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Rongene Pharma is a global pharmaceutical firm launching the innovative drugdiscovery platform. Our platform assists our clients with customizedlead compounds and preclinical drug candidates. Our clients includepharmaceutical, biotech companies, research institutes, universities,and governmental organizations etc. Rongene also provides acomprehensive portfolio of services in early stage drug discovery anddevelopment in an efficient and cost-effective manner.http://www.rongene.com
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Rongene Pharma Co., Ltd
Mar. 2012
Outline
Clinical
Trial
About Rongene
Target
Analysis
Library
Screening
Lead
Optimization Preclinical
Evaluation
Hit to
Lead
Marketing Position
Rongene Pharma
Pharma &
Biotech.
Research
Institutes
Leads
In Vivo In Vitro
Computer-aided Drug Design
Complex & Innovative Drug Design
1000+ Cores
PKKB TCM
Lead Selection Factors
Target potency Integrity of compounds
Target selectivity (Kinase panel) Chemical tractability
Human liver enzyme inhibition Mechanism of action
Toxicity in human liver cells Biophysical assay
Permeability in intestine cells IP assessment
Mutagenesis potential Drug-like properties
Cardiac liability Zebrafish models
Half life Clearance
Volume of distribution
Metabolism
Prediction models for
ADMET properties
Bioavailability
Toxicity Carcinogenicity
Mutagenicity
Others
Caco-2 permeability
MDCK permeability
Intestinal absorption
Blood-brain partitioning
Transporters (P-gp)
Permeability
Molecular
Properties
pKa
logP and logD
Solubility
Lead Optimization
Physiochemical Properties Pharmacology Metabolism
Molecular weight Administration Metabolism
logP (experiment) Pharmacology Half-time
logP (predicted, AB/logP) Status CYP450 metabolite profile
pka (experiment) Absorption drug-drug interaction
logD (pH=7, predicted) Intestinal absorption Excretion
Solubility (experiment) Absorption (description) Excretion
logS (predicted, ACD/Labs)(pH=7) Caco-2 permeability Urinary excretion
logSw (predicted, AB/LogSw 2.0) Human bioavailability Clearance
Sw(mg/ml) (predicted, ACD/Labs) Distribution Toxicity
Sw(predicted) Plasma protein binding Description of toxicity
Number of hydrogen bond donors Volume of distribution (Vd) LD50 (rat)
Number of hydrogen bond acceptors blood-brain-barrier permeability LD50 (mouse)
Number of rotatable bonds Transporter protein binding (P-gp) genotoxicity
TPSA Area under the curve (AUC) aquatic toxicity
药物开发技术路线图
Key Distinctions
Efficient Zebrafish
Key Distinctions
Precise Drug Design
Assay Screening
Outline
34 compounds Evaluation
Hit to Lead
1,040,000 compounds
Virtual Screening
193 compounds Bioassay
8 hits
Optimize
4 leads
Case I： ROCK-based drug design & Screening
Case I ：ROCK-based drug design & Screening
LD50 > 2000 mg/kg
IC50 = 13.7 mM
TH-004
Case I： ROCK-based drug design & Screening
EC50 (mM)
Fasu
dil
Control
10μM TH-004
for 24 H
1 μM Lipitor
for 24 hours
TH-004
Case II Camptothecin Derivatives
Case II CPT derivatives
In Vitro MTT Assay
Case II In Vivo Xenograft
-- Lung Tumor
Figure 4
In Vivo xenograft vs Lung Tumor
Fig 7. Growth inhibitory effect of topotecan derivatives on NCI-H460 human lung cancer nude mice xenograft model
0
500
1000
1500
2000
2500
3000
0.5 1 1.5 2 2.5 3 3.5 4
Weeks
Tu
mo
r v
olu
me（
mm3）
Model
Topotecan 2mg/kg
Compound I 0.3125mg/kg
Compound II 2.5mg/kg
Compound III 0.78125mg/kg
Protein-protein docking & Free energy calculation design flow
Case III：Structure-Based Design of Peptides against G3BP
Case III ：Structure-Based Design of Peptides against G3BP
The sequences and biological assays for three peptides and cis-platin
Case III ：Structure-Based Design of Peptides against G3BP
JCIM 50th celebration cover
In preclinical anticancer evaluation
Pipelines
TH-004 (Cerebral hemorrhage)
ML-019 (Anti-angiogenesis)
MYSL-003 (Anti-atherosclerosis)
HY-001 (Anticancer)
TH-007 (Anticancer)
HY-029 (Cerebral hemorrhage)
Clinical
Trial
Target
Analysis
Library
Screening
Lead
Optimization Hit to
Lead
Preclinical
Evaluation
Software copyright 1
Patents 5
Publications 160+
Contact
Rongene Pharma Co., Ltd
Email: [email protected]
Phone: 86-512-6588 2039
Cell: 86-137 2522 8971
Web: www.rongene.com
8, Dongfu Rd, Suzhou Industrial Park,
Suzhou, Jiangsu, China 215123
