rapid drug discovery at nimbus and the role of seurat · 2017-06-27 · seurat’s role at nimbus -...

Matthew D. Wessel

ChemAxon UGM Boston

September 2012

Rapid Drug Discovery at

Nimbus and the Role of Seurat

Nimbus Breakthrough Approach

• Unlocking well-validated, previously

inaccessible disease targets – IRAK4: in vivo proof of concept in 9 months

– ACC: first drug-like allosteric inhibitors

– State-of-the-art computational platform

• Radically virtual

• Innovative partnering model

For more information, please visit:

http://www.nimbusdiscovery.com

Productivity of Nimbus Approach

Potent, drug-like IRAK4 Inhibitors in 12 months

0 2 4 6 8 10 12

3,000 60,000

Lead Candidate

Months

Ideas

In vivo PoC

Milestone

Achieved

Initiate HTL

40 271 Compounds

8,000 nM 100 nM <10 nM Potency

1.3MM

300+

Seurat’s Role at Nimbus – A Decision Support Tool

Links to Glide docked

poses and other useful

computational results

Data access and analysis is facile

Calculated binding scores

and experimental data

side by side

Seurat’s Role at Nimbus - Live Reports for Data Sharing

Your reports

Project reports

Other Seurat user’s reports

Update Policies:

When Opened

Nightly

Never

Double click

The Nimbus Virtual and Real Space

>70K

Ideas DB Compound Whiteboard

<1K

Real DB

Compound idea and

associated computational

data registered in Ideas DB

Compound synthesized

and registered in Real DB

Docking

Score

Water

Map

ADME

predictions Tracking Data

-5.43

Kcal/mo

l

File

URL

Caco-2

permeability

Scientist, Library ID,

Date, etc…

Selection

Process

Automated

data transfer

Structure

Check

Seurat’s Role at Nimbus – Project Progression

R-group analysis is easy to do and informative

• Organization of existing data

• Enumeration of empty cells

• Decision support environment

R1 groups

R2 g

roups

SAR Matrix new features coming soon

Add data to hypotheticals, improved organization

Color coded by property, filtered by ranges, etc

Acknowledgements

Donna Romero

Ron Wester

Jonathan Montagu

Rosana Kapeller

Gerry Harriman

Craig Masse

Shaughn Robinson

Mee Shelley

Amy Rask

Jeremy Greenwood

Leah Frye

James Baxendale

Scott Becker

http://www.nimbusdiscovery.com http://www.schrodinger.com/seurat

Target Target

Indication

Virtual

Screen Hit

Lead

Candidate

Development

Candidate

Nimbus Discovery Vision October 2010

IRAK4

Inflammation/cancer

ACC

Obesity/cancer

Multiple targets identified with unexploited

insights into potency and selectivity

Target Target

Indication

Virtual

Screen Hit

Lead

Candidate

Development

Candidate

Significant Achievements Since Oct. 2010

Target 3 Not Disclosed

Target 4 Not disclosed

IRAK4 12 Mos

Inflammation/cancer

ACC

Obesity/cancer