Hierarchic Informational Technology for Effective Molecular Design of Drug AgentsFrom Science to Business Workshop11-12 October 2006, Kyiv

Victor E. Kuzmin+380-48-7225127victor@farlep.netA.V. Bogatsky Phys. Chem. Institute NAS of Ukraine Odessa

Talk outline

IntroductionProblem Description & Market NeedSolution of ProblemThe Principle Steps of QSARBrief HIT4QSAR descriptionThe Principle Steps of HIT4QSARExperimental results 1 4The unique and overwhelming HIT4QSAR advantagesAdvantages of HIT4QSAR Relatively Competitive Approaches and ModelsThe comparative analysis of efficacy of HIT4QSARCompetitive MatrixStage of development of HIT4QSARTargeted Market SegmentOpportunity for joint workContact information

Proprietary information statementThe technology material presented in this talk is available for licensing or joint product development.

None of the slides contain any confidential or proprietary information which would prevent patenting the technology.

"There are 10180 possible compounds, 1018 likely drugs, 107 known compounds, 106 commercially available compounds, 106 compounds in corporate databases, 104 compounds in drug databases, 103 commercial drugs and 102 profitable drugs "A. Weininger J. Chem. Inf. Comput. Sci., 37, 138 (1997) Introduction

DRUG DISCOVERYOoms, F. Curr. Med. Chem. 2000, 7, 141-158Problem Description & Market NeedHow to decrease the set of the explored compounds?How to accelerate the drug discovery process? How to reduce financial expenditure?

2

4.196023584

46.5597908385

90.8524998876

135.6851748076

395.4155792157

675.0166188668

1152.3254512383

devlopment cost ($10E06)

1

5.00E-114

196244.20y = 5E-114e0.1337x

19805046.56

198510090.85

1988150135.69

1996350395.42

2000675.02

20041152.33

1

0

0

0

0

0

0

0

, $

2

3

Solution of ProblemSoftware for QSAR

CoMFA - Comparative Molecular Field Analysis (Tripos, USA)CoMSiA - Comparative Molecular Similarity Analysis (Tripos, USA)HQSAR - Holographic QSAR (Tripos, USA)EVA - Eigenvalue Analysis (Tripos, USA)CODESSA Comprehensive Descriptors for Structural and Statistical Analysis (SemiChem, USA)Cerius2 - QSAR software (Accelrys , USA)EMMA Effective Modelling of Molecular Activity (MSU, Russia)DRAGON - QSAR software (MU, Italy)

HIT4QSAR Hierarchical Informational Technology for QSAR (PCI NAS, Odessa, Ukraine)

Quantitative Structure Activity Relationship

QSAR

STRUCTURE

ACTIVITY

text

RELATIONSHIP

The Principle Steps of QSARQSARA = f (S1,S2,S3,,SM)Verification of model

Training setStructureObs.activity12.223.034.1N0.5

Calculation of the structural parametersS1S2S3SM1.21.31.71.92.72.83.42.13.34.80.1-2.112810

Test setStructureObs.activityPred.activity12.12.523.22.634.04.2

PredictionStructureObs.activityPred.activity1?2.62?5.03?6.0

Molecular design

Brief HIT4QSAR description

The principle steps of HIT4QSARMolecular Design of New Perspective Compounds with High ActivityHypotheses about mode of of Biological Activity

Training setMoleculesActivitymiAi

Simplex representation of molecular structure

Weight parameters for atomsChargeLipofilicityPolarizabilityInformational FieldH-Bond

Structure parameters calculationLocal parameters (Quantitative of simplexes)mi Si1, Si2,

Fourier transformation

Integral parametersmi qi1, qi2,

QSARAi =f(Si1, Si2, qi1, qi2, )

PredictionNew moleculesPredicted activity

Statistical characteristicsR correlation coefficientQ cross-validation coefficient

Test setMoleculesActivitymjAj

Experimental results 1ANALYSIS OF THE ANTI-INFLUENZA ACTIVITY (LgTID50)Training setStatistical characteristics of QSAR models

QSARmodelsR2 Q2

2D0.9680.939 4D0.9780.943 3D0.9800.961

Color-coding of molecular fragments with standpoint of their influence on the activity

- enhance the activity - decrease the activityExperimental results 2

The relative influence of molecular fragments on value of activity, lgTID50Experimental results 3

Enhance the activity

2.52.52.0

1.51.40.5Decrease the activity-CH2-CH2-NH--CH2-COOH-CO-NH2-0.5-0.25-0.2

Molecular design of structures with potentially high anti-influenza activity

Structure

Observed

Predicted

356-3054

5.1

5.6

324-2381

5.6

6.0

241-938

3

2.4

470-4121

n.d.

5.5

460-5083

n.d.

6.1

547-7129

n.d.

5.1

The relative influence of some physical and chemical factors into the activity estimated from the HIT4QSAR modelsExperimental results 4

2

10

25

19

11

35

ws

Anti-influenzaSet

250.21copy25.skco

270.251copy27.skco

29-0.251copy29.skco

310.251copy31.skco

322.51copy32.skco

340.711copy34.skco

401.251copy40.skco

410.11copy41.skco

42-0.251copy42.skco

490.331copy49.skco

873.51copy87.skco

880.051copy88.skco

890.151copy89.skco

900.751copy90.skco

94d51copy94d.skco

94o25.11copy94o2.skco

96e2.81copy96e.skco

da1_3-1.51copyda1_3.skco

da1_521copyda1_5.skco

da1_61.31copyda1_6.skco

di3b1.661copydi3b.skco

di3c-1.251copydi3c.skco

di3d1.661copydi3d.skco

di3e-0.751copydi3e.skco

di8b5.61copydi8b.skco

remantodin4.751copyremantodin.skco

ribavirin6.251copyribavirin.skco

28-0.452copy28.skco

300.722copy30.skco

3602copy36.skco

485.332copy48.skco

500.332copy50.skco

rnl01a32copyrnl01a.skco

rnl01c2.22copyrnl01c.skco

20.253

6-0.253

70.253

100.53

120.853

131.333

182.663

19-0.333

24-0.453

260.343

331.53

370.43

380.923

3913

434.953

440.663

451.163

465.333

475.333

510.253

520.373

Model2d

NoNameSetObs.Pred.

1025ws0.2-0.1409

1227ws0.250.2772

1429ws-0.25-0.318

1631ws0.250.1092

1732ws2.52.2808

1934ws0.710.5759

2440ws1.250.5339

2541ws0.10.378

2642ws-0.250.1596

3349ws0.330.1848

3787ws3.52.7533

3888ws0.050.0646

3989ws0.150.9191

4090ws0.751.1481

4194dws54.6403

4294o2ws5.15.5216

4396ews2.82.341

44da1_3ws-1.5-0.7941

45da1_5ws21.6069

46da1_6ws1.31.3923

47di3bws1.661.4462

48di3cws-1.25-1.3111

49di3dws1.661.6773

50di3ews-0.75-0.4258

51di8bws5.65.4838

52remantodinws4.754.9248

53ribavirinws6.256.7312

Intercept0.1092232

Fr3(rf)/B_B_B/1_2s,2_3d/0.21937180.28557269.359RefractionDispersionic10

S_A(chg)/A_D_E_F/1_3s,2_4a/30.09120120.10880513.89Electrostatic25

S_A(chg)/C_D_E_F/1_3s,2_4a/30.0790340.028133093.37Hydrofobic19

S_A(chg)/C_E_E_F/1_2s,3_4s/30.08741130.0042000033.73Shape of molecule11

S_A(chg)/C_E_E_F/2_3s,3_4s/40.12383220.024496925.28Other35

S_A(chg)/C_F_F_F/1_2s,3_4s/30.12393490.22758335.28

S_A(chg)/E_E_F_F/1_4s,2_4s,3_4s/5-0.0838585-0.071216683.5725Electrostatic

S_A(lip)/B_C_D_E/1_2s,2_4s,3_4s/60.22102250.51942589.42

S_A(lip)/C_C_D_D/1_2s,2_3s,2_4s/5-0.0592314-0.020847112.52

S_A(lip)/D_E_E_E/1_2s,1_3s,1_4s/50.34823331.08578214.8427Lipofilic

S_A(type)/C.2_C.3_C.3_H/1_4s,2_3s/30.17083150.14863537.28

S_A(type)/C.2_C.3_H_O.3/1_4s,3_4s/4-0.1572247-0.057252466.7

S_A(type)/C.2_H_H_O.3/1_2s,3_4s/30.17013380.27063147.25

S_A(type)/H_H_O.3_O.3/1_3s,2_4s/30.19235610.60329928.2

Fr3(type)/C.3_H_O.3/1_3s,2_3s/0.21822140.69690529.339Atom nature

Model2d

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Pred.

Observed

Predicted

Observed vs predicted values of LgTID50

Selected_3d

0

0

0

0

0

3

CaseAnti-influenza(Pred.)T[1]T[2]T[3]Dist, sigmaConformerActivityTotal

25.03284.0247-2.7502-0.98581.902_0140.27935.3121

63.16831.944-1.4221-0.67570.206_0160.29993.4682

73.18321.8402-1.1192-0.5546007_007-0.88112.3021

102.63721.3559-1.2301-0.2092-0.310_015-0.40192.2353

125.49134.8818-3.7685-1.87372.912_0170.70816.1994

132.74521.4078-1.0957-0.2286-0.313_0020.08992.8351

184.03322.4448-0.4756-1.11880.318_0130.35614.3893

192.58391.1152-1.01650.6374-0.419_0050.92193.5058

242.58391.1152-1.01650.6374-0.424_0070.52693.1108

250.2914-0.968-0.69510.6943-0.625_0170.25180.5432

265.183.826-1.6383-1.2351.426_0010.82966.0096

270.163-1.3034-0.40311.5716-0.127_0010.25750.4205

280.0451-1.0736-1.05220.7633-0.428_001-0.1582-0.1131

290.0271-1.0823-1.07460.7666-0.429_0170.66450.6916

300.8633-0.62-0.51371.2644-0.530_0010.79981.6631

310.4713-0.8815-0.47110.662-0.831_0150.84771.319

323.13840.58772.5324-0.38480.232_0050.48343.6218

334.56153.6995-2.8866-1.22511.833_015-0.71123.8503

340.8453-0.6287-0.53611.2677-0.534_0121.13151.9768

360.4174-0.9075-0.53830.6717-0.736_0331.01581.4332

376.5175.6099-3.1935-2.10233.137_0010.40896.9259

383.98122.4456-0.6947-0.94530.338_0120.68784.669

391.84180.1971-0.22940.7996-139_0020.49692.3387

400.6834-0.7065-0.73771.2967-0.440_0020.08240.7658

410.2529-1.2602-0.29111.5555-0.241_0160.03130.2842

42-0.1789-1.4677-0.82871.633042_0200.22230.0434

430.3969-1.191-0.11191.5296-0.243_024-0.17570.2212

440.3186-0.9886-0.48360.5263-0.744_0660.92091.2395

450.2374-0.994-0.76230.704-0.645_0681.11761.355

460.2374-0.994-0.76230.704-0.646_0321.0271.2644

470.2374-0.994-0.76230.704-0.647_0470.13240.3698

484.93983.3932-1.55970.1203148_0511.36186.3016

490.2374-0.994-0.76230.704-0.649_0020.07910.3165

500.2374-0.994-0.76230.704-0.650_0020.08790.3253

513.16791.0679-0.37962.94460.651_004-0.96752.2004

521.1643-0.3685-0.79851.9386-0.152_0220.10341.2677

872.23240.11591.5449-0.2856-0.587_0031.48593.7183

880.1918-1.0202-0.78470.6659-0.688_0010.41930.6111

890.493-0.8502-0.31890.2413-0.989_0881.44731.9403

900.7474-0.7107-0.13940.3808-190_2521.46862.216

94d4.8343.713-2.7381-0.06191.694d_0120.65575.4897

94o25.20713.7099-1.6181-0.33821.294O2_0111.10016.3072

96e2.61560.9355-0.2970.4527-0.896e_0060.98653.6021

da1_3-0.5682-1.6002-0.72490.041-0.4DA1_3_036-0.0205-0.5887

da1_51.2297-0.87311.66420.3111-0.3DA1_5_0170.99682.2265

da1_60.8254-1.03481.0870.326-0.5DA1_6_0241.09551.9209

di3b1.7088-0.45290.54562.71290.4di3b_0170.78262.4914

di3c-1.4117-2.0107-1.70830.08020.3di3c_0151.0974-0.3143

di3d1.3505-0.81381.67520.5877-0.2di3d_0210.95872.3092

di3e-0.8853-1.871-0.74940.083-0.2di3e_0210.95780.0725

di8b5.12253.7828-2.34480.27621.5di8b_0070.67075.7932

remantodin3.70360.90143.1975-0.6860.8remantodin_0011.26964.9732

ribavirin6.09752.54581.52345.7812.9RIBAVIRIN_2361.34677.4442

rnl01a2.32030.8475-1.11491.1313-0.3RNL01A_0030.96613.2864

rnl01c1.90710.3085-0.70851.4796-0.4rnl01c_0551.2293.1361

267101213181924252627282930313233343637383940414243444546474849505152618788899094d94o296eacyclovird015d016d017d027da1_0da1_3da1_5da1_6di3adi3bdi3cdi3ddi3edi8bremantodinribavirinrl230rnl01arnl01crnl02arnl03aRNL05a

Anti-influenzaUnknown0.25-0.250.250.50.851.332.66-0.33-0.450.20.340.25-0.45-0.250.720.252.51.50.7100.40.9211.250.1-0.254.950.661.165.335.335.330.330.330.250.3703.50.050.150.7555.12.8000000-1.521.301.66-1.251.66-0.755.64.756.25032.2000

Fr3(rf)/B_B_B/1_2s,2_3d/2D4444444440400000040044400000000400440000044490000000000000405022004

S_A(type)/C.2_H_H_O.3/1_2s,3_4s/32D0000000000000000020000000000000400000000044000000000000000403022000

S_A(type)/C.2_C.3_C.3_H/1_4s,2_3s/32D04006260004000000000810000000000400000000046810000000000000804000004

S_A(chg)/A_E_F_F/1_2s,1_4d/42D1420181418142000016000000180014220000000001200000000012166000000000000001000040000

S_A(chg)/C_D_E_F/1_3s,2_4a/32D3400018001818018000000240018000000000012003200000012120000000000000002800066000

S_A(chg)/A_D_E_F/1_3s,2_4a/32D400012000004000000400160000000000400000000084000000000000000400010000

S_A(type)/H_H_O.3_O.3/1_3s,2_4s/32D0000000000001110001000010000000100000000011000000000001100103011000

Fr3(type)/C.3_H_O.3/1_3s,2_3s/2D0000000000000000000000000000000000000000000000000000002000003000000

S_A(type)/C.2_C.3_H_O.3/1_4s,3_4s/42D0000000000001818400240000400000000000000140000000000000002600000001000

S_A(lip)/D_E_E_E/1_2s,1_3s,1_4s/52D0000000000000000200000000000000000000100000000000000000000030000000

S_A(type)/C.3_C.3_N.3_O.3/1_4s,2_4s/42D00000000000000000000000000000000000000000000280034568888816001000000

S_A(type)/C.3_C.3_C.3_N.3/1_3s,2_3s,3_4s/52D0000000000000000200000000000000000000100000000000000000000010000000

S_A(lip)/B_C_D_E/1_3a,3_4s/42D0000000000040000000000004440000000840000000000000000000000000000008

S_A(chg)/A_E_F_F/1_4a,2_3s/32D88888828880202000001040888210210848002226600000000000000000000000000000010

S_A(lip)/C_D_E_E/1_3s,2_4s/32D404864322444762424650382826202666301820102124440480642400016004200132330327200080007860000960206000060030

S_A(chg)/E_E_F_F/1_4s,2_4s,3_4s/52D2222224220200000020022200002000000200000002024000088644444001000000

S_A(lip)/B_C_D_E/1_2s,2_4s,3_4s/62D0000000000000000000000000000000000000302200000000000000000030000006

S_A(chg)/C_E_E_F/2_3s,3_4s/42D00000044000440000000000000000000032000000000032000000003628000240000000000

S_A(type)/C.3_H_H_O.3/1_4s,3_4s/42D000000000000000000000000000000000000000000000000000000620000029000000

S_A(lip)/C_C_D_D/1_2s,2_3s,2_4s/52D08001406001240000000008600000000040000480000868320241220161614102018121212002400000

S_A(chg)/C_E_E_F/1_2s,3_4s/32D114547890661381766666013240002400962206610212612641290662242666418121429800300169616000000013513100014403200014300084

S_A(lip)/C_D_D_D/1_2s,1_4s,3_4s/62D0400800001204444412044080000000000000024200040008161612840280000000000000

S_A(chg)/C_F_F_F/1_2s,3_4s/32D0000000000000000000000000000000000400000000000000004300040000000000

I.Ix3D719.95671026.096456.7328514.00831167.125747.2079838.57111421.9261640.1243.13091177.7831423.3668.36191055.581851.6617521.3754428.59071022.22475.99841073.9241315.5241486.9381885.7713.31976673.69569.67892192.5368733.3882295.8942350.8271638.842399.28046.71953.458911164.9052231.457107.121721.8792553.78271190.8074492.7562819.4916980.5883128.95211049.374932.8893723.41131201.3871223.6331141.505556.5468157.4016283.9754127.709262.6638

I.Iy3D1508.5431786.463392.9852297.3171495.9331775.3821561.7761514.6932114.688888.34811453.4082166.8832052.8071440.7431147.1511064.775941.63153325.717585.38931296.1041930.2061761.0682336.98417.8118805.7833503.3851445.877951.2476396.0547566.80361600.06428.6524434.1118641.68233911.6842960.32115.5122129.79760.87151209.7174879.7667920.68351127.081217.191239.5551069.5981050.4731280.5271437.7581276.949943.6837197.5005323.0818217.9594325.8925

I.Iz3D3087.2124687.4744128.543249.1875839.9598847.8386141.9514414.6794543.61632.1792280.4972818.2872547.5842794.95411145.6912302.259238.1994663.67316584.0916658.885982.3858023.96710154.61978.50961797.5911340.8751799.8822084.2910199.27742.6441866.688818.981960.37241625.5436730.2215379.374367.37862.6525872.7957479.92831774.4182184.1843732.1021512.5143205.9421995.4433684.7432165.4122770.3942191.0391888.635590.85251611.633268.1123530.428

I.Ix/Iy3D0.4772530.57437380.13461090.22374280.78019850.42087150.53693450.93875530.77557550.27368870.81035950.65684190.32558450.73266470.74241490.48965770.45515750.30736840.81313130.82857840.6815460.84433850.80692630.0079456010.091457590.13842070.13316270.77097510.74710440.61895720.39926130.93147830.015477580.083310550.29780130.75378890.92736310.16856510.88354470.90983080.56009870.89009050.87002530.10594250.84657320.87218680.68865320.93819720.85107030.89393140.58975990.79696810.87895820.58593030.8059829

I.Ix/Iz3D0.23320610.21890160.11062820.1581960.19985160.08445090.13653170.32209040.36096930.14896090.51645880.50502290.26235120.3776740.076411720.04238050.046393310.21918780.02870210.064465520.21989960.18531210.18570590.0033926760.040996540.051965270.10697190.35186480.029011510.045311030.34223440.045275120.0069962450.032886790.17308570.41481720.29159090.025362760.061621190.39757480.27770010.37519350.26274420.085256840.32732160.46750990.19632610.55480750.44168190.52098810.29468210.26639740.17620380.03907730.0744

I.Iy/Iz3D0.48864250.38111360.82183660.70704380.25615470.20065720.254280.34310370.46542120.54427120.63732060.76886520.80578550.515480.10292320.086551290.1019280.71311110.035298240.077802570.32264830.2194760.23013990.42698790.44825740.37541540.80331730.45638930.038831930.073205430.85716910.048605660.45202440.39474940.58121190.55030940.31443020.15046270.069743140.43697660.49580570.42152290.30199610.80474650.38664310.53602040.2850870.59135490.51897230.58280550.49966450.33426360.2004690.066692750.09230965

I.Asphericity3D0.15118130.16273780.28498940.22191940.1877660.3104610.23823410.11986680.091526850.22440390.043263630.044938620.14426840.082953160.33466450.40631870.39495540.16852770.45302180.36155250.16635540.20448190.20162020.61222340.41062660.38012060.28897730.095209910.45049070.39904640.10441250.40953460.5712460.43813310.20128630.070237410.13530850.47631760.37010570.084508820.1248650.092119350.14833590.32228030.11083210.058712020.18543960.039815960.065559130.045447340.11625280.14119430.21518920.41630680.3413281

I.AW1D413474479419457523459461493291415465392393432437409463433476483545645195251223327347375375374312191239534599139151131153311356426263397366350378434376324179244241255

I.Rf1D94.55195105.5599101.937990.05195105.6959115.6519102.137996.42594109.139967.3959791.8949492.8239587.3019686.4239686.9019584.22396101.251995.4379486.0239684.70196112.0959126.1819143.1437.69454.8939848.0959971.8939771.6939670.5799770.5799771.4579769.3729743.0079935.49401112.1039128.695939.92232.30832.50831.40871.1519679.61596101.531963.2369894.7799585.7589685.5019484.38794101.587987.9459476.3299650.6219847.5029948.7509953.05099

I.EN1D141.6999160.7699151.83131.05159.13169.05155.53144.2899142.5699103.98138.1899148.9699139.3199137.6099131.92135.0699156.75140.48130.21129.38168.63193.81190.7759.5587.3499773.63111.45107.75105.83105.83107.54106.299966.5757.01165.7185.3363.3900150.1200153.8200152.55001108.0999123.64150.54105.84154.23137.73142.3199140.3999168.1999143.9999116.759979.8399976.1673.2599980.20998

I.XLogP2D4.481.944.044.441.926.552.541.982.46-1.122.651.832.841.363.761.274.454.012.283.672.132.16.490.191.69-1.883.63.252.912.914.391.960.770.13.428.621.850.770.310.261.641.852.86-2.24-0.3-0.37-2.91-2.5-1-3.253.862.37-3.092.432.54

I.Dipole_Moment3D1.1920753.6407371.1893871.9539791.4669522.6262320.84499282.8460142.6709152.2063280.87626054.4717991.2732061.683081.3011262.3690041.7963462.0310582.4577951.304020.87808982.5885151.3467610.26379361.0306910.97721111.1261032.3046823.4478650.54234914.3615321.6775161.3013245.405073.3891172.2436830.46010460.39013310.72581373.7586821.5621110.40128481.0530840.44000971.2173912.5979911.458972.132910.33371833.8669632.069050.46192280.56934220.41509490.6027005

The unique and overwhelming HIT4QSAR advantages are:

simplex representation of molecular structure (SiRMS), Fourier transformation of structure parameters spectrum, characteristics of molecular informational field all of them is providing universality, diversity and flexibility of description for compounds of different structural types;

HIT4QSAR that depending on the concrete aims of research allows to construct the optimal strategy of QSAR models generation, avoiding at the same time the superfluous complication that doesn't results in the adequacy increase.

on the every stage of HIT4QSAR usage we can determine the molecular structure features that are important for the studied activity, and exclude the rest. It shows unambiguously the limits of expedient QSAR models complication and allows not to waste superfluous resources for needless calculations.

Unlike HIT4QSAR, a majority of descriptors in CODESSA, EMMA, DRAGON have interpretation difficulties and little suitable for molecular design. These approaches are applicable, mainly, for an activity prediction. HIT4QSAR does not have the restrictions of such well-known and widely used approaches as CoMFA (Comparative Molecular Field Analysis), CoMSIA, and HASL, usage of the lasts is limited in the structurally homogeneous set of molecules and only one conformer. HIT4QSAR has not the HQSAR restrictions (only topological representation of molecular structure) and lacks (ambiguity of descriptors formation when procedure of hashing of molecular holograms is realized). Besides, on the contrary to HQSAR, in SiRMS, different physical and chemical properties of atoms (charge, lipophilicity, etc.) can be taken into account. Advantages of HIT4QSAR Relatively Competitive Approaches and Models (CoMFA, CoMSiA, HASL, CODESSA, EMMA, DRAGON, HQSAR)

Angiotensin Converting Enzyme (ACE) inhibitors Work set 76 compounds Test set 38The comparative analysis of efficacy of HIT4QSAR Q2R2Results from Sutherland J.J.; OBrien L.A.; Weaver D.F. A Comparison of Methods for Modeling Quantitative StructureActivity Relationships. J. Med. Chem. 2004, 47, 5541-5554CoMFA - Comparative Molecular Field AnalysisCoMSiA - Comparative Molecular Similarity Indices AnalysisEVA - Eigenvalue AnalysisHQSAR - Holographic QSARCerius2 - QSAR software

Our models are more adequately and have more high statistical rates.HIT4QSAR on Base Simplex Representation of Molecular Structure

R2

0.8

0.76

0.84

0.84

0.82

0.857

0.945

R2

1

R2Q2;10R2test

CoMFA0.80.690.49

CoMSIA0.760.660.52

EVA0.840.70.36

HQSAR0.840.720.3

Cerius0.820.720.51

SiRMS 2D0.860.810.54

SiRMS 3D0.950.920.56

1

0

0

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

0

0

3

R2

0.8

0.76

0.84

0.84

0.82

0.857

0.945

0.911

0.975

R2

2

0.69

0.66

0.7

0.72

0.72

0.812

0.917

1

R2Q2;10R2test

CoMFA0.80.690.49

CoMSIA0.760.660.52

EVA0.840.70.36

HQSAR0.840.720.3

Cerius0.820.720.51

SiRMS 2D0.860.810.54

SiRMS 3D0.950.920.56

1

0

0

0

0

0

0

0

0

0

2

3

Competitive Matrix

Criterion

HIT4QSAR

CoMFA

HASL

GRID

MolLat

CODESSA

EMMA

DRAGON

HQSAR

Adequcy of representation of molecular structure

1D-4D

1D - 4D

EMBED MSPhotoEd.3

EMBED MSPhotoEd.3

EMBED MSPhotoEd.3

3D

2D

3D

2D

Molecular alignment problem

No

Yes

No

No

Explicit consideration of stereochemistry and chirality

Yes

Partly

No

No

Consideration of physical-chemical properties of atoms

Charges, lipophilicity, polarizability etc.

Yes

Partly

Partly

No

Possibility of molecular design

Yes

Partly

No

Partly

Impair the method quality

Improoving the method quality

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_1081156348.bin

_1081156252.bin

_1081156328.bin

Stage of development of HIT4QSAR Here are presented high activity compounds, which was designed by means of developed HIT4QSARHIT4QSAR is realized as software, tested, available for demonstration, field testing was carried out.

Targeted Market Segment

The developed HIT4QSAR allows to decide any tasks structure property. On the basis of this technology, carry out of molecular design of various compounds is possible with the complex of useful properties. We have experience of molecular design of perspective drugs (antiviral, antitumor, psychotropic, antimicrobial, anti-inflammation, etc), pesticides, optical materials, complexones, food supplements, quenching agents, etc. The results of the use of our technology can be interesting and useful for all, who carry out development of new drugs, materials, reagents, etc.

Potential consumers of HIT4QSAR are pharmaceutical companies and developers of software for QSAR. Cost of project that related to the prediction and design of new drugs, substances and materials depends on the amount of concrete tasks, presence and content of information for the construction of training set, special requirements to the results. Rough estimate 10 000 $ for: test set 30-50 compounds, level of modeling - 2D, term of contract - 1 month

Opportunity for joint workWe seek a potential clients, which need the results of the use of our technology. We are ready to vend the service structure optimization, molecular design, prediction of new compounds with complex of demand properties by means of HIT4QSAR.

We are ready for collaboration with colleagues chemists- synthesist and specialists of investigation different properties of substances (biologist, virologists, pharmacologist, etc) for carry out joint projects.

Contact informationDoctor of chemical scienceVictor E. KuzminHead of laboratory on theoretical chemistryA.V. Bogatsky Phys. Chem. Institute NAS of Ukraine, Odessa

+380-48-7225127victor@farlep.net

Thank you for attention

Design, development and commercialization of a drug is a tedious time-consuming and cost-intensive process. In 1950 it was estimated that 7000 compounds had to be isolated or synthesized and then tested to obtain a suitable drug. The challenge is becoming more difficult : 10000had to be evaluated in 1979 and this number could be as high as 20000 today.