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Our clients

In vitro facilities at o2h discovery have been developed to provide faster decision-making points for our chemistry clients.

We have doubled both our capacity as well as capability to include a range of pharmacology services to evaluate activity and/or potential liability of compounds. Our purpose-built labs include industry standard formats of fluorescence, luminescence and absorbance to help develop and optimise biochemical and/or cellular assays in a range of therapeutic areas.

ADME (Absorption, Distribution, Metabolism, and Excretion) is a crucial concept in pharmacology and drug development. It describes the fate of a drug within the body, from its administration to its eventual elimination, and how the body handles the drug during this process.

In the process of new drug development, in vitro (ADME) plays an important role as an important tool for screening, from hits discovery to candidate compound selection, especially in the process of compound optimization. It helps the discovery and optimization of lead compounds and helps researchers quickly understand the properties of compounds, so as to accelerate the acquisition of candidate compounds. 

Biotech companies might face several challenges related to ADME studies during the drug discovery process. These challenges can impact the success of drug development and require careful consideration and strategic approaches. Some of the key challenges include Predictive models, Species differences, Human variability, In vitro to in vivo correlation, among others.

To address these challenges, at o2h discovery, we have a multidisciplinary approach, combining expertise in chemistry, Biology, DMPK and computational modeling.

We have well established assays across the species to overcome species differences; o2h discovery uses pooled donor microsomes and plasma to reduce human variabilities; partner CRO (for in vivo) can help to check IVIV correlation and o2h can suggest follow up assays.

o2h discovery offers following assays:

ADME assays
Solubility (thermodynamic, kinetic), Log P/Log D studies, permeability (PAMPA), CYP inhibition (fluorescence, LCMS/MS based), microsomal stability, plasma stability, hepatocyte stability, plasma protein binding.

Target-based assays
Enzymatic/kinase assays, binding assays, GPCR assays

Cell-based assays
ELISA, proliferation/cytotoxicity, phosphorylation status, cytokine production assays using hPBMCs, signal transduction assays.

o2h discovery has worked on more than 40 projects and provided customized service for each client. We successfully delivered over 3000 ADME studies across different projects.

Below are some of the examples of how we have helped our collaborators overcome challenges in ADME:

For Microsomal stability – if cmpds are self degrading – we can check buffer stability to prove. For protein binding study – less recovery of cmpds can be confirmed by checking plasma stability of cmpds. Moreover o2h can predict possible  fragments in plasma or microsomal stability study with help of Lightsight software.

Before proceeding Caco2 or any permeability studies – o2h discovery recommends to run solubility study and based on outcome suggest final assay concentration.

For IVIV discrepancies – o2h discovery can check and perform blood plasma partitioning, S9 fraction, microsomal binding studies. o2h discovery can check molecule clearance by urine, bile or fecal analysis with help of partner CRO.

Equipment, capabilities, skillset we have available to perform ADME:

Our ADME screening service can provide customized solutions to meet the specific program needs of different customers.

1. Physicochemical properties – A  specific characteristic of a molecule/NCEs that influence their behavior. These parameters play a crucial role in determining the pharmacokinetic profile and overall fate of a drug within the body. At o2h discovery, a number of assays to study physicochemical properties are available including:

  • Kinetic, high-throughput and thermodynamic solubility at different pH, SIF and SGF
  • Chemical stability at various pH, SIF and SGF
  • Log D/LogP, Chrom Log D

2. PermeabilityMedicinal chemists consider permeability during drug design and optimization to ensure that drug candidates have adequate properties for efficient absorption and distribution. Understanding the permeability of NCEs are essential for predicting their behavior in the body and optimizing their pharmaceutical properties. To understand permeability along  with other ADME characteristics, we can run below assays:

  • Caco-2 bi-directional permeability and efflux ratio
  • MDCK (native)
  • MDCK-MDR1
  • PAMPA 

3. Distribution – It refers to the process by which a drug or xenobiotic is transported and dispersed throughout the body after absorption. Once a drug enters the systemic circulation, it is distributed to various tissues and organs, including the site of action or target, as well as non-target tissues.

  • Plasma protein binding
  • Whole blood binding
  • Microsomal binding
  • Blood to plasma partition

4. Metabolism studies – Metabolism refers to the chemical transformations that a drug undergoes in the body, primarily in the liver, to convert it into different metabolites (through the cytochrome P450 (CYP) family of enzymes as well as non-CYP enzymes, including esterases and Phase II glucuronosyl- and sulfo-transferases for instance). Understanding drug metabolism is essential because it impacts the drug’s efficacy, toxicity, and overall pharmacokinetic profile.

  • Half -life and clearance prediction in microsomes (phase I metabolism)
  • Half -life and clearance prediction in hepatocytes (Phase I and II metabolism) 
  • Half -life and clearance prediction in S9 (Phase II metabolism)
  • Stability in plasma, blood
  • Stability in blood
  • Non CYP based stability by AO, FMO

Our intestinal metabolic stability stability assay uses subcellular fractions such as microsomes from human and all preclinical species to assess intestinal metabolism.

5. Drug Drug Interaction – DDI studies can predict a compound’s likelihood to cause drug-drug interactions via up- or down-regulation of drug-metabolising enzymes or drug transporters or their activities. We can provide below services:

  • CYP Inhibition
  • CYP Induction
  • TDI CYP Inhibition

6. Metabolite Identification (Met-ID) – Analyzing and identifying the metabolites produced when a drug undergoes metabolism in the body. This is essential for understanding a drug’s metabolic pathways and potential toxicity issues. o2h can run study using samples of microsmal, hepatocyte and plasma stability.

o2h discovery is equipped with multiple biological analysis instruments and equipment.

Mass spectrum:

  • Sciex 3200 Qtrap +hPLC (Agilent 1260 infinity II)
  • Sciex 4500 Qtrap +UPLC (Sciex Exion LC)

To know more about our ADME service offerings or to request our brochure, please reach out to us at discovery@o2h.com.

our team

prashant shah

Prashant Shah

CEO - o2h discovery and Co-Founder - o2h group

Prashant's Biography

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Prashant Shah

CEO - o2h discovery and Co-Founder - o2h group

Prashant is a serial entrepreneur in life sciences and tech in which one of those companies was acquired by a public company. He is currently active in seed investing (a portfolio of ~50 companies), product/IP development, services, and building lab/office infrastructure. The early career was with the Strategy group at Accenture. He has a BEng, an MSc, in which he worked on the Human Genome Program at the Sanger Centre, and an MPhil in Management from the Judge Institute. Prashant is also a General Partner in the o2h SEIS/EIS Human Health Funds.


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Sunil

Sunil Shah

CEO - o2h Ventures and Co-Founder - o2h discovery

Sunil's Biography

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Sunil Shah

CEO - o2h Ventures and Co-Founder - o2h discovery

A serial entrepreneur having begun a career in the Life Sciences team at PA Consulting group followed by co-founding two companies in the information technology and life sciences sector. The second of these companies, Oxygen Healthcare Ltd was acquired by Piramal Enterprises Ltd (BSE: PEL). Sunil co-founded o2h ventures which involves discovery services / collaborations, seeding drug discovery, academic in-licensing and biotechnology incubation. Sunil has a degree in Biochemistry and an MBA from Cambridge University


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Andy Morley

Andy Morley

Chief Scientific Officer

Andy's Biography

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Andy Morley

Chief Scientific Officer

Andy is a highly experienced and accomplished Medicinal Chemist with over 25 years of experience in major pharmaceutical companies such as Sanofi-Aventis and AstraZeneca. He has extensive experience across all phases of drug discovery and has played a key role in the development of five candidates that have reached clinical trials. Andy is a prolific author and inventor, with over 55 publications and patents to his name. Since 2013, he has been working full-time with o2h Limited, where he leads the scientific evaluation of investment opportunities and provides scientific support. He has also served as CSO for two early-stage collaborations within the o2h Ventures portfolio, demonstrating his ability to successfully guide drug discovery projects from concept to clinical development.


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David Davies - o2h

David Davies

Head of Medicinal Chemistry

David's Biography

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David Davies

Head of Medicinal Chemistry

David Davies has 25 years of experience in medicinal chemistry within the pharmaceutical industry with a focus on the antibacterial area (clavulanates, penicillinates, pseudomonates and bacterial topoisomerase inhibitors). He previously worked at GSK and currently holds a part-time academic position at University College London (UCL). He served as the Head of Medicinal Chemistry at Antabio for nearly a decade, specialising in antibacterial research, and has extensive experience managing chemistry projects in multiple countries including France, UK, India and China. He is the inventor of 40 patents and has authored 37 publications.


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o2h group launched revolutionary project management app for drug discovery

o2h group launched revolutionary project management app for drug discovery. The app’s full suite of project management tools is available exclusively to live project collaborators and a lighter version is open for researchers looking for a quote for the synthesis of small molecules.

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