron density difference, adsorption energies and density of states (DOS). Computational results show that COCl2 indicates instability and will dissociate directly without the presence of transition states on a substoichiometric TiO1.875(110) surface. The adsorption and dissociation behavior of COCl2 on the rutile surface is not only helpful in providing theoretical support for the clean and efficient degradation of COCl2, but also helpful in elucidating the role of COCl2 as an intermediate product in the carbochlorination of titanium ore.
ABSTRACT
The BET family of proteins consists of BRD2, BRD3, BRD4, and BRDt. Each protein contains two distinct bromodomains (BD1 and BD2). BET family bromodomain inhibitors under clinical development for oncology bind to each of the eight bromodomains with similar affinities. We hypothesized that it may be possible to achieve an improved therapeutic index by selectively targeting subsets of the BET bromodomains. Both BD1 and BD2 are highly conserved across family members (>70% identity), whereas BD1 and BD2 from the same protein exhibit a larger degree of divergence (â¼40% identity), suggesting selectivity between BD1 and BD2 of all family members would be more straightforward to achieve. Exploiting the Asp144/His437 and Ile146/Val439 sequence differences (BRD4 BD1/BD2 numbering) allowed the identification of compound 27 demonstrating greater than 100-fold selectivity for BRD4 BD2 over BRD4 BD1. Further optimization to improve BD2 selectivity and oral bioavailability resulted in the clinical development compound 46 (ABBV-744).
Subject(s)
Cell Cycle Proteins/antagonists & inhibitors , Cell Cycle Proteins/metabolism , Drug Discovery/methods , Pyridines/chemistry , Pyridines/metabolism , Pyrroles/chemistry , Pyrroles/metabolism , Transcription Factors/antagonists & inhibitors , Transcription Factors/metabolism , Animals , Female , HeLa Cells , Humans , Mice , Mice, SCID , Protein Domains/drug effects , Protein Domains/physiology , Protein Structure, Secondary , Protein Structure, Tertiary , Pyridines/pharmacology , Pyrroles/pharmacology , Xenograft Model Antitumor Assays/methodsABSTRACT
Proteins of the bromodomain and extra-terminal (BET) domain family are epigenetic readers that bind acetylated histones through their bromodomains to regulate gene transcription. Dual-bromodomain BET inhibitors (DbBi) that bind with similar affinities to the first (BD1) and second (BD2) bromodomains of BRD2, BRD3, BRD4 and BRDt have displayed modest clinical activity in monotherapy cancer trials. A reduced number of thrombocytes in the blood (thrombocytopenia) as well as symptoms of gastrointestinal toxicity are dose-limiting adverse events for some types of DbBi1-5. Given that similar haematological and gastrointestinal defects were observed after genetic silencing of Brd4 in mice6, the platelet and gastrointestinal toxicities may represent on-target activities associated with BET inhibition. The two individual bromodomains in BET family proteins may have distinct functions7-9 and different cellular phenotypes after pharmacological inhibition of one or both bromodomains have been reported10,11, suggesting that selectively targeting one of the bromodomains may result in a different efficacy and tolerability profile compared with DbBi. Available compounds that are selective to individual domains lack sufficient potency and the pharmacokinetics properties that are required for in vivo efficacy and tolerability assessment10-13. Here we carried out a medicinal chemistry campaign that led to the discovery of ABBV-744, a highly potent and selective inhibitor of the BD2 domain of BET family proteins with drug-like properties. In contrast to the broad range of cell growth inhibition induced by DbBi, the antiproliferative activity of ABBV-744 was largely, but not exclusively, restricted to cell lines of acute myeloid leukaemia and prostate cancer that expressed the full-length androgen receptor (AR). ABBV-744 retained robust activity in prostate cancer xenografts, and showed fewer platelet and gastrointestinal toxicities than the DbBi ABBV-07514. Analyses of RNA expression and chromatin immunoprecipitation followed by sequencing revealed that ABBV-744 displaced BRD4 from AR-containing super-enhancers and inhibited AR-dependent transcription, with less impact on global transcription compared with ABBV-075. These results underscore the potential value of selectively targeting the BD2 domain of BET family proteins for cancer therapy.
Subject(s)
Cell Cycle Proteins/antagonists & inhibitors , Cell Cycle Proteins/chemistry , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Protein Domains/drug effects , Pyridines/pharmacology , Pyrroles/pharmacology , Transcription Factors/antagonists & inhibitors , Transcription Factors/chemistry , Animals , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Enhancer Elements, Genetic/genetics , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Mice , Pyridines/adverse effects , Pyridines/toxicity , Pyrroles/adverse effects , Pyrroles/toxicity , Rats , Receptors, Androgen/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Transcription, Genetic/drug effects , Xenograft Model Antitumor AssaysABSTRACT
The interactions between Fe2SiO4 and ZnO play an essential role in the recovery of zinc from copper slag. The dissolution and substitution mechanism of ZnO in fayalite were investigated by using TG-DSC, XRD, PPMS DynaCool, XPS, Mossbauer and SEM-EDS analyses and compared with MS calculation results. The results indicate that the dissolution and substitution are actually processes of the penetrating dissolution of Zn(II) ions that can be divided into three steps: 1) ZnO dissociates into Zn1-yO and Zn(II) ions; 2) Zn(II) penetrates the gap of the octahedron outer layer to substitute Fe(II) sites in the internal structure of SiOFe(II) (M2) to form (Fe2-x, Znx)SiO4; 3) Fe(II) is forced to migrate to the surface of (Fe2-x, Znx)SiO4 to form (Zn1-y, Fe(II)y)O. These findings can be derived the occurrence state and distribution of zinc in copper slag theoretically.
ABSTRACT
A metallurgical material integration concept, using porous calcium titanate (CaTiO3) as raw material, was put forward for preparation of metallic titanium powder and porous titanium by calciothermic reduction. Porous metallic titanium was prepared by calcium vapor reduction at 1273â¯K for 6â¯h with two types of interconnected pores in titanium samples. The interconnected macropores about 50-300⯵m were inherited from porous CaTiO3, and the micropores about 5-40⯵m were made by leaching removal of byproduct CaO in reduction products. Metallic porous titanium was fabricated in Ca-dissolved CaO-CaCl2 molten salt mixtures by self-sintering and had a good interconnectivity inside with thickness about 155⯵m and the porosities of the porous titanium are 65-81%.
Subject(s)
Calcium/chemistry , Materials Testing , Titanium/chemistry , Image Processing, Computer-Assisted , Models, Theoretical , Porosity , Spectrometry, X-Ray Emission , Thermodynamics , X-Ray DiffractionABSTRACT
Novel conformationally constrained BET bromodomain inhibitors have been developed. These inhibitors were optimized in two similar, yet distinct chemical series, the 6-methyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-ones (A) and the 1-methyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-ones (B). Each series demonstrated excellent activity in binding and cellular assays, and lead compounds from each series demonstrated significant efficacy in in vivo tumor xenograft models.
Subject(s)
Nuclear Proteins/antagonists & inhibitors , Pyridones/chemistry , Transcription Factors/antagonists & inhibitors , Animals , Binding Sites , Cell Cycle Proteins , Cell Line, Tumor , Cell Proliferation/drug effects , Crystallography, X-Ray , Drug Evaluation, Preclinical , Half-Life , Humans , Mice , Microsomes/metabolism , Molecular Dynamics Simulation , Multiple Myeloma/drug therapy , Nuclear Proteins/metabolism , Protein Structure, Tertiary , Pyridones/pharmacokinetics , Pyridones/pharmacology , Pyridones/therapeutic use , Structure-Activity Relationship , Transcription Factors/metabolism , Transplantation, HeterologousABSTRACT
Curative interferon and ribavirin sparing treatments for hepatitis C virus (HCV)-infected patients require a combination of mechanistically orthogonal direct acting antivirals. A shared component of these treatments is usually an HCV NS5A inhibitor. First generation FDA approved treatments, including the component NS5A inhibitors, do not exhibit equivalent efficacy against HCV virus genotypes 1-6. In particular, these first generation NS5A inhibitors tend to select for viral drug resistance. Ombitasvir is a first generation HCV NS5A inhibitor included as a key component of Viekira Pak for the treatment of patients with HCV genotype 1 infection. Since the launch of next generation HCV treatments, functional cure for genotype 1-6 HCV infections has been achieved, as well as shortened treatment duration across a wider spectrum of genotypes. In this paper, we show how we have modified the anchor, linker, and end-cap architecture of our NS5A inhibitor design template to discover a next generation NS5A inhibitor pibrentasvir (ABT-530), which exhibits potent inhibition of the replication of wild-type genotype 1-6 HCV replicons, as well as improved activity against replicon variants demonstrating resistance against first generation NS5A inhibitors.
Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Drug Design , Hepacivirus/drug effects , Pyrrolidines/chemistry , Pyrrolidines/pharmacology , Animals , Antiviral Agents/pharmacokinetics , Benzimidazoles/pharmacokinetics , Genotype , Hepacivirus/genetics , Hepacivirus/physiology , Mice , Pyrrolidines/pharmacokinetics , Structure-Activity Relationship , Tissue Distribution , Virus Replication/drug effectsABSTRACT
ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection. This compound was identified during a medicinal chemistry effort to improve on an original lead, inhibitor 1, which we described in a previous publication. Replacement of the amide linkage in 1 with a trans-olefin resulted in improved compound permeability and solubility and provided much better pharmacokinetic properties in preclinical species. Replacement of the dihydrouracil in 1 with an N-linked uracil provided better potency in the genotype 1 replicon assay. Results from phase 1 clinical studies supported once-daily oral dosing with ABT-072 in HCV infected patients. A phase 2 clinical study that combined ABT-072 with the HCV protease inhibitor ABT-450 provided a sustained virologic response at 24 weeks after dosing (SVR24) in 10 of 11 patients who received treatment.
Subject(s)
Cytosine/analogs & derivatives , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Hepacivirus/enzymology , Stilbenes/chemistry , Sulfonamides/chemical synthesis , Sulfonamides/pharmacology , Viral Nonstructural Proteins/antagonists & inhibitors , Administration, Oral , Biological Availability , Chemistry Techniques, Synthetic , Cytosine/chemical synthesis , Cytosine/chemistry , Cytosine/pharmacokinetics , Cytosine/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacokinetics , Humans , Permeability , Stereoisomerism , Sulfonamides/chemistry , Sulfonamides/pharmacokinetics , Tissue Distribution , Viral Nonstructural Proteins/chemistryABSTRACT
Gd2O3-xSx:Er crystals were prepared through high-temperature solid-state reaction method in vacuum, with the vacuum synthesis mechanism determined by thermal analysis. The crystal structure and upconversion luminescence properties were investigated respectively by XRD, TEM and spectrophotometer. Well crystallized Gd2O2S:Er phosphors were prepared under 1000°C in vacuum with a certain excessive amount of sulfur content than stoichiometric. It is confirmed that with the increasing sulfur content the green emission was enhanced and red emission was weakened. The cooperative upconversion luminescence of Er3+ in non-stoichiometric Gd2O3-xSx crystals was interpreted as a result of two photon absorption and the photon avalanche process.
ABSTRACT
The development of bromodomain and extraterminal domain (BET) bromodomain inhibitors and their examination in clinical studies, particularly in oncology settings, has garnered substantial recent interest. An effort to generate novel BET bromodomain inhibitors with excellent potency and drug metabolism and pharmacokinetics (DMPK) properties was initiated based upon elaboration of a simple pyridone core. Efforts to develop a bidentate interaction with a critical asparagine residue resulted in the incorporation of a pyrrolopyridone core, which improved potency by 9-19-fold. Additional structure-activity relationship (SAR) efforts aimed both at increasing potency and improving pharmacokinetic properties led to the discovery of the clinical candidate 63 (ABBV-075/mivebresib), which demonstrates excellent potency in biochemical and cellular assays, advantageous exposures and half-life both in animal models and in humans, and in vivo efficacy in mouse models of cancer progression and inflammation.
Subject(s)
Drug Discovery , Proteins/antagonists & inhibitors , Pyridones/pharmacology , Sulfonamides/pharmacology , Animals , Cell Line, Tumor , Chromatography, High Pressure Liquid , Fluorescence Resonance Energy Transfer , Half-Life , Humans , Mass Spectrometry , Mice , Proton Magnetic Resonance Spectroscopy , Pyridones/chemistry , Pyridones/pharmacokinetics , Structure-Activity Relationship , Sulfonamides/chemistry , Sulfonamides/pharmacokineticsABSTRACT
Members of the BET family of bromodomain containing proteins have been identified as potential targets for blocking proliferation in a variety of cancer cell lines. A two-dimensional NMR fragment screen for binders to the bromodomains of BRD4 identified a phenylpyridazinone fragment with a weak binding affinity (1, Ki = 160 µM). SAR investigation of fragment 1, aided by X-ray structure-based design, enabled the synthesis of potent pyridone and macrocyclic pyridone inhibitors exhibiting single digit nanomolar potency in both biochemical and cell based assays. Advanced analogs in these series exhibited high oral exposures in rodent PK studies and demonstrated significant tumor growth inhibition efficacy in mouse flank xenograft models.
Subject(s)
Macrocyclic Compounds/chemistry , Macrocyclic Compounds/pharmacology , Pyridones/chemistry , Pyridones/pharmacology , Animals , Crystallography, X-Ray , Drug Discovery , Macrocyclic Compounds/pharmacokinetics , Molecular Structure , Pyridones/pharmacokinetics , Rats , Structure-Activity RelationshipABSTRACT
ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered phase I clinical trials. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models, representing a variety of hematologic malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G1 cell-cycle arrest without extensive apoptosis. In this study, we show that ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin lymphoma, and multiple myeloma cells. Apoptosis induced by ABBV-075 was mediated in part by modulation of the intrinsic apoptotic pathway, exhibiting synergy with the BCL-2 inhibitor venetoclax in preclinical models of AML. In germinal center diffuse large B-cell lymphoma, BCL-2 levels or venetoclax sensitivity predicted the apoptotic response to ABBV-075 treatment. In vivo combination studies uncovered surprising benefits of low doses of ABBV-075 coupled with bortezomib and azacitidine treatment, despite the lack of in vitro synergy between ABBV-075 and these agents. The in vitro/in vivo activities of ABBV-075 described here may serve as a useful reference to guide the development of ABBV-075 and other BET family inhibitors for cancer therapy. Cancer Res; 77(11); 2976-89. ©2017 AACR.
Subject(s)
Androgen Antagonists/therapeutic use , Pyridones/therapeutic use , Sulfonamides/therapeutic use , Androgen Antagonists/pharmacology , Apoptosis , Cell Line, Tumor , Drug Synergism , Humans , Pyridones/pharmacology , Sulfonamides/pharmacology , TransfectionABSTRACT
An NMR fragment screen for binders to the bromodomains of BRD4 identified 2-methyl-3-ketopyrroles 1 and 2. Elaboration of these fragments guided by structure-based design provided lead molecules with significant activity in a mouse tumor model. Further modifications to the methylpyrrole core provided compounds with improved properties and enhanced activity in a mouse model of multiple myeloma.
Subject(s)
Antineoplastic Agents/chemistry , Nuclear Proteins/antagonists & inhibitors , Pyrroles/chemistry , Transcription Factors/antagonists & inhibitors , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Binding Sites , Cell Line, Tumor , Cell Proliferation/drug effects , Crystallography, X-Ray , Drug Design , Half-Life , Humans , Mice , Molecular Dynamics Simulation , Multiple Myeloma/drug therapy , Nuclear Proteins/metabolism , Pyrroles/chemical synthesis , Pyrroles/pharmacokinetics , Pyrroles/therapeutic use , Structure-Activity Relationship , Transcription Factors/metabolism , Transplantation, HeterologousABSTRACT
As a novel red long afterglow phosphor, Si(4+) and Ti(4+) ion codoped Gd2O2S:Eu phosphor with spherical morphology, sub-micrometer size and narrow particle size distribution was synthesized by solid-state reaction in vacuum. The vacuum synthesis mechanism was determined by thermal analysis. The crystal structure, luminescence properties and mechanisms were investigated respectively by XRD, SEM and fluorescence spectrophotometer. The results show that well-crystallized Gd2O2S:Eu,Si,Ti phosphors are of hexagonal structure which is in agreement with the standard powder peak positions of Gd2O2S hexagonal phase. It displays pure red emission because of the strongest peaks at 627nm and 617nm which are attributed to energy transfer ((5)D0-(7)F2). There is a little blue shift of charge transfer excitation band in the excitation spectra between the bulk and sub-micrometer-sized samples, which may stem from size dependent shift and different lattice distortion in the position of the Eu(3+)-ligand electron transfer absorption/excitation band. To further study the influence of the impurities in Gd2O2S:Eu crystals on crystal growth, the simulated crystal face and its XRD patterns were illustrated. The preferred orientation of crystal growth changed from crystal face (101) to (100) thus to result in different luminescence mechanisms.
Subject(s)
Europium/chemistry , Gadolinium/chemistry , Luminescent Agents/chemistry , Silicon/chemistry , Titanium/chemistry , Cations/chemistry , Crystallization , Luminescence , Models, Molecular , Particle Size , VacuumABSTRACT
We describe here N-phenylpyrrolidine-based inhibitors of HCV NS5A with excellent potency, metabolic stability, and pharmacokinetics. Compounds with 2S,5S stereochemistry at the pyrrolidine ring provided improved genotype 1 (GT1) potency compared to the 2R,5R analogues. Furthermore, the attachment of substituents at the 4-position of the central N-phenyl group resulted in compounds with improved potency. Substitution with tert-butyl, as in compound 38 (ABT-267), provided compounds with low-picomolar EC50 values and superior pharmacokinetics. It was discovered that compound 38 was a pan-genotypic HCV inhibitor, with an EC50 range of 1.7-19.3 pM against GT1a, -1b, -2a, -2b, -3a, -4a, and -5a and 366 pM against GT6a. Compound 38 decreased HCV RNA up to 3.10 log10 IU/mL during 3-day monotherapy in treatment-naive HCV GT1-infected subjects and is currently in phase 3 clinical trials in combination with an NS3 protease inhibitor with ritonavir (r) (ABT-450/r) and an NS5B non-nucleoside polymerase inhibitor (ABT-333), with and without ribavirin.
Subject(s)
Anilides/pharmacology , Antiviral Agents/pharmacology , Carbamates/pharmacology , Genotype , Hepacivirus/drug effects , Sulfonamides/pharmacology , Uracil/analogs & derivatives , Viral Nonstructural Proteins/antagonists & inhibitors , 2-Naphthylamine , Anilides/chemistry , Anilides/pharmacokinetics , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacokinetics , Biological Availability , Carbamates/chemistry , Carbamates/pharmacokinetics , Cell Line , Drug Discovery , Hepacivirus/enzymology , Humans , Proline , Rats , Sulfonamides/chemistry , Sulfonamides/pharmacokinetics , Uracil/chemistry , Uracil/pharmacokinetics , Uracil/pharmacology , ValineABSTRACT
The synthesis and structure-activity relationships of a novel aryl uracil series which contains a fused 5,6-bicyclic ring unit for HCV NS5B inhibition is described. Several analogs display replicon cell culture potencies in the low nanomolar range along with excellent rat pharmacokinetic values.
Subject(s)
Bridged Bicyclo Compounds/chemistry , Bridged Bicyclo Compounds/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Uracil/antagonists & inhibitors , Viral Nonstructural Proteins/antagonists & inhibitors , Animals , Bridged Bicyclo Compounds/chemical synthesis , Bridged Bicyclo Compounds/pharmacokinetics , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacokinetics , Hepacivirus/enzymology , RNA-Dependent RNA Polymerase/antagonists & inhibitors , RNA-Dependent RNA Polymerase/metabolism , Rats , Structure-Activity Relationship , Uracil/pharmacology , Viral Nonstructural Proteins/metabolismABSTRACT
Efforts to improve the genotype 1a potency and pharmacokinetics of earlier naphthyridine-based HCV NS5A inhibitors resulted in the discovery of a novel series of pyrido[2,3-d]pyrimidine compounds, which displayed potent inhibition of HCV genotypes 1a and 1b in the replicon assay. SAR in this system revealed that the introduction of amides bearing an additional 'E' ring provided compounds with improved potency and pharmacokinetics. Introduction of a chiral center on the amide portion resulted in the observation of a stereochemical dependence for replicon potency and provided a site for the attachment of functional groups useful for improving the solubility of the series. Compound 21 was selected for administration in an HCV-infected chimpanzee. Observation of a robust viral load decline provided positive proof of concept for inhibition of HCV replication in vivo for the compound series.
Subject(s)
Pyrimidines/chemistry , Pyrimidines/pharmacology , Viral Nonstructural Proteins/antagonists & inhibitors , Drug Discovery , Humans , Structure-Activity Relationship , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/metabolismABSTRACT
The synthesis of several pyrido[2,3-d]pyrimidine and pyrimido[4,5-d]pyrimidine analogs is described with one such analog possessing subnanomolar potency in both genotype 1a and 1b cell culture HCV replicon assays.
Subject(s)
Antiviral Agents/chemical synthesis , Hepacivirus/drug effects , Pyrimidines/chemical synthesis , RNA, Viral/antagonists & inhibitors , Antiviral Agents/pharmacology , Cell Line, Tumor , Genotype , Hepacivirus/physiology , Humans , Pyrimidines/pharmacology , RNA, Viral/biosynthesis , Replicon/drug effects , Structure-Activity Relationship , Virus Replication/drug effectsABSTRACT
Silicon carbide nanowires have been synthesized at 1400 degrees C by carbothermic reduction of silica with bamboo carbon under normal atmosphere pressure without metallic catalyst. X-ray diffraction, scanning electron microscopy, energy-dispersive spectroscopy, transmission electron microscopy and Fourier transformed infrared spectroscopy were used to characterize the silicon carbide nanowires. The results show that the silicon carbide nanowires have a core-shell structure and grow along <111> direction. The diameter of silicon carbide nanowires is about 50-200 nm and the length from tens to hundreds of micrometers. The vapor-solid mechanism is proposed to elucidate the growth process. The photoluminescence of the synthesized silicon carbide nanowires shows significant blueshifts, which is resulted from the existence of oxygen defects in amorphous layer and the special rough core-shell interface.