Services

Chemistry Services

The challenges of chemical synthesis are always motivational for team Intonation. Our growing team of chemists are supported by automation, modern infrastructure and matching analytical capabilities for high productivity.
The highly experienced medicinal chemistry team at intonation is capable of designing and executing elegantly complex chemical transformations expeditiously. Our chemistry services include –

Synthetic Chemistry

We have a long and successful track record of developing synthetic routes and executing efficient and cost effective synthesis from milligram to kilogram quantities. Our expertise in Linker chemistry has enabled us to develop a broad library of building blocks for quick synthesis of difficult PROTACs in 100-500 milligram quantities.

Our capabilities includes:

  • heterocyclics
  • Macrocycles
  • Peptides
  • Carbohydrates
  • nucleosides
  • PROTACs
  • chiral ligand
  • auxiliary based asymmetric synthesis

 

In addition we also support the synthesis of the following :
Building blocks, Reference standards, impurities, intermediates, metabolities.

Medicinal Chemistry

Our highly experienced medicinal chemistry team is credited with sixteen INDs and six marketed drugs. We leverage our team’s experience of 200 plus years in multiple therapeutic areas including Oncology, Inflammation, Infection, CNS, etc, to efficiently support medicinal chemistry projects; including hit-to-lead, lead optimization and preclinical development.

Specific services include:

  • Lead identification and optimization: design and synthesis of the latest analogues to optimize potency, selectivity, efficacy, bioavailability, metabolism, etc.
  • Hit confirmation and expansion (confirm structure and activity of hit clusters). Synthesis of selected analogues to gauge scaffolds and choose lead series
  • Small molecule patent strategy development and implementation (done together with a law firm)
  • Project management and consulting
  • Generate proprietary structures (knowledge-based design)
  • Optimization of scaffolds to resolve different ADME issues
  • Design and synthesis of a focussed library to deal with selected medicinal chemistry issues
Computational Chemistry

We have dedicated computational chemists, who are well-versed with the latest software and algorithms to work in close collaboration with our team of medicinal chemists. They carry out target analysis, library design, virtual screening, ligand and protein structure-based discovery. In addition to our in-house databases, we are amenable to utilize online resources to advance discovery projects. Our cloud server enables real time sharing of large data files.

We provide the following services:

  • Manually curated and proprietary virtual library of 10 million lead like molecules.
  • Support compound procurement and analog by catalog efforts
  • Virtual ligand screening utilizing water mapping and energetics
  • Docking and scoring of compounds in protein structure
  • Development of Homology model
  • Multi-Parameter Optimization (MPO or MPOv2) calculation
Analytical Chemistry

Our analytical chemistry team is composed of experienced chemists with diverse skill sets ranging from chiral separation to molecular characterization by NMR studies including NOSEY, COSEY, HR-NMR, 2D-NMR, and IR, etc. They are supported with a fully equipped analytical laboratory. We have a dedicated QC team for the final release of the client’s compounds.

We offer the following services:

  • Analytical HPLC method development
  • Purification of chiral and achiral compounds (up to g scale) by Prep-HPLC
  • LCMS and HPLC purity analysis (Both chiral and achiral compounds)
High Throughput Chemistry
We have developed automated platforms, processes and reagent procurement for parallel synthesis to effectively and economically synthesise and manage libraries to support hit finding. We have library management tools and can provide compounds barcoded in multiple formats as required by our clients.

Pharmacology Services

Our pharmacology team’s principal role is to support structure-activity relationships to advance the discovery programs. Our bioscience knowledge of target biology, therapeutic area specialization, and ability to work collaboratively at each stage of the drug discovery process allows the efficient design or transfer and validation of high-quality single assays or cascades to accelerate your hit finding, hit-to-lead and lead optimization programs. We have the expertise and infrastructure to support biochemical, cell-based and radio-ligand binding assays.
Biochemical Enzyme Assays

With an in-depth knowledge in enzymology, our team is capable of designing complex enzyme assays to study kinetic parameters. We have a broad toolbox of assay readouts that we will design or we can transfer and validate clients’ assays to support a fully integrated program.

Formats: homogenous and non-homogenous

Readouts:

  • Radiolabelled
  • Fluorescent
  • Colorimetric
  • Luminescent
  • Fluorescence polarization (FP)
  • Alpha screen

Substrate identification and optimization Assay parameters :

  • Signal: background ratio (S/B)
  • Assay Linearity, substrate Km, Vmax
  • Turnover, reagent stability, pH, salt, detergent effect, reducer optimization, uniformity using multi-drop, etc.

Experience in broad classes of enzymes includes :

  • Inhibition assays: Determination IC50, Ki, Kd
  • Protein-protein interactions
  • We can support both 96 well and 384 well formats
Radio Isotope Facility

A dedicated Type-II radioactive facility is established to handle UNSEALED RADIOISOTOPES. The radioactive lab is provided to handle 3H, 32P, 14C, 35S. This facility works under the supervision of a dedicated Radiation safety officer (RSO). The facility was designed and constructed as per the AERB guidelines.

In Vitro/In-Vivo ADME

At Intonation, we carry out in-vitro and in in-vivo pharmacologic and physicochemical property analysis of biologically active small molecules to support drug discovery projects. We feature the assessment and optimization of Structure-Pharmacological / Property-Relationships (SPR), which may be a critical step for efficacy evaluation.

Additionally, to assess compound characteristics like solubility, protein binding, permeability, stability etc. our teams prioritize different structural classes and order them not only on potency but also in reference to potential downstream absorption or metabolic liabilities.

In-vitro – Physico-chemical characterization, cell and non-cell-based absorption, metabolism (microsomes/hepatocytes), CYP isozymes.

In-vitro ADME Screening

Aqueous Solubility: Kinetic, Thermodynamic, Thermodynamic equilibrium solubility in water, organic solvents, buffers, formulations solvents.

Lipophilicity: LogP/LogD

Metabolic Stability: Rat, mouse, dog, human microsomes, Cryopreserved hepatocytes

Drug-drug interaction: CYP450 inhibition or CYP450 induction

Distribution: Plasma protein binding, Blood partitioning, PAMPA/Caco-2 permeation studies

Plasma stability and Plasma Protein binding: (Mouse, Rat, Dog and Human), Stability in SGF and SIF

CYP Inhibition (1A2, 2C8, 2C9, 2C19, 2D6, 3A4): both % inhibition and IC50, Time-dependent CYP inhibition

In-life Pharmacokinetics

Bioavailability, blood-brain barrier, cerebrospinal fluid, tissue distribution, etc. in rodents. Our In-vivo services include exploratory PK, PD and TK studies. Understanding the bioavailability, exposure, half-life, clearance and metabolism of a drug may be the difference between success and failure in the clinic. We provide in vivo dosing and sampling in rodents, PK bioanalysis, and report preparation.

  • Routes of Administration – Oral (PO), Subcutaneous (SC), Intravenous (IV), Intramuscular (IM), Intraperitoneal (IP), Dermal
  • Multiple Dosing regimen- Single/Multi Dose and IV cassette PK in mouse and rat
  • Collection from – Whole blood serum, plasma, urine, faeces and tissue (including the brain)
  • Delivery Timelines – Initial results from PK studies will be available in 3-5 days and data will be posted in our secure web portal for immediate client access.
Bioanalytical Lab Services
  • Pharmacokinetics (PK) Studies, PK Sample Analysis, Toxicokinetics (TK) Studies, Rapid PK Screening, Mass Balance, Tissue Distribution, Bioequivalence (formulation support), MSD-ECLA (Meso Scale Discovery) Assays, ELISA Assays
  • Metabolite ID and kinetic studies- including metal bowl studies, radiolabel studies: 14C, 3H and 125I

Integrated Drug Discovery Solutions

Researchers at Intonation possess not only specialized knowledge of a specific field but a broad translational knowledge of all fields, demonstrating that true integration results in the invention of strong drug candidates. This is how our chemists, biologists and computational scientists have worked together for nearly a decade.

Effective drug discovery campaigns are executed by multi-disciplinary, tight-knit teams working in close communication, reviewing data in real-time and continuously adjusting to events and conditions to overcome obstacles.

At Intonation, drug discovery occurs during a cycle of biology, chemistry, structural biology and in silico modelling, during which re-evaluations and readjustments happen seamlessly and in real-time. Our integrated approach combines the experience of our scientists, the agility of our teams, and therefore the transparency of our communications to supply a turnkey solution for your most challenging programs.
We offer all the relevant capabilities required to support drug discovery projects from hit identification through to candidate selection and beyond. We also offer service bundles or fully integrated drug discovery support to our clients, your partners and advisors, by blending extensive drug discovery knowledge, expert project management and excellent understanding and domain knowledge of therapeutic areas, particularly oncology, pain and anti-infectives.

  • World Class science and project management
  • Critical mass and optimised processes
  • Therapeutic area domain knowledge
  • State-of-the-art infrastructure
  • Diary of success delivering integrated projects
In-vitro ADME Screening

Aqueous Solubility: Kinetic, Thermodynamic, Thermodynamic equilibrium solubility in water, organic solvents, buffers, formulations solvents.

Lipophilicity: LogP/LogD

Metabolic Stability: Rat, mouse, dog, human microsomes, Cryopreserved hepatocytes

Drug-drug interaction: CYP450 inhibition or CYP450 induction

Distribution: Plasma protein binding, Blood partitioning, PAMPA/Caco-2 permeation studies

Plasma stability and Plasma Protein binding: (Mouse, Rat, Dog and Human), Stability in SGF and SIF

CYP Inhibition (1A2, 2C8, 2C9, 2C19, 2D6, 3A4): both % inhibition and IC50, Time-dependent CYP inhibition

In-life Pharmacokinetics

Bioavailability, blood-brain barrier, cerebrospinal fluid, tissue distribution, etc. in rodents. Our In-vivo services include exploratory PK, PD and TK studies. Understanding the bioavailability, exposure, half-life, clearance and metabolism of a drug may be the difference between success and failure in the clinic. We provide in vivo dosing and sampling in rodents, PK bioanalysis, and report preparation.

  • Routes of Administration – Oral (PO), Subcutaneous (SC), Intravenous (IV), Intramuscular (IM), Intraperitoneal (IP), Dermal
  • Multiple Dosing regimen- Single/Multi Dose and IV cassette PK in mouse and rat
  • Collection from – Whole blood serum, plasma, urine, faeces and tissue (including the brain)
  • Delivery Timelines – Initial results from PK studies will be available in 3-5 days and data will be posted in our secure web portal for immediate client access.
Bioanalytical Lab Services
  • Pharmacokinetics (PK) Studies, PK Sample Analysis, Toxicokinetics (TK) Studies, Rapid PK Screening, Mass Balance, Tissue Distribution, Bioequivalence (formulation support), MSD-ECLA (Meso Scale Discovery) Assays, ELISA Assays
  • Metabolite ID and kinetic studies- including metal bowl studies, radiolabel studies: 14C, 3H and 125I

Chemistry Services

The challenges of chemical synthesis are always motivational for team Intonation. Our growing team of chemists are supported by automation, modern infrastructure and matching analytical capabilities for high productivity.
The highly experienced medicinal chemistry team at intonation is capable of designing and executing elegantly complex chemical transformations expeditiously. Our chemistry services include –

Synthetic Chemistry

We have a long and successful track record of developing synthetic routes and executing efficient and cost effective synthesis from milligram to kilogram quantities. Our expertise in Linker chemistry has enabled us to develop a broad library of building blocks for quick synthesis of difficult PROTACs in 100-500 milligram quantities.

Our capabilities includes:

  • heterocyclics
  • Macrocycles
  • Peptides
  • Carbohydrates
  • nucleosides
  • PROTACs
  • chiral ligand
  • auxiliary based asymmetric synthesis

 

In addition we also support the synthesis of the following :
Building blocks, Reference standards, impurities, intermediates, metabolities.

Medicinal Chemistry

Our highly experienced medicinal chemistry team is credited with sixteen INDs and six marketed drugs. We leverage our team’s experience of 200 plus years in multiple therapeutic areas including Oncology, Inflammation, Infection, CNS, etc, to efficiently support medicinal chemistry projects; including hit-to-lead, lead optimization and preclinical development.

Specific services include:

  • Lead identification and optimization: design and synthesis of the latest analogues to optimize potency, selectivity, efficacy, bioavailability, metabolism, etc.
  • Hit confirmation and expansion (confirm structure and activity of hit clusters). Synthesis of selected analogues to gauge scaffolds and choose lead series
  • Small molecule patent strategy development and implementation (done together with a law firm)
  • Project management and consulting
  • Generate proprietary structures (knowledge-based design)
  • Optimization of scaffolds to resolve different ADME issues
  • Design and synthesis of a focussed library to deal with selected medicinal chemistry issues
Computational Chemistry

We have dedicated computational chemists, who are well-versed with the latest software and algorithms to work in close collaboration with our team of medicinal chemists. They carry out target analysis, library design, virtual screening, ligand and protein structure-based discovery. In addition to our in-house databases, we are amenable to utilize online resources to advance discovery projects. Our cloud server enables real time sharing of large data files.

We provide the following services:

  • Manually curated and proprietary virtual library of 10 million lead like molecules.
  • Support compound procurement and analog by catalog efforts
  • Virtual ligand screening utilizing water mapping and energetics
  • Docking and scoring of compounds in protein structure
  • Development of Homology model
  • Multi-Parameter Optimization (MPO or MPOv2) calculation
Analytical Chemistry

Our analytical chemistry team is composed of experienced chemists with diverse skill sets ranging from chiral separation to molecular characterization by NMR studies including NOSEY, COSEY, HR-NMR, 2D-NMR, and IR, etc. They are supported with a fully equipped analytical laboratory. We have a dedicated QC team for the final release of the client’s compounds.

We offer the following services:

  • Analytical HPLC method development
  • Purification of chiral and achiral compounds (up to g scale) by Prep-HPLC
  • LCMS and HPLC purity analysis (Both chiral and achiral compounds)
High Throughput Chemistry
We have developed automated platforms, processes and reagent procurement for parallel synthesis to effectively and economically synthesise and manage libraries to support hit finding. We have library management tools and can provide compounds barcoded in multiple formats as required by our clients.