Amgen - c-Met

Design, Synthesis, and Biological Evaluation of Potent c-Met Inhibitors. D'Angelo ND, Bellon SF, Booker SK, Cheng Y, Coxon A, Dominguez C, Fellows I, Hoffman D, Hungate R, Kaplan-Lefko P, Lee MR, Li C, Liu L, Rainbeau E, Reider PJ, Rex K, Siegmund A, Sun Y, Tasker AS, Xi N, Xu S, Yang Y, Zhang Y, Burgess TL, Dussault I, Kim TS.

BMS - IGF-1R

Discovery and Evaluation of 4-(2-(4-chloro-1H-pyrazol-1-yl)ethylamino)-3-(6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one (BMS-695735), an Orally Efficacious Inhibitor of Insulin-like Growth Factor-1 Receptor Kinase with Broad Spectrum in Vivo Antitumor Activity. Velaparthi U, Wittman M, Liu P, Carboni JM, Lee FY, Attar R, Balimane P, Clarke W, Sinz MW, Hurlburt W, Patel K, Discenza L, Kim S, Gottardis M, Greer A, Li A, Saulnier M, Yang Z, Zimmermann K, Trainor G, Vyas D.

H-bond Analysis - Astellas

Identification of a key element for hydrogen-bonding patterns between protein kinases and their inhibitors. Katayama N, Orita M, Yamaguchi T, Hisamichi H, Kuromitsu S, Kurihara H, Sakashita H, Matsumoto Y, Fujita S, Niimi T.

Patent Publications - 09/04/2008

US20080214567
Benzimidazole Thiophene Compounds

US20080214563
Benzimidazole Thiophene Compounds As Plk Modulators

PKA/Akt - Abbott

Syntheses of potent, selective, and orally bioavailable indazole-pyridine series of protein kinase B/Akt inhibitors with reduced hypotension.
LinksZhu GD, Gandhi VB, Gong J, Thomas S, Woods KW, Song X, Li T, Diebold RB, Luo Y, Liu X, Guan R, Klinghofer V, Johnson EF, Bouska J, Olson A, Marsh KC, Stoll VS, Mamo M, Polakowski J, Campbell TJ, Martin RL, Gintant GA, Penning TD, Li Q, Rosenberg SH, Giranda VL.

p38 - BMS

Structural basis for the high-affinity binding of pyrrolotriazine inhibitors of p38 MAP kinase.
LinksSack JS, Kish KF, Pokross M, Xie D, Duke GJ, Tredup JA, Kiefer SE, Newitt JA.

IRAK4 - UCB

IRAK-4 inhibitors. Part III: a series of imidazo[1,2-a]pyridines. Buckley GM, Fosbeary R, Fraser JL, Gowers L, Higueruelo AP, James LA, Jenkins K, Mack SR, Morgan T, Parry DM, Pitt WR, Rausch O, Richard MD, Sabin V.

TrkA - Cephalon

TrkA kinase inhibitors from a library of modified and isosteric Staurosporine aglycone. Tripathy R, Angeles TS, Yang SX, Mallamo JP.

Src - University of Rhode Island

Development of Src tyrosine kinase substrate binding site inhibitors. Ye G, Tiwari R, Parang K.

p38 - Eberhard-Karls-University Tuebingen

Design, synthesis, and biological evaluation of novel Tri- and tetrasubstituted imidazoles as highly potent and specific ATP-mimetic inhibitors of p38 MAP kinase: focus on optimized interactions with the enzyme's surface-exposed front region. Laufer SA, Hauser DR, Domeyer DM, Kinkel K, Liedtke AJ.

JAK2 - University of Florida

Z3, a novel Jak2 tyrosine kinase small-molecule inhibitor that suppresses Jak2-mediated pathologic cell growth. Sayyah J, Magis A, Ostrov DA, Allan RW, Braylan RC, Sayeski PP.

JNK - Pfizer

Pharmacological characterization of a small-molecule inhibitor of c-Jun kinase. Cho HK, Black SC, Looper D, Shi M, Kelly-Sullivan D, Timofeevski S, Siegel K, McDonnell SR, Yu XH, Chen P, Yie J, Ogilvie KM, Fraser JD, Briscoe CP.

PI3K - Piramed/Genentech

The Identification of 2-(1H-Indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a Potent, Selective, Orally Bioavailable Inhibitor of Class I PI3 Kinase for the Treatment of Cancer. Folkes AJ, Ahmadi K, Alderton WK, Alix S, Baker SJ, Box G, Chuckowree IS, Clarke PA, Depledge P, Eccles SA, Friedman LS, Hayes A, Hancox TC, Kugendradas A, Lensun L, Moore P, Olivero AG, Pang J, Patel S, Pergl-Wilson GH, Raynaud FI, Robson A, Saghir N, Salphati L, Sohal S, Ultsch MH, Valenti M, Wallweber HJ, Wan NC, Wiesmann C, Workman P, Zhyvoloup A, Zvelebil MJ, Shuttleworth SJ.

PDB Update 08/29/08

Ceska, T.A.
Achieving multi-isoform PI3K inhibition in a series of substituted 3,4-Dihydro-2H-benzo[1,4]oxazines
Resolution: 2.85 Å

Clinical Trial Results of Nilotinib

Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL.
Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG.

Clinical Trial Results of Sunitinib

Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial.
Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG.


Sunitinib in patients with metastatic renal cell carcinoma.
Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR, Redman BG, Margolin KA, Merchan JR, Wilding G, Ginsberg MS, Bacik J, Kim ST, Baum CM, Michaelson MD.

Clinical Trial Results of Lapatinib

Lapatinib plus capecitabine for HER2-positive advanced breast cancer.
Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D.

Clinical Trial Results of Ruboxistaurin

A 6-month, randomized, double-masked, placebo-controlled study evaluating the effects of the protein kinase C-beta inhibitor ruboxistaurin on skin microvascular blood flow and other measures of diabetic peripheral neuropathy.
Casellini CM, Barlow PM, Rice AL, Casey M, Simmons K, Pittenger G, Bastyr EJ 3rd, Wolka AM, Vinik AI.

Clinical Trial Results of CEP-1347

Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease.
Parkinson Study Group PRECEPT Investigators.

Clinical Trial Results of Axitinib

Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study.
Spano JP, Chodkiewicz C, Maurel J, Wong R, Wasan H, Barone C, Létourneau R, Bajetta E, Pithavala Y, Bycott P, Trask P, Liau K, Ricart AD, Kim S, Rixe O.

Clinical Trial Results of Dasatinib

Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia.
Shah NP, Kantarjian HM, Kim DW, Réa D, Dorlhiac-Llacer PE, Milone JH, Vela-Ojeda J, Silver RT, Khoury HJ, Charbonnier A, Khoroshko N, Paquette RL, Deininger M, Collins RH, Otero I, Hughes T, Bleickardt E, Strauss L, Francis S, Hochhaus A.

Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia.
Porkka K, Koskenvesa P, Lundán T, Rimpiläinen J, Mustjoki S, Smykla R, Wild R, Luo R, Arnan M, Brethon B, Eccersley L, Hjorth-Hansen H, Höglund M, Klamova H, Knutsen H, Parikh S, Raffoux E, Gruber F, Brito-Babapulle F, Dombret H, Duarte RF, Elonen E, Paquette R, Zwaan CM, Lee FY.

Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias.
Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R, Cortes J, O'Brien S, Nicaise C, Bleickardt E, Blackwood-Chirchir MA, Iyer V, Chen TT, Huang F, Decillis AP, Sawyers CL.

Clinical Trial Results of Motesanib

Motesanib diphosphate in progressive differentiated thyroid cancer.
Sherman SI, Wirth LJ, Droz JP, Hofmann M, Bastholt L, Martins RG, Licitra L, Eschenberg MJ, Sun YN, Juan T, Stepan DE, Schlumberger MJ; Motesanib Thyroid Cancer Study Group.

Clinical Trial Results of Sorafenib

Sorafenib in advanced hepatocellular carcinoma.
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group.

Sorafenib in advanced clear-cell renal-cell carcinoma.
Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group.

PDB Update 08/26/08

Abad, M.C.
Structure of EGFR in complex with hydrazone, a potent dual inhibitor
Resolution: 2.00 Å

Pike, A.C.W., Rellos, P., King, O., Salah, E., Parizotto, E., Fedorov, O., Shrestha, L., Burgess-Brown, N., Roos, A., Murray, J.W., Von Delft, F., Edwards, A., Arrowsmith, C.H., Wikstroem, M., Bountra, C., Knapp, S.
STRUCTURE OF HUMAN CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE TYPE II ALPHA (CAMK2A) IN COMPLEX WITH INDIRUBIN E804
Resolution: 2.30 Å

Sack, J.
Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor C-MET in complex with a Pyrrolopyridinepyridone based inhibitor
Resolution: 2.40 Å

Elling, R.A., Baskaran, S., Allen, D.A., Oslob, J.D., Romanowski, M.J.
Crystal structure of mouse Aurora A (Asn186->Gly, Lys240->Arg, Met302->Leu) in complex with 1-{5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)-ethyl]- thiazol-2-yl}-3-(3-trifluoromethyl-phenyl)-urea
Resolution: 1.90 Å

B-Raf - Furans- GSK

The identification of potent, selective and CNS penetrant furan-based inhibitors of B-Raf kinase. Takle AK, Bamford MJ, Davies S, Davis RP, Dean DK, Gaiba A, Irving EA, King FD, Naylor A, Parr CA, Ray AM, Reith AD, Smith BB, Staton PC, Steadman JG, Stean TO, Wilson DM.

PDK1 Modeling - University of Kentucky

Combined 3D-QSAR Modeling and Molecular Docking Study on Indolinone Derivatives as Inhibitors of 3-Phosphoinositide-Dependent Protein Kinase-1. Abdulhameed MD, Hamza A, Liu J, Zhan CG.

Selectivity Prediction - Pfizer

Predicting Kinase Selectivity Profiles Using Free-Wilson QSAR Analysis. Sciabola S, Stanton RV, Wittkopp S, Wildman S, Moshinsky D, Potluri S, Xi H.

Patent Applications - 08/22/2008

US20080200496
SUBSTITUTED 1H-PYRROLO[3,2-b, 3,2-c, and 2,3-c]PYRIDINE-2-CARBOXAMIDES AND RELATED ANALOGS AS INHIBITORS OF CASEIN KINASE Ie The present invention discloses and claims compounds of formula (I) wherein M is N, and K and L are each C with the remaining substituents further defined herein. These compounds are effective...

US20080200486
Combination Of Organic Compounds The invention provides a pharmaceutical combination comprising: a) a pyrimidylaminobenzamide compound, and b) an mTOR kinase inhibitor and a method for treating or preventing a...

US20080200485
Kinase Inhibitors Disclosed are protein kinase inhibitors, compositions comprising such inhibitors, and methods of use, thereof. More particularly, disclosed are inhibitors of Aurora-2 (Aurora-A) protein kinase....

US20080199426
Methods and compositions for the treatment and diagnosis of vascular inflammatory disorders or endothelial cell disorders Disclosed herein are methods for treating a vascular inflammatory disorder or endothelial cell disorder using inhibitor compounds that inhibit the expression or biological activity of Tie-1, Tie-1...

US20080200509
3,4-DISUBSTITUTED 1H-PYRAZOLE COMPOUNDS AND THEIR USE AS CYCLIN DEPENDENT KINASE AND GLYCOGEN SYNTHASE KINASE-3 MODULATORS The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof for use in the prophylaxis or treatment of disease states and conditions such as cancers...

PDB Update 08/21/08

3D4Q
Pyrazole-based inhibitors of B-Raf kinase
Resolution: 2.80 Å

3DB6
Crystal structure of an activated (Thr->Asp) Polo-like kinase 1 (Plk1) catalytic domain in complex with Compound 902
Resolution: 2.85 Å

3DCV
Crystal structure of human Pim1 kinase complexed with 4-(4-hydroxy-3-methyl-phenyl)-6-phenylpyrimidin-2(1H)-one
Resolution: 2.70 Å

Review of Computational Methods - Cephalon

Knowledge Based Prediction of Ligand Binding Modes and Rational Inhibitor Design for Kinase Drug Discovery. Ghose AK, Herbertz T, Pippin DA, Salvino JM, Mallamo JP.

Lck - University of Pittsburgh

Small molecule inhibitors of Lck: the search for specificity within a kinase family. Meyn MA 3rd, Smithgall TE.

Angiokinase - Boehringer Ingelheim

BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ.