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1.
J Burn Care Res ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32147708

RESUMO

Wound infection is a serious complication in burnt injury, which is a common form of trauma and an important public health issue. We investigated samples from burn and non-burn wounds for microbial characteristics and temporal trends of antibiotic resistance. Wound samples were collected from 369 burnt patients and 927 non-burnt individuals admitted from 2007 to 2017. Higher frequency of A. baumannii, K. pneumonia and P. aeruginosa were observed in samples from burnt individuals when compared to those from non-burnt patients. The prevalence of different groups of bacteria varied when the samples were stratified according to age and sex. The antimicrobial resistance profiles showed significant difference between burnt and non-burnt patients. The different temporal trends of antimicrobial resistance rates were also found, which may be critical for proper selection of antibiotics in burn treatment. The present study suggested that frequent pathogens and antibacterial resistance evolution could differ between burn wounds and other wounds. Therefore, periodic surveillance of antibiotic resistance patterns in burn unit might help physicians properly select of antibiotics for treatment.

3.
4.
Acta Pharmacol Sin ; 41(2): 270-277, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31316177

RESUMO

KRAS is one of the most important proto-oncogenes. Its mutations occur in almost all tumor types, and KRAS mutant cancer is still lack of effective therapy. Prenyl-binding protein phosphodiesterase-δ (PDEδ) is required for the plasma membrane association and subsequent activation of KRAS oncogenic signaling. Recently, targeting PDEδ has provided new promise for KRAS mutant tumors. However, the therapeutic potential of PDEδ inhibition remains obscure. In this study, we explored how PDEδ inhibition was responded in KRAS mutant cancer cells, and identified KRAS mutant subset responsive to PDEδ inhibition. We first performed siRNA screen of KRAS growth dependency of a small panel of human cancer lines, and identified a subset of KRAS mutant cancer cells that were highly dependent on KRAS signaling. Among these cells, only a fraction of KRAS-dependent cells responded to PDEδ depletion, though KRAS plasma membrane association was effectively impaired. We revealed that the persistent RAF/MEK/ERK signaling seemed responsible for the lack of response to PDEδ depletion. A kinase array further identified that the feedback activation of EPH receptor A2 (EPHA2) accounted for the compensatory activation of RAF/MEK/ERK signaling in these cells. Simultaneous inhibition of EPHA2 and PDEδ led to the growth inhibition of KRAS mutant cancer cells. Together, this study gains a better understanding of PDEδ-targeted therapeutic strategy and suggests the combined inhibition of EPHA2 and PDEδ as a potential therapy for KRAS mutant cancer.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31828667

RESUMO

BACKGROUND AND OBJECTIVE: Dan-Hong injection, which comprises extracts of Salvia miltiorrhiza and Carthamus tinctorius, promotes blood circulation and reduces blood stasis. Combination of S. miltiorrhiza and C. tinctorius is more effective in treating cerebral ischemia than S. miltiorrhiza alone. This study aimed to examine the pharmacokinetic characteristics of four active ingredients of S. miltiorrhiza and C. tinctorius, namely danshensu (DSS), hydroxysafflor yellow A (HSYA), and salvianolic acid A (SAA) and B (SAB) in normal and cerebral ischemia rats. METHODS: Normal and cerebral ischemia rats were injected via the tail vein with each active ingredient, and blood was collected through the jaw vein at different time points. The plasma concentration of the compatibility group was analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using Pharmacokinetic Kinetica 4.4 software. RESULTS: The pharmacokinetics of the four active ingredients in the normal and cerebral ischemia rats were consistent with a two-compartment model. The area under the concentration-time curve was higher in normal rats than in cerebral ischemia rats, with a highly significant difference for SAA (P < 0.01). Clearance rates were lower in normal rats than in cerebral ischemia rats, with DSS showing the most significant difference (P < 0.01). Furthermore, there were significant differences between normal and cerebral ischemia rats in the distribution phase-elimination half life for DSS, SAA, and HSYA, as well as in the apparent volume of distribution for the central compartment for DSS and HSYA (P < 0.01). The plasma concentrations of the four active ingredients were higher in normal rats than in cerebral ischemia rats. CONCLUSION: Cerebral ischemia rats showed higher drug clearance rates and longer retention times than normal rats, which may be due to destruction of the blood-brain barrier during cerebral ischemia-reperfusion. The four active ingredients likely integrated and interacted with each other to affect target sites in the brain to protect against cerebral ischemic injury.

6.
BMC Musculoskelet Disord ; 20(1): 632, 2019 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-31884960

RESUMO

BACKGROUND: Although the risk factors associated with osteonecrosis of femoral head (ONFH) after internal fixation of femoral neck fracture (IFFNF) have been frequently reported, the results remain controversial. Therefore, its related risk factors were systematically evaluated and meta-classified in this study. METHODS: Literature on risk factors of ONFH caused by IFFNF was retrieved in PubMed, Embase and Cochrane Library due June 2019. Review Manager 5.3 software was applied to data synthesis, and Stata 13.0 software was adopted for analyses of publication bias and sensitivity. RESULTS: A total of 17 case-control studies with 2065 patients were included. The risk of ONFH after IF was 0.40-fold higher in patients with Garden III-IV FNF than that in patients with Garden I-II (OR: 0.40, 95%CI: 0.29-0.55). The risk of OFNH with retained IF was uplifted by 0.04 times (OR: 0.04, 95%CI: 0.02-0.07). There was nonsignificant relationship between gender and ONFH after IFFNF (OR: 1.27, 95%CI: 0.84-1.94). Moreover, ONFH after IFFNF presented no association with age (OR:1.66, 95%CI: 0.89-3.11), injury-operation interval (OR:1.29, 95%CI: 0.82-2.04), fracture reduction mode (OR:1.98, 95%CI: 0.92-4.26), preoperative traction (OR:1.69, 95%CI: 0.29-9.98) and mechanism of injury (OR:0.53, 95%CI: 0.06-4.83). Egger's and Begg's tests indicated a publication bias (P = 0.001). CONCLUSION: It was demonstrated that Garden classification and retained IF were important influencing factors of ONFH after IFFNF. Gender, age, injury-operation interval, fracture reduction mode, preoperative traction and the mechanism of ONFH were irrelevant to the complication.

7.
Medicine (Baltimore) ; 98(43): e17648, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651886

RESUMO

BACKGROUND: Vascular dementia (VaD) is the second prevalent dementia worldwide attributable to cognitive impairments. Acupuncture has been applied in clinic as a therapeutic modality to treat VaD. This systematic review and meta-analysis aims to evaluate current evidence to explore the effectiveness and safety of acupuncture treatment to cognitive impairment of VaD. METHODS: Randomized controlled trials will be searched restricted to their inception from January 1, 2000 to September 15, 2019. The following literature databases will be searched, including 4 English databases: PubMed, Excerpta Medica Database, the Cochrane Library, Medline, and 4 Chinese databases, namely the China National Knowledge Infrastructure Database, the Wanfang Database, the Chinese Scientific Journal Database, and the Chinese BioMedical Literature Database. After the selection and extraction of eligible studies, a meta-analysis will be undertaken to assess the efficacy and safety of acupuncture on VaD. The Review Manager Software V.5.3.5 will be employed for meta-analysis to assess the risk of bias, data synthesis, and subgroup analysis. RESULTS: The systematic review and meta-analysis will be carried out to evaluate the efficacy and safety of acupuncture in the treatment of VaD, further provide an evidence-based synthesis for clinical and research applications. CONCLUSIONS: The summary of our systematic review will determine whether acupuncture intervention to VaD is safe and well-tolerated in global status.


Assuntos
Terapia por Acupuntura/métodos , Disfunção Cognitiva/terapia , Demência Vascular/terapia , Humanos , Metanálise como Assunto , Projetos de Pesquisa , Revisão Sistemática como Assunto
8.
Biochem Biophys Res Commun ; 519(2): 246-252, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31495492

RESUMO

BACKGROUND: Bladder cancer (BCa) is one of the most common urological malignancies. While Inositol-3-phosphate synthase 1 (ISYNA1) expression and function were largely unknown in BCa. We aimed to study the expression and role of ISYNA1 in bladder cancer and investigate its potential mechanisms via ingenuity pathway analysis (IPA). METHODS: ISYNA1 expression was quantified by qRT-PCR in bladder cancer cell lines as well as normal urothelial cell line. Knocking down ISYNA1 gene in BCa T24 cells was achieved by shRNA lentivirus transfection. MTT and Celigo assay were used to assess cell proliferation. Flow cytometry was applied to test cell cycle and apoptosis. In addition, IPA was performed using PrimeView™ Human Gene Expression Array. Imunohistochemistry (IHC) was performed in BCa patient tissue microarray to verify the association between ISYNA1 expression and patients' clinicopathological features. RESULTS: ISYNA1 was significantly upregulated in BCa samples vs. para-tumor tissues. Higher expression were significantly associated with tumor T stage and lymph node metastasis of bladder cancer patients. Similarly, it was elevated in BCa cell lines (5637 and T24) compared with SVHUC cells. Knocking down ISYNA1 significantly decreased proliferation, induced apoptosis and cell cycle arrest in T24 cells. Furthermore, IPA indicated that ISYNA1 was an important regulatory factors and related networks were involved in multiple functional processes. CONCLUSION: Taken together, current study suggest ISYNA1 promotes proliferation and inhibit apoptosis in bladder cancer cells, and its expression correlated with BCa patients' clinicopathological features. Thus, ISYNA1 may serve as a potential biomarker and therapeutic target for BCa patients.

9.
J Med Chem ; 62(18): 8642-8663, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31490070

RESUMO

BRD4 has recently emerged as a promising drug target. Therefore, identifying novel inhibitors with distinct properties could enrich their use in anticancer treatment. Guided by the cocrystal structure of hit compound 4 harboring a five-membered-ring linker motif, we quickly identified lead compound 7, which exhibited good antitumor effects in an MM.1S xenograft model by oral administration. Encouraged by its high potency and interesting scaffold, we performed further lead optimization to generate a novel potent series of bromodomain and extra-terminal (BET) inhibitors with a (1,2,4-triazol-5-yl)-3,4-dihydroquinoxalin-2(1H)-one structure. Among them, compound 19 was found to have the best balance of activity, stability, and antitumor efficacy. After confirming its low brain penetration, we conducted comprehensive preclinical studies, including a multiple-species pharmacokinetics profile, extensive cellular mechanism studies, hERG assay, and in vivo antitumor growth effect testing, and we found that compound 19 is a potential BET protein drug candidate for the treatment of cancer.

10.
Adv Mater ; : e1903407, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31486182

RESUMO

III-nitride semiconductors have attracted considerable attention in recent years owing to their excellent physical properties and wide applications in solid-state lighting, flat-panel displays, and solar energy and power electronics. Generally, GaN-based devices are heteroepitaxially grown on c-plane sapphire, Si (111), or 6H-SiC substrates. However, it is very difficult to release the GaN-based films from such single-crystalline substrates and transfer them onto other foreign substrates. Consequently, it is difficult to meet the ever-increasing demand for wearable and foldable applications. On the other hand, sp2 -bonded two-dimensional (2D) materials, which exhibit hexagonal in-plane lattice arrangements and weakly bonded layers, can be transferred onto flexible substrates with ease. Hence, flexible III-nitride devices can be implemented through such 2D release layers. In this progress report, the recent advances in the different strategies for the growth of III-nitrides based on 2D materials are reviewed, with a focus on van der Waals epitaxy and transfer printing. Various attempts are presented and discussed herein, including the different kinds of 2D materials (graphene, hexagonal boron nitride, and transition metal dichalcogenides) used as release layers. Finally, current challenges and future perspectives regarding the development of flexible III-nitride devices are discussed.

11.
Invest New Drugs ; 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31267379

RESUMO

The bromodomain and extra-terminal domain (BET) family of proteins, especially bromodomain-containing protein 4 (BRD4), has emerged as exciting anti-tumor targets due to their important roles in epigenetic regulation. Therefore, the discovery of BET inhibitors with promising anti-tumor efficacy will provide a novel approach to epigenetic anticancer therapy. Recently, we discovered the new BET inhibitor compound 171, which is derived from a polo-like kinase 1 (PLK1)-BRD4 dual inhibitor based on our previous research. Compound 171 was found to maintain BET inhibition ability without PLK1 inhibition, and there was no selectivity among BET family members. The in vitro and in vivo results both indicated that the overall anti-tumor activity of compound 171 was improved compared with the (+)-JQ-1 or OTX-015 BET inhibitors. Furthermore, we found that compound 171 could regulate the expression of cell cycle-regulating proteins including c-Myc and p21 and induce cell cycle arrest in the G0/G1 phase. However, compound 171 only has a quite limited effect on apoptosis, in considering that apoptosis was only observed at doses greater than 50 µM. To determine the mechanisms underlying cell death, proliferation activity assay was conducted. The results showed that compound 171 induced clear anti-proliferative effects at doses that no obvious apoptosis was induced, which indicated that the cell cycle arresting effect contributed mostly to its anti-tumor activity. The result of this study revealed the anti-tumor mechanism of compound 171, and laid a foundation for the combination therapy in clinical practice, if compound 171 or its series compounds become drug candidates in the future.

12.
Cell Death Dis ; 10(8): 557, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324754

RESUMO

The bromodomain and extra terminal domain (BET) family members, including BRD2, BRD3, and BRD4, act as epigenetic readers to regulate gene expression. Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that participates in tumor immune escape primarily by catalyzing tryptophan to L-kynurenine. Here, we report that IDO1 is a new target gene of the BET family. RNA profiling showed that compound 9, a new BET inhibitor, reduced IDO1 mRNA up to seven times in Ty-82 cells. IDO1 differentially expressed in tumor cells and its expression could be induced with interferon gamma (IFN-γ). BET inhibitors (ABBV-075, JQ1, and OTX015) inhibited both constitutive and IFN-γ-inducible expression of IDO1. Similarly, reduction of BRD2, BRD3, or BRD4 decreased IDO1 expression. All these BET family members bound to the IDO1 promoter via the acetylated histone H3. JQ1 led to their release and reduced enrichment of RNA polymerase II (Pol II) on the promoter. IFN-γ increased the binding of BRD2, BRD3, BRD4, and Pol II on the IDO1 promoter by increasing the acetylation of histone H3, which could be prevented by JQ1 partially or even completely. Furthermore, both JQ1 and OTX015 decreased the production of L-kynurenine. The combination of BET inhibitors with the IDO1 inhibitor further reduced L-kynurenine, though only marginally. Importantly, the BET inhibitor ABBV-075 significantly inhibited the growth of human Ty-82 xenografts in nude mice and reduced both protein and mRNA levels of IDO1 in the xenografts. This finding lays a basis for the potential combination of BET inhibitors and IDO1 inhibitors for the treatment of IDO1-expressing cancers.

13.
Appl Opt ; 58(13): 3555-3563, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31044854

RESUMO

We propose a novel approach to laser frequency noise characterization by delayed self-heterodyne. Compared with the traditional treatment, our method applies to both long and short delay, corresponding to uncorrelated and correlated self-heterodyne. In the case of long delay, it overcomes the influence of 1/f noise on the intrinsic linewidth extraction from a broadened spectrum, and the results are more accurate than Voigt profile fitting. For short delayed correlated heterodyne, it eliminates artifact peaks at multiples of the reciprocal of delay time introduced by transferring measured RF phase noise to laser phase noise, thus extending the measurement range. In addition, it calibrates the frequency noise overestimation caused by a finite noise floor. This method remains valid when the delay and the coherence time are comparable. Experimental results are presented to demonstrate the effectiveness of the proposed approach in characterizing lasers with intrinsic linewidth ranging from sub-100 Hz to megahertz.

14.
J Med Chem ; 62(11): 5414-5433, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31117515

RESUMO

PRMT4 is a type I protein arginine methyltransferase and plays important roles in various cellular processes. Overexpression of PRMT4 has been found to be involved in several types of cancers. Selective and in vivo effective PRMT4 inhibitors are needed for demonstrating PRMT4 as a promising therapeutic target. On the basis of compound 6, a weak dual PRMT4/6 inhibitor, we constructed a tetrahydroisoquinoline scaffold through a cut-and-sew scaffold hopping strategy. The subsequent SAR optimization efforts employed structure-based approach led to the identification of a novel PRMT4 inhibitor 49. Compound 49 exhibited prominently high potency and selectivity, moderate pharmacokinetic profiles, and good antitumor efficacy in acute myeloid leukemia xenograft model via oral administration, thus demonstrating this compound as a useful pharmacological tool for further target validation and drug development in cancer therapy.

15.
Acta Pharm Sin B ; 9(2): 351-368, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30972282

RESUMO

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with in vitro metabolic stability tests and in vivo pharmacokinetic profiling, a representative compound (35) was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor 35 was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.

16.
Bioorg Med Chem Lett ; 29(6): 844-847, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30713023

RESUMO

Tranylcypromine moiety extracted from LSD1 inhibitors and 6-trifluoroethyl thienopyrimidine moiety from menin-MLL1 PPI inhibitors were merged to give new chemotypes for medicinal chemistry study. Among 15 new compounds prepared in this work, some exhibited nanomolar LSD1 activity and good selectivity over MAO-A/B, low micromolar menin-MLL1 PPI inhibitory activity, as well as submicromolar MV4-11 antiprofilative activities. Intracellular LSD1 engagement of compounds with higher enzymatic and antiproliferative activities was confirmed by CD86 mRNA up-regulation experiments.


Assuntos
Antineoplásicos/farmacologia , Histona Desmetilases/antagonistas & inibidores , Inibidores da Monoaminoxidase/farmacologia , Pirimidinas/farmacologia , Tranilcipromina/farmacologia , Antineoplásicos/síntese química , Antígeno B7-2/genética , Linhagem Celular Tumoral , Humanos , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/síntese química , Pirimidinas/síntese química , RNA Mensageiro/metabolismo , Tiofenos/síntese química , Tiofenos/farmacologia , Tranilcipromina/análogos & derivados , Tranilcipromina/síntese química , Regulação para Cima/efeitos dos fármacos
17.
J Cell Physiol ; 234(8): 13592-13601, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30609030

RESUMO

Bladder cancer (BCa) is one of the most prevalent cancers of the urinary system worldwide. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) perform a vital function in the pathogenesis and progression of BCa. In the current study, we identified a novel lncRNA OXCT1-AS1 and investigated its role and potential mechanisms in BCa. The microarray results showed the expression of lncRNAs, microRNAs, and messenger RNAs between BCa primary tumor tissues and metastatic lymph nodes were significantly different. The quantitative polymerase chain reaction verification was performed to ensure the reliability of the screening results. The Cell Counting Kit 8 and transwell assay were used to assess the tumor cell proliferation and invasion abilities in vitro, respectively. The dual-luciferase activity assay was performed to investigate the potential mechanism of competing endogenous RNA network. lncRNA OXCT1-AS1, which elevated in metastasis lymph node, was significantly upregulated in BCa cell lines compared with SVHUC-1. We demonstrated OXCT1-AS1 inhibited miR-455-5p to decrease its binding to the JAK1 3'-untranslated region, which could upregulate the expression of JAK1 at the protein level, thus promoting BCa proliferation and invasion. Therefore, lncRNA OXCT1-AS1 could act as a potential biomarker and therapeutic target for patients with BCa.

18.
Eur J Med Chem ; 163: 597-609, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30562696

RESUMO

Although mutated Ras protein is well recognized as an important drug target, direct targeting Ras has proven to be a daunting task. Recent studies demonstrated that Ras protein needs PDEδ to relocate to plasma membrane to execute its signaling transduction function, which provides a new avenue for modulating the Ras protein. To find small molecules antagonizing the interactions between PDEδ and Ras, here we presented a successful application of fragment-based drug discovery of PDEδ inhibitors. Under the guidance of crystal structures, we are able to quickly optimize the initial fragment into highly potent inhibitors, with more than 2000-fold improvement in binding activity, which further adds to the arsenal towards the inhibition of Ras signaling in cancer therapy.


Assuntos
Descoberta de Drogas , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/metabolismo , Ligação Proteica/efeitos dos fármacos , Triazóis/uso terapêutico , Proteínas ras/metabolismo , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Triazóis/farmacologia
19.
ACS Appl Mater Interfaces ; 11(1): 1228-1238, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30521305

RESUMO

Stranski-Krastanov (SK) growth mode is widely adopted for the self-assembled growth of semiconductor quantum dots (QDs), wherein a relatively large critical thickness is essential and a thick wetting layer (WL) is formed beneath the QD layer. In this paper, we report the metal organic vapor phase epitaxy of green InGaN QDs, employing a growth interruption method to decrease the critical thickness and improve the morphology of QDs. The QDs exhibit similar photoluminescence properties with those grown by conventional SK mode, implying the existence of a WL. We experimentally verify that the formation of QDs, whether based on the SK mode or the growth interruption method, conforms to the phase separation theory. However, the density of QDs grown by the interruption method exhibits abnormal dependence on the strain when a quantum well (QW) is inserted beneath the QD layer. Furthermore, the underlying QW not only influences the morphology of the QDs but also plays as a reservoir of electrons, which helps enhance the photoluminescence and the electroluminescence of the QDs. The method of QD growth with improved morphology and luminescence by introducing the QW-QD coupled nanostructure is universally applicable to similar material systems. Furthermore, a 550 nm green light-emitting diode (LED) and a 526 nm superluminescent LED based on the nanostructure are demonstrated.

20.
Eur J Med Chem ; 163: 671-689, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30572178

RESUMO

Although lung adenocarcinoma patients have benefited from the development of targeted therapy, patients with lung squamous cell carcinoma (SqCC) have no effective treatment due to the complexity and heterogeneity of the disease. Therefore, basing on the genetic analysis of mutations in lung squamous cell carcinoma to design multi-target inhibitors represents a potential strategy for the medical treatment. In this study, through screening an in-house focused library, we identified an interesting indazole scaffold. And following with binding analysis, we elaborated the structure-activity relationship of this hit compound by optimizing four parts guided by the DDR2 enzymatic assay, which resulted in a potent lead compound 10a. We conducted further optimization of dual enzymatic inhibitions towards FGFR1 and DDR2, two important kinases in lung squamous cell carcinoma. Finally, from the cellular antiproliferative activity tests and in vivo pharmacokinetic test, 3-substituted indazole derivative 11k was found to be a promising candidate and subjected to in vivo pharmacology study with the mouse xenograft models, demonstrating profound anti-tumor efficacy. Additional in vitro druglike assessment reinforced that compound 11k could be valuable for SqCC drug development.


Assuntos
Antineoplásicos/síntese química , Carcinoma de Células Escamosas/tratamento farmacológico , Descoberta de Drogas , Indazóis/síntese química , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/química , Animais , Carcinoma de Células Escamosas/enzimologia , Receptor com Domínio Discoidina 2/antagonistas & inibidores , Xenoenxertos , Humanos , Indazóis/química , Indazóis/farmacologia , Neoplasias Pulmonares/enzimologia , Camundongos , Inibidores de Proteínas Quinases/uso terapêutico , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Relação Estrutura-Atividade
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