CA224, a non-planar analogue of fascaplysin, inhibits Cdk4 but not Cdk2 and arrests cells at G0/G1 inhibiting pRB phosphorylation.


:Tryptamine derivatives, non-planar and potentially less toxic analogues of the anti-cancer agent fascaplysin, have been synthesised. They specifically inhibit Cdk4-D1 vis a vis Cdk2-A but, unlike fascaplysin, do not bind or intercalate DNA. CA224 is the most potent compound identified (Cdk4-D1 IC(50) approximately 5.5 microM). As would be expected of a Cdk4 inhibitor that does not inhibit Cdk2, it maintains a G(0)/G(1) block in synchronised cancer cells and inhibits Cdk4-specific phosphorylation of the retinoblastoma protein.


Bioorg Med Chem Lett


Mahale S,Aubry C,James Wilson A,Jenkins PR,Maréchal JD,Sutcliffe MJ,Chaudhuri B




Has Abstract


2006-08-15 00:00:00














  • Anti-HIV activity of stilbene-related heterocyclic compounds.

    abstract::Viral transcription has not been routinely targeted in the development of new antiviral drugs. This crucial step of the viral cycle depends on the concerted action of cellular and viral proteins such as NF-kappaB and Tat. In the present study, stilbene-related heterocyclic compounds including benzalphthalide, phthalaz...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Bedoya LM,del Olmo E,Sancho R,Barboza B,Beltrán M,García-Cadenas AE,Sánchez-Palomino S,López-Pérez JL,Muñoz E,San Feliciano A,Alcamí J

    更新日期:2006-08-01 00:00:00

  • Synthesis and biological evaluation of novel heterocyclic quinones as inhibitors of the dual specificity protein phosphatase CDC25C.

    abstract::A focused set of heterocyclic quinones based on the benzothiazole, benzoxazole, benzimidazole, indazole and isoindole was prepared and screened with respect to the inhibition of the phosphatase activity of CDC25C. Benzoxazole- and benzothiazole-diones were at least 50 times more potent in inhibiting CDC25C than their ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Lavergne O,Fernandes AC,Bréhu L,Sidhu A,Brézak MC,Prévost G,Ducommun B,Contour-Galcera MO

    更新日期:2006-01-01 00:00:00

  • Interaction between morphine and lysine.

    abstract::The study by the molecular orbital theory displayed that morphine and lysine make two types of the interactions between them: type (A) by three hydrogen bondings and type (B) by one hydrogen bonding accompanied with a proton transfer. The stabilization energies were 45.3 and 34.9 kcal/mol for type (A) and type (B), re...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Nakai S,Yoneda F

    更新日期:2001-06-04 00:00:00

  • Synthesis and preliminary investigations into novel 1,2,3-triazole-derived androgen receptor antagonists inspired by bicalutamide.

    abstract::A versatile and high yielding synthesis of novel androgen receptor (AR) antagonists is presented. Using this methodology, six 1,4-substituted-1,2,3-triazole derived bicalutamide mimics were synthesised in five steps and in isolated overall yields from 41% to 85%. Evaluation of these compounds for their anti-proliferat...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Altimari JM,Niranjan B,Risbridger GP,Schweiker SS,Lohning AE,Henderson LC

    更新日期:2014-11-01 00:00:00

  • Immunosuppressive effect of zhankuic acid C from Taiwanofungus camphoratus on dendritic cell activation and the contact hypersensitivity response.

    abstract::Some ergostane triterpenoids from Taiwanofungus camphoratus have been shown to exhibit anti-inflammatory activity in vitro. However, the effect of ergostane triterpenoids on the immune response remains unknown. In this study, we elucidated that ergostane triterpenoids significantly decreased the cytokines and chemokin...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Lin MK,Lee MS,Chang WT,Chen HY,Chen JF,Li YR,Lin CC,Wu TS

    更新日期:2015-10-15 00:00:00

  • Synthesis and antimicrobial activity of some new pyrazole derivatives containing a ferrocene unit.

    abstract::A series of new imines and amines have been synthesized by condensation of 1H-3-ferrocenyl-1-phenylpyrazole-4-carboxaldehyde with the corresponding amines, followed by reduction with sodium borohydride. The synthesized compounds have been screened for their in vitro antimicrobial activity against 11 bacteria and three...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Damljanović I,Vukićević M,Radulović N,Palić R,Ellmerer E,Ratković Z,Joksović MD,Vukićević RD

    更新日期:2009-02-15 00:00:00

  • Microwave-assisted synthesis of novel 5-substituted benzylidene amino-2-butyl benzofuran-3-yl-4-methoxyphenyl methanones as antileishmanial and antioxidant agents.

    abstract::A series of 5-substitutedbenzylideneamino-2-butylbenzofuran-3-yl-4-methoxyphenyl methanones is synthesized and evaluated for antileishmanial and antioxidant activities. Compounds 4f (IC50 = 52.0 ± 0.09 µg/ml), 4h (IC50 = 56.0 ± 0.71 µg/ml) and 4l (IC50 = 59.3 ± 0.55 µg/ml) were shown significant antileishmanial when c...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Patil SR,Bollikonda S,Patil RH,Sangshetti JN,Bobade AS,Asrondkar A,Reddy PP,Shinde DB

    更新日期:2018-02-01 00:00:00

  • Design and synthesis of functionalized piperazin-1yl-(E)-stilbenes as inhibitors of 17α-hydroxylase-C17,20-lyase (Cyp17).

    abstract::The synthesis of steroid hormones is critical to human physiology and improper regulation of either the synthesis of these key molecules or activation of the associated receptors can lead to disease states. This has led to intense interest in developing compounds capable of modulating the synthesis of steroid hormones...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Blass BE,Iyer P,Abou-Gharbia M,Childers WE,Gordon JC,Ramanjulu M,Morton G,Arumugam P,Boruwa J,Ellingboe J,Mitra S,Reddy Nimmareddy R,Paliwal S,Rajasekhar J,Shivakumar S,Srivastava P,Tangirala RS,Venkataramanaiah K,Bob

    更新日期:2018-07-15 00:00:00

  • Structure-activity relationships of adenosine A3 receptor ligands: new potential therapy for the treatment of glaucoma.

    abstract::Structure-activity relationships (SAR) of fused 1,2,4-triazolo[1,5-c ]pyrimidine were performed. Various substituents were introduced into the heterocyclic ring to improve the potency of adenosine A(3) receptor binding affinity and A(3)-selectivity against other subtypes. Potent and selective A(3) receptor antagonists...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Okamura T,Kurogi Y,Hashimoto K,Sato S,Nishikawa H,Kiryu K,Nagao Y

    更新日期:2004-07-16 00:00:00

  • Synthesis and antiplatelet effects of an isoxazole series of glycoprotein IIb/IIIa antagonists.

    abstract::Despite the excellent in vitro potency of a series of benzamide glycoprotein IIb/IIIa antagonists, which have been reported previously, poor in vivo potency in the inhibition of platelet aggregation was observed when the most potent inhibitor XU057 was dosed intravenously to dogs. In this communication, we report that...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Xue CB,Roderick J,Mousa S,Olson RE,DeGrado WF

    更新日期:1998-12-15 00:00:00

  • Synthesis, antimycobacterial and antibacterial activity of l-[(1R,2S)-2-fluorocyclopropyl]naphthyridone derivatives containing an oxime-functionalized pyrrolidine moiety.

    abstract::A series of novel 1-[(1R,2S)-2-fluorocyclopropyl]naphthyridone derivatives 21-24 containing an oxime-functionalized pyrrolidine moiety were designed, synthesized and evaluated for their biological activity. Our results reveal that compounds 21a, 21e and 21j show considerable activity against MTB H37Rv ATCC 27294 (MICs...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Huang J,Liu H,Liu M,Zhang R,Li L,Wang B,Wang M,Wang C,Lu Y

    更新日期:2015-11-15 00:00:00

  • Assessment of new 2'-O-acetalester protecting groups for regular RNA synthesis and original 2'-modified proRNA.

    abstract::New base-labile acyloxymethyl groups were evaluated to protect 2'-OH functions of ribonucleotides for regular RNA synthesis in order to shorten the deprotection procedure upon ammonia. These same acetalester groups were assessed in 2'-modified proRNA as biolabile 2'-protections removable by cell enzymes to generate pa...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Martin AR,Lavergne T,Vasseur JJ,Debart F

    更新日期:2009-08-01 00:00:00

  • Novel bis-arylsulfonamides and aryl sulfonimides as inactivators of plasminogen activator inhibitor-1 (PAI-1).

    abstract::Inactivators of plasminogen activator inhibitor-1 (PAI-1) have been identified as possible treatments for a range of conditions, including atherosclerosis, venous thrombosis, and obesity. We describe the synthesis and inhibitory activity of a novel series of compounds based on bis-arylsulfonamide and aryl sulfonimide ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: El-Ayache NC,Li SH,Warnock M,Lawrence DA,Emal CD

    更新日期:2010-02-01 00:00:00

  • Synthesis and structure-activity relationship of 3,4'-bispyridinylethylenes: discovery of a potent 3-isoquinolinylpyridine inhibitor of protein kinase B (PKB/Akt) for the treatment of cancer.

    abstract::Structure-based design and synthesis of the 3,4'-bispyridinylethylene series led to the discovery of 3-isoquinolinylpyridine 13a as a potent PKB/Akt inhibitor with an IC(50) of 1.3nM against Akt1. Compound 13a shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Li Q,Woods KW,Thomas S,Zhu GD,Packard G,Fisher J,Li T,Gong J,Dinges J,Song X,Abrams J,Luo Y,Johnson EF,Shi Y,Liu X,Klinghofer V,Des Jong R,Oltersdorf T,Stoll VS,Jakob CG,Rosenberg SH,Giranda VL

    更新日期:2006-04-01 00:00:00

  • New photocleavable linker: α-thioacetophenone-type linker.

    abstract::Photocleavable linkers are advantageous over the common linkers because they could be cleaved without using reagents. A novel photocleavable linker with an α-thioacetophenone moiety has been developed. This linker, which can be cleaved upon irradiation at 365 nm via the Norrish type II reaction, is applicable to a pro...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Yonezawa H,Nishiyama Y,Takeo K,Iwatsubo T,Tomita T,Yokoshima S,Fukuyama T

    更新日期:2014-07-01 00:00:00

  • Farnesyl protein transferase inhibitors targeting the catalytic zinc for enhanced binding.

    abstract::Successful efforts to make farnesyl transferase (FT) inhibitors with appropriately tethered ligands designed to interact with a catalytic zinc that exist in the enzyme have been realized. Thus, by introducing either a pyridylmethylamino or propylaminolimidazole amide moieties off the 2-position of the piperidine ring,...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Njoroge FG,Vibulbhan B,Pinto P,Strickland C,Kirschmeier P,Bishop WR,Girijavallabhan V

    更新日期:2004-12-06 00:00:00

  • Synthesis and biological evaluation of novel (L)-alpha-amino acid methyl ester, heteroalkyl, and aryl substituted 1,4-naphthoquinone derivatives as antifungal and antibacterial agents.

    abstract::A series of (S)-N-(1,4-naphthoquinon-2-yl)-alpha-amino acid methyl esters 3-9, 2-N,N-dialkylamino-1,4-naphthoquinones 10-11 and 2-hydroxy-3-(2'-mercaptoimidazolyl)-1,4-naphthoquinones and their cyclic analogs 12-15 were synthesized and evaluated for antifungal and antibacterial activities. The structure-activity relat...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Tandon VK,Yadav DB,Singh RV,Chaturvedi AK,Shukla PK

    更新日期:2005-12-01 00:00:00

  • The purine transferase from Trypanosoma cruzi as a potential target for bisphosphonate-based chemotherapeutic compounds.

    abstract::We identified and tested bisphosphonates as inhibitors of a protozoan molecular target. Computational modeling studies demonstrated that these compounds are mimics of the natural substrate of the enzyme. The most potent bisphosphonates in vitro are pamidronate and risedronate, which inhibit the purine transferase from...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Fernández D,Wenck MA,Craig SP 3rd,Delfino JM

    更新日期:2004-09-06 00:00:00

  • Synthesis and biological evaluation of novel carbazole-rhodanine conjugates as topoisomerase II inhibitors.

    abstract::In this study, a series of carbazole-rhodanine conjugates was synthesized and evaluated for their Topoisomerase II inhibition potency as well as cytotoxicity against a panel of four human cancer cell lines. Among these thirteen compounds, 3a, 3b, 3g, and 3h possessed Topoisomerase II inhibition potency at 20 μM. Mecha...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Jiang H,Zhang WJ,Li PH,Wang J,Dong CZ,Zhang K,Chen HX,Du ZY

    更新日期:2018-05-01 00:00:00

  • Design, synthesis and biological evaluation of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates as potential photodynamic therapeutical agents.

    abstract::5-Aminolaevulinic acid (ALA) prodrugs have been widely used in photodynamic therapy (PDT) as precursors to the natural photosensitizer, protoporphyrin IX (PpIX). The main disadvantage of this therapy is that ALA is poorly absorbed by cells due to its high hydrophilicity. In order to improve the therapeutical effect an...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Zhu CF,Battah S,Kong X,Reeder BJ,Hider RC,Zhou T

    更新日期:2015-02-01 00:00:00

  • Facile and efficient one-pot synthesis of 4beta-arylaminopodophyllotoxins: synthesis of DNA topoisomerase II inhibitors (NPF and W-68).

    abstract::A series of 4beta-arylamino-4'-O-demethylepipodophyllotoxins and 4beta-arylaminoepipodophyllotoxins have been synthesized with significant stereoselectivity and improved yields by employing the methanesulphonic acid/sodium iodide reagent system. Compounds NPF. W-68 and other DNA topoisomerase II inhibitors are prepare...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kamal A,Laxman N,Ramesh G

    更新日期:2000-09-18 00:00:00

  • New highly selective inhibitors of class II fructose-1,6-bisphosphate aldolases.

    abstract::Phosphoglycolo amidoxime and phosphoglycolo hydrazide, two new derivatives of phosphoglycolic acid, were synthesised and successfully tested as selective competitive inhibitors of class II FBP-aldolases. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Fonvielle M,Weber P,Dabkowska K,Therisod M

    更新日期:2004-06-07 00:00:00

  • Using enzymatic amplification by aldolase for the optical detection of DNA by an artificial signal cascade.

    abstract::A two-step reaction cascade is applied to the sequence-specific detection of single-stranded DNA, including analyte-triggered re-activation of apo-aldolase by its cofactor Zn(2+) and catalytic conversion of a chromophore. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Graf N,Kassube S,Krämer R

    更新日期:2008-09-01 00:00:00

  • Discovery of highly selective CRAF inhibitors, 3-carboxamido-2H-indazole-6-arylamide: In silico FBLD design, synthesis and evaluation.

    abstract::The recent success of vemurafenib shows the importance of selective BRAF V600E inhibition in melanoma. However, paradoxical activation by structurally diverse ATP-competitive RAF kinase inhibitors strongly suggests that selective CRAF inhibitors, not BRAF inhibitors, would be ideal for some Ras mutation cancer treatme...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Aman W,Lee J,Kim M,Yang S,Jung H,Hah JM

    更新日期:2016-02-15 00:00:00

  • Study on antitumor activities of the chrysin-chromene-spirooxindole on Lewis lung carcinoma C57BL/6 mice in vivo.

    abstract::The our previous study synthesized the chrysin-chromene-spirooxindole hybrids 3, and further found compound 3e had good antitumor activity against A549 cells in vitro through multi-target co-regulation of the p53 signalling pathway to inhibit the proliferation of A549 cells. This study was designed to evaluate the ant...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Zhang WH,Chen S,Liu XL,Bing-Lin,Liu XW,Zhou Y

    更新日期:2020-09-01 00:00:00

  • New merosesquiterpenes from a Vietnamese marine sponge of Spongia sp. and their biological activities.

    abstract::The investigation of the Vietnamese marine sponge Spongia sp. led to the isolation of three new sesquiterpene phenols, langconols A-C (1-3), and one new sesquiterpene hydroxyquinone, langcoquinone C (4), together with two known meroterpenoids (5 and 6). Their structures were determined on the basis of spectroscopic an...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Nguyen HM,Ito T,Kurimoto SI,Ogawa M,Win NN,Hung VQ,Nguyen HT,Kubota T,Kobayashi J,Morita H

    更新日期:2017-07-15 00:00:00

  • Structure-activity relationships of trans-substituted-propenoic acid derivatives on the nicotinic acid receptor HCA2 (GPR109A).

    abstract::Nicotinic acid (niacin) has been used for decades as an antidyslipidemic drug in man. Its main target is the hydroxy-carboxylic acid receptor HCA2 (GPR109A), a G protein-coupled receptor. Other acids and esters such as methyl fumarate also interact with the receptor, which constituted the basis for the current study. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: van Veldhoven JP,Blad CC,Artsen CM,Klopman C,Wolfram DR,Abdelkadir MJ,Lane JR,Brussee J,Ijzerman AP

    更新日期:2011-05-01 00:00:00

  • Design, synthesis and enzymatic evaluation of 3-O-substituted aryl β-D-galactopyranosides as inhibitors of Trypanosoma cruzi trans-sialidase.

    abstract::The trans-sialidase of Trypanosoma cruzi (TcTS) is a surface enzyme that modifies the parasite glycocalyx covering it with sialic acid. This process is essential to adhesion and invasion mechanisms in life cycle of the protozoan in the human host, making TcTS a very attractive molecular target for drug design. Using t...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Silva BL,S Filho JD,Andrade P,Carvalho I,Alves RJ

    更新日期:2014-09-15 00:00:00

  • Optimization of imidazole amide derivatives as cannabinoid-1 receptor antagonists for the treatment of obesity.

    abstract::Several imidazole-based cyclohexyl amides were identified as potent CB-1 antagonists, but they exhibited poor oral exposure in rodents. Incorporation of a hydroxyl moiety on the cyclohexyl ring provided a dramatic improvement in oral exposure, together with a ca. 10-fold decrease in potency. Further optimization provi...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Smith RA,Fathi Z,Achebe F,Akuche C,Brown SE,Choi S,Fan J,Jenkins S,Kluender HC,Konkar A,Lavoie R,Mays R,Natoli J,O'Connor SJ,Ortiz AA,Su N,Taing C,Tomlinson S,Tritto T,Wang G,Wirtz SN,Wong W,Yang XF,Ying S,

    更新日期:2007-05-15 00:00:00

  • Effect of linker substitution on the binding of butorphan univalent and bivalent ligands to opioid receptors.

    abstract::A series of bivalent hydroxy ether butorphan ligands were prepared and their binding affinities at the opioid receptors determined. Addition of a hydroxy group to a hydrocarbon chain can potentiate binding affinity up to 27- and 86-fold at the mu and kappa opioid receptors, respectively. Two bivalent ligands with sub-...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Fulton BS,Knapp BL,Bidlack JM,Neumeyer JL

    更新日期:2010-03-01 00:00:00