当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > (Bis)urea and (bis)thiourea inhibitors of lysine-specific demethylase 1 as epigenetic modulators.

(Bis)urea and (bis)thiourea inhibitors of lysine-specific demethylase 1 as epigenetic modulators.

Abstract：

:The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 overexpression is thought to contribute to the development of cancer. We recently reported a series of (bis)guanidines and (bis)biguanides that are potent inhibitors of LSD1 and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of isosteric ureas and thioureas that are also potent inhibitors of LSD1. These compounds induce increases in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2 and transcription factor GATA4. These compounds represent an important new series of epigenetic modulators with the potential for use as antitumor agents.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Sharma SK,Wu Y,Steinbergs N,Crowley ML,Hanson AS,Casero RA,Woster PM

doi

10.1021/jm100217a

subject

Has Abstract

pub_date

2010-07-22 00:00:00

pages

5197-212

issue

14

eissn

0022-2623

issn

1520-4804

journal_volume

53

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Design and synthesis of pyrrolidine-5,5-trans-lactams (5-oxo-hexahydro-pyrrolo[3,2-b]pyrroles) as novel mechanism-based inhibitors of human cytomegalovirus protease. 1. The alpha-methyl-trans-lactam template.

    abstract：:Mechanism-based inhibitors of human cytomegalovirus (HCMV) protease have been designed based on the pyrrolidine-5,5-trans-lactam ring system. New routes to the beta-methyl-, desmethyl-, and alpha-methyl-pyrrolidine-5,5-trans-lactam templates have been developed from 2,4-diaminobutyric acid. ESI/MS studies have shown t...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm000078q

    authors： Borthwick AD,Angier SJ,Crame AJ,Exall AM,Haley TM,Hart GJ,Mason AM,Pennell AM,Weingarten GG

    更新日期：2000-11-16 00:00:00

  • Synthesis and biological evaluation of fatty acyl ester derivatives of (-)-2',3'-dideoxy-3'-thiacytidine.

    abstract：:A number of fatty acyl derivatives of (-)-2',3'-dideoxy-3'-thiacytidine (lamivudine, 3TC, 1) were synthesized and evaluated for their anti-HIV activity. The monosubstituted 5'-O-fatty acyl derivatives of 3TC (EC(50) = 0.2-2.3 μM) were more potent than the corresponding monosubstituted N(4)-fatty acyl (EC(50) = 0.4-29....

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm300492q

    authors： Agarwal HK,Chhikara BS,Hanley MJ,Ye G,Doncel GF,Parang K

    更新日期：2012-05-24 00:00:00

  • Synthesis and in Vivo Evaluation of [123I]Melanin-Targeted Agents.

    abstract：:This study reports the synthesis, [(123)I]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [(131)I]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60-90% r...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b00777

    authors： Roberts MP,Nguyen V,Ashford ME,Berghofer P,Wyatt NA,Krause-Heuer AM,Pham TQ,Taylor SR,Hogan L,Jiang CD,Fraser BH,Lengkeek NA,Matesic L,Gregoire MC,Denoyer D,Hicks RJ,Katsifis A,Greguric I

    更新日期：2015-08-13 00:00:00

  • Mono- and bis(aminomethyl)phenylacetic acid esters as short-acting antiarrhythmic agents. 2.

    abstract：:The synthesis, antiarrhythmic activity, and blood hydrolysis properties of a series of mono- and bis(aminomethyl)phenylacetic acid esters related to a previously reported class Ic antiarrhythmic agent (ACC-9358) are described. Of the various oxa-, aza-, thia-, and carbacyclic esters initially prepared in the bis(pyrro...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00069a007

    authors： Chorvat RJ,Black LA,Ranade VV,Barcelon-Yang C,Stout DM,Brown BS,Stampfli HF,Quon CY

    更新日期：1993-08-20 00:00:00

  • Compass: predicting biological activities from molecular surface properties. Performance comparisons on a steroid benchmark.

    abstract：:We describe a new method, Compass, for predicting the biological activities of molecules based on the activities and three-dimensional structures of other molecules. The method improves on previous techniques by representing only the surface of molecules, by incorporating a nonlinear statistical method, and by automat...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00041a010

    authors： Jain AN,Koile K,Chapman D

    更新日期：1994-07-22 00:00:00

  • The identification of perillyl alcohol glycosides with improved antiproliferative activity.

    abstract：:A facile route to perillyl alcohol (POH) differential glycosylation and the corresponding synthesis of a set of 34 POH glycosides is reported. Subsequent in vitro studies revealed a sugar dependent antiproliferative activity and the inhibition of S6 ribosomal protein phosphorylation as a putative mechanism of represen...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm500870u

    authors： Nandurkar NS,Zhang J,Ye Q,Ponomareva LV,She QB,Thorson JS

    更新日期：2014-09-11 00:00:00

  • (E)-3-(4-Oxo-4H-quinazolin-3-yl)-2-propenoic acids, a new series of antiallergy agents.

    abstract：:A series of substituted (E)-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acids was prepared and evaluated in the rat passive cutaneous anaphylaxis (PCA) test for antiallergic activity. Alkoxy, alkylthio, and isopropyl substituents at the 6- or 8-positions provided highly potent compounds. Conversion to the Z isomer, reduc...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00357a018

    authors： LeMahieu RA,Carson M,Nason WC,Parrish DR,Welton AF,Baruth HW,Yaremko B

    更新日期：1983-03-01 00:00:00

  • Reactions of artemisinin and arteether with acid: implications for stability and mode of antimalarial action.

    abstract：:The currently accepted mechanism of trioxane antimalarial action involves generation of free radicals within or near susceptible sites probably arising from the production of distonic radical anions. An alternative mechanistic proposal involving the ionic scission of the peroxide group and consequent generation of a c...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060673d

    authors： Drew MG,Metcalfe J,Dascombe MJ,Ismail FM

    更新日期：2006-10-05 00:00:00

  • Affinity of 2-(tetrahydroisoquinolin-2-ylmethyl)- and 2-(isoindolin-2-ylmethyl)imidazolines for alpha-adrenoceptors. Differential affinity of imidazolines for the [3H]idazoxan-labeled alpha 2-adrenoceptor vs the [3H]yohimbine-labeled site.

    abstract：:A series of 2-(tetrahydroisoquinolin-2-ylmethyl)- and 2-(isoindolin-2-ylmethyl)imidazolines were prepared and tested for alpha 1- and alpha 2-adrenoceptor affinity with radioligand binding. Several compounds, 5-fluoro-(5h), 5-chloro-(5j), 5,8-dimethoxy- (5r), and 5,8-dimethoxy- (5r),1-methyl- (5s) 2-(tetrahydroisoquin...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00164a021

    authors： Clark RD,Berger J,Garg P,Weinhardt KK,Spedding M,Kilpatrick AT,Brown CM,MacKinnon AC

    更新日期：1990-02-01 00:00:00

  • Glucosamine-glycerophospholipids that activate cell-matrix adhesion and migration.

    abstract：:Two new analogues derived from the platelet activating factor (PAF), containing glucosamine instead of the acetyl group, were synthesized, and their effect on the human keratinocyte cell line HaCaT was evaluated with respect to cytotoxicity, proliferation, adhesion, and migration. Starting with (R)-1,2-isopropylideneg...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm050558n

    authors： Bartolmäs T,Heyn T,Mickeleit M,Fischer A,Reutter W,Danker K

    更新日期：2005-10-20 00:00:00

  • Synthesis of new acridone derivatives, inhibitors of NS3 helicase, which efficiently and specifically inhibit subgenomic HCV replication.

    abstract：:A new goup of acridone derivatives, obtained by reaction of acridone-4-carboxylic acid derivatives with aromatic amines, was tested to determine the inhibitory properties toward the NS3 helicase of hepatitis C virus (HCV). Six compounds inhibited the NS3 helicase at low concentrations (IC(50) from 1.5 to 20 microM). T...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm901741p

    authors： Stankiewicz-Drogoń A,Dörner B,Erker T,Boguszewska-Chachulska AM

    更新日期：2010-04-22 00:00:00

  • The discovery and characterization of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor potentiator N-{(3S,4S)-4-[4-(5-cyano-2-thienyl)phenoxy]tetrahydrofuran-3-yl}propane-2-sulfonamide (PF-04958242).

    abstract：:A unique tetrahydrofuran ether class of highly potent α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor potentiators has been identified using rational and structure-based drug design. An acyclic lead compound, containing an ether-linked isopropylsulfonamide and biphenyl group, was pharmacologically augmen...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b00300

    authors： Shaffer CL,Patel NC,Schwarz J,Scialis RJ,Wei Y,Hou XJ,Xie L,Karki K,Bryce DK,Osgood SM,Hoffmann WE,Lazzaro JT,Chang C,McGinnis DF,Lotarski SM,Liu J,Obach RS,Weber ML,Chen L,Zasadny KR,Seymour PA,Schmidt CJ,Haj

    更新日期：2015-05-28 00:00:00

  • 5-Lipoxygenase inhibitors: synthesis and structure-activity relationships of a series of 1-aryl-2H,4H-tetrahydro-1,2,4-triazin-3-ones.

    abstract：:Synthetic routes were developed to access a variety of novel 1-aryl-2H,4H-tetrahydro-1,2,4-triazin-3-one analogs which were evaluated as 5-lipoxygenase (5-LO) inhibitors. The parent structure, 1-phenylperhydro-1,2,4-triazin-3-one (4), was found to be a selective inhibitor of 5-LO in broken cell, intact cell, and human...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm960372b

    authors： Bhatia PA,Brooks CD,Basha A,Ratajczyk JD,Gunn BP,Bouska JB,Lanni C,Young PR,Bell RL,Carter GW

    更新日期：1996-09-27 00:00:00

  • Discovery of Hydrolysis-Resistant Isoindoline N-Acyl Amino Acid Analogues that Stimulate Mitochondrial Respiration.

    abstract：:N-Acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. We found that administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure, indicating that this pathway might be useful for treating obesity and associated...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b00029

    authors： Lin H,Long JZ,Roche AM,Svensson KJ,Dou FY,Chang MR,Strutzenberg T,Ruiz C,Cameron MD,Novick SJ,Berdan CA,Louie SM,Nomura DK,Spiegelman BM,Griffin PR,Kamenecka TM

    更新日期：2018-04-12 00:00:00

  • Synthesis, conformation, and immunosuppressive activities of three analogues of cyclosporin A modified in the 1-position.

    abstract：:The syntheses of three new cyclosporin A (CsA) analogues that contain novel MeBmt derivatives in the 1-position are described. The MeBmt analogue that contains an additional methyl group on C4, (2S,3R,6E)-4,4-dimethyl-3-hydroxy-2-(N-methylamino)-6-octenoic acid (MeBm2t), was synthesized in four steps beginning with th...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00165a018

    authors： Aebi JD,Deyo DT,Sun CQ,Guillaume D,Dunlap B,Rich DH

    更新日期：1990-03-01 00:00:00

  • Synthesis and benzodiazepine receptor affinities of rigid analogues of 3-carboxy-beta-carbolines: demonstration that the benzodiazepine receptor recognizes preferentially the s-cis conformation of the 3-carboxy group.

    abstract：:1H-Indolo[3',2':4,5]pyrido[3,2-b]-2-penten-5-olide (6) and 1H,5H-indolo[3',2'-c]-6,7-dihydro-2-pyridone (7), rigid analogues of methyl 4-ethyl-beta-carboline-3-carboxylate (8) and N-methyl-4-ethyl-beta-carboline-3-carboxamide (9), respectively, were synthesized and their in vitro binding affinities to the central type...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00128a023

    authors： Dorey G,Poissonnet G,Potier MC,Prado de Carvalho L,Venault P,Chapouthier G,Rossier J,Potier P,Dodd RH

    更新日期：1989-08-01 00:00:00

  • Resorcinol congeners of dopamine derived from benzocycloheptene and indan.

    abstract：:Series of N-alkylated derivatives of 2-amino-4,6-dihydroxyindan 3 and 6-amino-1,3-dihydroxybenzocycloheptene 2 were prepared for pharmacological testing as congeners of 2-amino-5,7-dihydroxytetralin, which elicits dopaminergic effects in a variety of assays. All of the subject compounds demonstrated a lower order of d...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00368a014

    authors： Cannon JG,Pease JP,Hamer RL,Ilhan M,Bhatnagar RK,Long JP

    更新日期：1984-02-01 00:00:00

  • Corticotropin-releasing hormone receptor antagonists: framework design and synthesis guided by ligand conformational studies.

    abstract：:As described in the preceding paper (Arvanitis et al. J. Med. Chem. 1999, 42), anilinopyrimidines I were identified as potent antagonists of corticotropin-releasing hormone-1 receptor (CRH1-R, also referred to as corticotropin-releasing factor, CRF1-R). Our next goal was to understand the receptor-bound conformation o...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm980223o

    authors： Hodge CN,Aldrich PE,Wasserman ZR,Fernandez CH,Nemeth GA,Arvanitis A,Cheeseman RS,Chorvat RJ,Ciganek E,Christos TE,Gilligan PJ,Krenitsky P,Scholfield E,Strucely P

    更新日期：1999-03-11 00:00:00

  • Design and synthesis of potent inhibitors of the malaria parasite dihydroorotate dehydrogenase.

    abstract：:Pyrimidine biosynthesis presents an attractive drug target in malaria parasites due to the absence of a pyrimidine salvage pathway. A set of compounds designed to inhibit the Plasmodium falciparum pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (PfDHODH) was synthesized. PfDHODH-specific inhibitors with lo...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060687j

    authors： Heikkilä T,Ramsey C,Davies M,Galtier C,Stead AM,Johnson AP,Fishwick CW,Boa AN,McConkey GA

    更新日期：2007-01-25 00:00:00

  • Chemical synthesis and biological activities of 5-deazaaminopterin analogues bearing substituent(s) at the 5- and/or 7-position(s).

    abstract：:Condensation of cyanothioacetamide (4) with ethyl alpha-(ethoxymethylene)acetoacetate (5b), ethyl 4-ethoxy-2-(ethoxymethylene)-3-oxobutanoate (5c), ethyl 2-(ethoxymethylene)-3-oxo-4-phenylpropanoate (5d) afforded exclusively the corresponding 6-substituted pyridines (6b-d). Cyclization of 4 with 3-carbethoxybutane-2,4...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00401a023

    authors： Su TL,Huang JT,Chou TC,Otter GM,Sirotnak FM,Watanabe KA

    更新日期：1988-06-01 00:00:00

  • Oral absorption of cephalosporin antibiotics. 3. Synthesis and biological properties of 7 alpha-methoxy-7 beta-(arylacetamido)-3-chloro-3-cephem-4- carboxylic acids.

    abstract：:A series of 7 alpha-methoxy-7 beta-amido-3-chloro-3-cephem-4-carboxylic acids was prepared and evaluated for biological activity. When compared with the parent 7-non-methoxy analogues, these new 7 alpha-methoxy-3-chloro cephalosporins displayed diminished antimicrobial activity. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00118a024

    authors： Pfeil-Doyle J,Kukolja S

    更新日期：1988-10-01 00:00:00

  • Antitumor agents. 280. Multidrug resistance-selective desmosdumotin B analogues.

    abstract：:6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR-selective flavonoid with significant in vitro anticancer activity against a multidrug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2 analogues were synthesized and evaluated to determine the effect of B-ring ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100846r

    authors： Nakagawa-Goto K,Chang PC,Lai CY,Hung HY,Chen TH,Wu PC,Zhu H,Sedykh A,Bastow KF,Lee KH

    更新日期：2010-09-23 00:00:00

  • Influence of glutathione on the oxidation of 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline: chemistry of potential relevance to the addictive and neurodegenerative consequences of ethanol use.

    abstract：:Recent evidence suggests that intraneuronal metabolism of ethanol by catalase/H2O2 and an ethanol-inducible form of cytochrome P450 together generate acetaldehyde and oxygen radicals including the hydroxyl radical (HO.). Within the cytoplasm of serotonergic neurons, these metabolic processes would thus provide acetald...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9504870

    authors： Han QP,Dryhurst G

    更新日期：1996-03-29 00:00:00

  • Design and Optimization of Sulfone Pyrrolidine Sulfonamide Antagonists of Transient Receptor Potential Vanilloid-4 with in Vivo Activity in a Pulmonary Edema Model.

    abstract：:Pulmonary edema is a common ailment of heart failure patients and has remained an unmet medical need due to dose-limiting side effects associated with current treatments. Preclinical studies in rodents have suggested that inhibition of transient receptor potential vanilloid-4 (TRPV4) cation channels may offer an alter...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b01344

    authors： Pero JE,Matthews JM,Behm DJ,Brnardic EJ,Brooks C,Budzik BW,Costell MH,Donatelli CA,Eisennagel SH,Erhard K,Fischer MC,Holt DA,Jolivette LJ,Li H,Li P,McAtee JJ,McCleland BW,Pendrak I,Posobiec LM,Rivera KLK,Rivero RA

    更新日期：2018-12-27 00:00:00

  • Discovery of novel 2-aryl-4-benzoyl-imidazoles targeting the colchicines binding site in tubulin as potential anticancer agents.

    abstract：:A series of 2-aryl-4-benzoyl-imidazoles (ABI) was synthesized as a result of structural modifications based on the previous set of 2-aryl-imidazole-4-carboxylic amide (AICA) derivatives and 4-substituted methoxylbenzoyl-aryl-thiazoles (SMART). The average IC(50) of the most active compound (5da) was 15.7 nM. ABI analo...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100884b

    authors： Chen J,Wang Z,Li CM,Lu Y,Vaddady PK,Meibohm B,Dalton JT,Miller DD,Li W

    更新日期：2010-10-28 00:00:00

  • Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors.

    abstract：:The development of pharmacotherapeutic treatments of psychostimulant abuse has remained a challenge, despite significant efforts made toward relevant mechanistic targets, such as the dopamine transporter (DAT). The atypical DAT inhibitors have received attention due to their promising pharmacological profiles in anima...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b01373

    authors： Cao J,Slack RD,Bakare OM,Burzynski C,Rais R,Slusher BS,Kopajtic T,Bonifazi A,Ellenberger MP,Yano H,He Y,Bi GH,Xi ZX,Loland CJ,Newman AH

    更新日期：2016-12-08 00:00:00

  • Polymethine Thiopyrylium Fluorophores with Absorption beyond 1000 nm for Biological Imaging in the Second Near-Infrared Subwindow.

    abstract：:Small-molecule fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window has gained increasing interest in clinical application. Till now, very few studies have been exploited in the small-molecule fluorophores with both excitation and emission in the NIR-II window. Inspired by the indocyanine gre...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b01682

    authors： Ding B,Xiao Y,Zhou H,Zhang X,Qu C,Xu F,Deng Z,Cheng Z,Hong X

    更新日期：2019-02-28 00:00:00

  • Whole structure-activity relationships of the fat-accumulation inhibitor (-)-ternatin: recognition of the importance of each amino acid residue.

    abstract：:A series of Ala and Aoc analogues of (-)-ternatin were prepared, and their bioactivities were assessed by a fat-accumulation inhibition assay using 3T3-L1 adipocytes, which led to the discovery of key structure-activity relationships (SAR). ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm800741n

    authors： Shimokawa K,Iwase Y,Miwa R,Yamada K,Uemura D

    更新日期：2008-10-09 00:00:00

  • Free energy component analysis for drug design: a case study of HIV-1 protease-inhibitor binding.

    abstract：:A theoretically rigorous and computationally tractable methodology for the prediction of the free energies of binding of protein-ligand complexes is presented. The method formulated involves developing molecular dynamics trajectories of the enzyme, the inhibitor, and the complex, followed by a free energy component an...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm010175z

    authors： Kalra P,Reddy TV,Jayaram B

    更新日期：2001-12-06 00:00:00

  • Small Molecule Inhibitor that Stabilizes the Autoinhibited Conformation of the Oncogenic Tyrosine Phosphatase SHP2.

    abstract：:Genetic mutations in the phosphatase PTPN11 (SHP2) are associated with childhood leukemias. These mutations cause hyperactivation of SHP2 due to the disruption of the autoinhibitory conformation. By targeting the activation-associated protein conformational change, we have identified an SHP2 inhibitor ( E)-1-(1-(5-(3-...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b00513

    authors： Wu X,Xu G,Li X,Xu W,Li Q,Liu W,Kirby KA,Loh ML,Li J,Sarafianos SG,Qu CK

    更新日期：2019-02-14 00:00:00