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Rongene Pharma introduction
 

Rongene Pharma introduction

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Rongene Pharma is a global pharmaceutical firm launching the innovative drug...

Rongene Pharma is a global pharmaceutical firm launching the innovative drug
discovery platform. Our platform assists our clients with customized
lead compounds and preclinical drug candidates. Our clients include
pharmaceutical, biotech companies, research institutes, universities,
and governmental organizations etc. Rongene also provides a
comprehensive portfolio of services in early stage drug discovery and
development in an efficient and cost-effective manner.
http://www.rongene.com

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    Rongene Pharma introduction Rongene Pharma introduction Presentation Transcript

    • Rongene Pharma Co., Ltd Mar. 2012
    • Outline
    • About Rongene Target Library Hit to Lead Preclinical ClinicalAnalysis Screening Lead Optimization Evaluation Trial
    • Marketing Position Research Pharma & Institutes Biotech. Leads Rongene Pharma In Vivo In Vitro Computer-aided Drug Design
    • Complex & Innovative Drug Design PKKB TCM 1000+ Cores
    • 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
    • Prediction models forADMET properties Caco-2 permeability MDCK permeability Permeability Intestinal absorption Blood-brain partitioning Transporters (P-gp) Bioavailability pKa Molecular logP and logD Properties Solubility Clearance Half life Volume of distribution Metabolism Carcinogenicity Toxicity Mutagenicity Others
    • Lead OptimizationPhysiochemical Properties Pharmacology MetabolismMolecular weight Administration MetabolismlogP (experiment) Pharmacology Half-timelogP (predicted, AB/logP) Status CYP450 metabolite profilepka (experiment) Absorption drug-drug interactionlogD (pH=7, predicted) Intestinal absorption ExcretionSolubility (experiment) Absorption (description) ExcretionlogS (predicted, ACD/Labs)(pH=7) Caco-2 permeability Urinary excretionlogSw (predicted, AB/LogSw 2.0) Human bioavailability ClearanceSw(mg/ml) (predicted, ACD/Labs) Distribution ToxicitySw(predicted) Plasma protein binding Description of toxicityNumber 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) genotoxicityTPSA Area under the curve (AUC) aquatic toxicity
    • 药物开发技术路线图
    • Key Distinctions Precise Drug Design Key Distinctions Assay Efficient Screening Zebrafish
    • Outline
    • 1,040,000 compounds Virtual Screening 193 compounds BioassayCase I:ROCK-based 34 compounds Evaluationdrug design& Screening 8 hits Hit to Lead 4 leads Optimize
    • Case I :ROCK-based drug design & Screening IC50 = 13.7 mM LD50 > 2000 mg/kg TH-004
    • Case I: ROCK-based drug design & Screening EC50 (mM) Fasudil
    • Control1 μM Lipitorfor 24 hours 10μM TH-004 for 24 H TH-004
    • Case II Camptothecin Derivatives
    • Case II CPT derivativesIn Vitro MTT Assay
    • Case II In Vivo Xenograft-- Lung Tumor In Vivo xenograft vs Lung Tumor Fig 7. Growth inhibitory effect of topotecan derivatives on NCI-H460 human lung cancer nude mice xenograft model 3000 Model Topotecan 2mg/kg Compound I 0.3125mg/kg 2500 Compound II 2.5mg/kg Compound III 0.78125mg/kg 2000 (mm3)Tumor volume 1500 1000 500 0 0.5 1 1.5 2 2.5 3 3.5 4 Weeks
    • Case III:Structure-Based Design of Peptides against G3BP Protein-protein docking & Free energy calculation design flow
    • Case III :Structure-Based Designof 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 Target Library Hit to Lead Preclinical ClinicalAnalysis Screening Lead Optimization Evaluation TrialTH-004 (Cerebral hemorrhage)HY-029 (Cerebral hemorrhage)HY-001 (Anticancer)TH-007 (Anticancer)ML-019 (Anti-angiogenesis)MYSL-003 (Anti-atherosclerosis)
    • Software copyright 1Patents 5Publications 160+
    • Contact Rongene Pharma Co., Ltd Email: info@rongene.com Phone: 86-512-6588 2039 Cell: 86-137 2522 8971 Web: www.rongene.com 8, Dongfu Rd, Suzhou Industrial Park, Suzhou, Jiangsu, China 215123