Drug Discovery Services

Our scientific team has a wide range of expertise in performing chemistries with varying
levels of complexity and is amply supported by the required technology driven infrastructure.

The drug discovery services team is conversant with

handling:
 Heterocycles

 Macrocyclic building blocks

 Organometallics

 Chiral chemistry

 Phosphonates

 Metal mediated transformations

 Stability studies

 fluorine and boron chemistry services

Also, we have a proven track record across the following

drug discovery technology classes:
 Natural Product Synthesis (isolation, identification & characterization)

 Solid Phase Peptide Synthesis

 Solution Phase Peptide Synthesis

 Nucleoside Synthesis

 Nucleotides Building Block Synthesis

 GalNAc Ligands Synthesis

 ADC Linker-conjugate Synthesis

 Carbohydrates Synthesis

 Azasugars Synthesis

 PEG-Lipid Synthesis
  Unnatural Amino Acid Synthesis

 PROTAC Synthesis Services

All the above chemistry classes can be executed in multiple batches from mg to kg scales.

We understand that tackling and delivering different modalities of chemistry, from

completely exploratory to previously reported/literature supported chemistry, demands
different approaches. However, the following parameters still remain the fundamental bases
to design our approach viz. structural aspects of the target compound(s), safety requirements,
scales of delivery, specifications, literature support, complexity, exploration, reagents &
catalysts involved, overall cost related aspects, etc.

In an order to devise the syntheses of completely exploratory and novel molecules, we come-
up with different schemes by drawing upon our previous experience and applying
speculations to different synthetic pathways. Then, we narrow down on the most plausible
scheme(s) considering the parameters like the number of steps, required scales of delivery,
reactivity, yields and overall economy, etc. Once we have the most suitable route identified
we execute the scheme in a stepwise manner by monitoring the reaction variables &
conditions.

For the more exploratory projects we also recommend a short feasibility study to ascertain a
proof of concept before executing things at a larger scale. Alternatively, the molecules with
already established synthetic routes & available protocols move to a more delivery-focused
approach. Here the stepwise and overall cost and time efficiency get the major focus with the
help of tools like Reaxys and SciFinder, to explore the data on chemical reactions and other
literature. If the project demands optimization for a larger scale we also perform a small
feasibility study, mostly in parallel, at a smaller scale, and then a subsequent scale-up
considering the most preferred route. In terms of scaling up our efforts we have historically
conducted scale-ups from mg to multiple batches of kg scale for a final delivery of up to tens
of kgs under custom synthesis.

To ascertain our progress and avoid any wasteful reactions, we perform regular NMR and
LCMS checks at each step to gather and correlate the expected and real time stability data.
Finally, the chemists work closely to make sure that final compound(s) meet or exceed the
purity specification and get custom weighed in preferred vials. These compounds can then be
stored under controlled conditions or shipped, based on their order of priority, to any
particular or multiple locations anywhere across the globe.

In terms of operational aspects, we dedicate a team to each individual project with a typical
PhD to MSc ratio of 1:5 and with each of them having several years of relevant industrial
experience. These resources working on-bench are considered as billable resources. This
team works under the guidance of a project manager who oversees the daily activities of his
respective team(s). Furthermore, a project manager is helped by a project lead, who also
happens to be the single point of contact for the clients for all the written and
telecommunications. Each project lead monitors and provides his technical, non-technical,
and managerial inputs for the smooth functioning of his projects. The Project managers and
project leads remain non-billable resources for each collaboration. However, if desired,
bigger collaborations do get the option to have dedicated project managers and project leads
depending on their requirements and the size of the collaborations. We also conduct periodic
reviews and team meetings, of each team, with the site-head to make sure that the
communication flow is optimal from bottom-to-top and vice-versa.

Each project specific core synthetic chemistry team is very well supported by the cross
functional teams like analytical chemistry, program management, and supply chain
management. In addition to this, we also expose and train all our scientists on multiple
methodologies and across multiple business models to broaden their perspective and purview
of delivery shall there be a need.

Since this team works in a very close collaboration with the supply chain management team
we maintain a dynamic database of preferred vendors for project specific starting materials
and consumables. This vendor qualification is done considering the guidelines laid down by
the QA team, their past track records, economy and delivery turnaround times, etc. We also
utilize smart tools like SmartChem to segregate vendors details and shortlist the right ones
quickly. Furthermore, we also have a readily available centralized inventory of the most used
chemicals and reagents in-house.

Having and building a portfolio of scientific platforms we also have a technology-based

division of teams for the scientific platforms we have in place. Our decorated Scientific
Advisory Board (SAB) conducts remote and in-person periodic trainings across their areas of
expertise, training their respective teams working on novel applications of these platforms.
The SAB also tracks progress, addresses the technology specific challenges and trains the
team on recent advancements, etc. To take an example our photo and electrochemistry teams
work on generating some novel building blocks and libraries which are not possible through
conventional chemistry approaches.

Key Aspects
 Regular project health monitoring (PHM), fortnightly, for tracking the progress, gap
analysis, and value addition.

 Pre-defined client driven productivity metrics.

 In-house developed tools for tracking Raw material usage and sourcing.

 Dedicated flash chromatography and ELSD for lab scale purification for each lab-
REVELERIS® and combiflash purification systems.

 Collaboration specific dedicated report writing areas with restricted access.

 Monowave systems for small scale microwave synthesis and lyophilizers for freeze drying.

 ELN support: CDD, Scilligence, Signals by PE, Arxspan, Etc.

 Reaxys, and SciFinder access for all chemists.

 Secure e-rooms for data sharing- SharePoint and ShareFile.

 Restricted entry To synthetic chemistry, And analytical Labs.

Drug Development Services (Starting Material,
Intermediate & APIs) | CDMO Services

Contract research, development, and

manufacturing services organization (CDMO)
Chemveda’s CDMO (API, Starting Material and Intermediate development and
manufacturing) business division covers the following departments:

 Process R&D services

 Custom chemical development services
 DoE, QbD and process safety hazard assessment
 GMP manufacturing services
 Analytical development services
 Stability studies
 Regulatory support

In terms of deliveries, CDMO covers the following modalities from gram-scale

synthesis To multi-kilogram scale manufacturing:

 Pre-clinical, early phase, and late phase clinical development

 Regulatory starting materials (RSMs)

 Starting material development and Manufacturing

 Intermediate development & manufacturing

 New Chemical Entities (NCEs) and Active Pharmaceutical Ingredients (APIs)

 GalNAc Ligands (route scouting, selection & scaleup)

Process R&D Services

At Chemveda Lifesciences, the process development group adopts a delivery-
oriented, risk-based approach to make critical decisions right from route scout to
process development, and then manufacturing. The key principles that outline each
project here are: accuracy, efficiency, and speed. The overall team is comprised of
chemists, engineers, and process analysts with expertise in every phase of process
research.

The team works in coherence with all the other cross functional teams like process
development scientists, analytical development, EHS, commercial sourcing, quality
assurance and tech-transfer, etc. to ensure an on-time in full delivery.

We are equipped to follow both traditional and enhanced approaches by using ICH
Q9 & 11 guidelines and implement QbD elements for finding the best operational
ranges, wherever necessary. The team has expertise in solid state chemistry where
we diligently optimize the process for the desired polymorph and particle size. Also,
the team is well-versed with diversified requirements of phase I, II, and III, involving
both scientific and regulatory aspects.

Our critical assessment for the selection of the most suitable route suitable for
commercial manufacturing is based on the following MUST criteria:

 No column purifications

 No safety barriers

 IP, and regulatory implications

 Improving the cost efficiency,

 Commercial availability of raw materials and confidence in supply of materials at

large scales
 Scalability of the process, etc.

Process R&D capabilities

 Synthetic route development/route scouting

 Process development, optimization and verification

 Process hazard analysis/process safety assessment

 Pilot scale development (based on requirement)

 Technology transfer and scale-up

 Polymorph, salt, and hydrate screening

 Particle size development, and optimization

 Metabolite and impurity synthesis

 N-Acetylgalactosamine (GalNAc) oligonucleotide conjugate synthesis

 Analytical method development, and validation

 Analytical method verification, and transfer

 Stability studies, and storage

 Forced degradation studies

 Impurities identification, isolation, and characterization

 Reference and working standards qualification

 Elemental/metal analysis

Route Scouting Services

In pre-clinical development, often, the speed of delivery takes precedence over
having an optimal synthetic route. However, while taking the project to the clinic an
alternative synthetic route is required to deal with safety challenges and improving
cost efficiency. Hence, Chemveda performs route scouting and route comparison
studies to come up with more efficient synthetic route(s) involving reduced number of
process steps, less expensive raw materials, safety aspects, etc. This is followed by
route familiarization studies to identify the most appropriate one considering the
delivery timelines and costs involved. We also specialize in route scouting of N-
Acetylgalactosamine (GalNAc) ligands for oligonucleotide conjugates.
Analytical Development Services
Chemveda’s analytical development team and process scientists have a seamless
co-ordination in terms of devising analytical methods to support the development of
intermediates, and drug substances. The team also routinely performs method
validations, stability testing of intermediates, and drug substances.
Technology Transfer Services
Our experienced Technology Absorption & Transfer Team (TATT) undertakes
transfer of technology from R&D to manufacturing site or from your organization to
Chemveda. The team has a proven track record of successfully taking lab processes
to the manufacturing plant and deliver required quantity of chemical substances with
desired specifications and within agreed delivery timelines.
 Custom Chemical Development and Manufacturing Services
We have an ably equipped kilo lab facility suitable to deliver multiple batches of up to
kilogram scale under GMP/non-GMP conditions.
Kilo-Lab
Chemveda’s fully-equipped kilo-lab allows for rapid scale-ups, and development of
scalable & robust chemical processes using advanced process methodologies to
provide a quick supply of starting material, intermediate and API in the early phase of
the development
Key Aspects:
 First scale-up out of laboratory

 Rapid scale-up to support client’s initial drug testing, i.e. pre-clinical studies or sometimes
phase-I of clinical trials

 Kilo gram scale deliveries

 Developing knowledge on process, and mini-piloting

 Scale-down studies to explore process changes

 Demo batches for process simulation studies

 Synthesis of quantities usually ranging from ~500g to under 10 kg

GLP API, Starting Material & Intermediate

Capabilities

Chemveda’s GLP facility is equipped to deliver drug substances such as API, starting material
and intermediate from gram to few kg scales intended for non-clinical laboratory studies
and regulatory submissions. The synthesis capabilities are designed to operate in the
range of -80 °C to 200 °C and all the resulting samples are then analysed in a DCGI-CDSCO
(Drugs Controller General of India-Central Drugs Standard Control Organisation) certified
QC lab and released after the final review of QA.

To give this facility a wider range in terms of its purification capabilities it has also been
complemented with a standalone 150L MPLC (Medium Pressure Flash Liquid
Chromatography) instrument. The key utility here is to purify less pure and overly bulky
chemical substances under safe, medium pressure conditions at a faster pace.

In addition to this, Chemveda also supports its collaborators with eCTD ready CMC
documentation required for IND filing.
 Presentation related

Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory

drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic.[9]

Aspirin is also used long-term to help prevent further heart attacks, ischaemic strokes, and blood
clots in people at high risk.[9] For pain or fever, effects typically begin within 30 minutes. [9] Aspirin
works similarly to other NSAIDs but also suppresses the normal functioning of platelets.[9]

Mechanism of action
Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to
its irreversible inactivation of the cyclooxygenase (COX; officially known as prostaglandin-
endoperoxide synthase, PTGS) enzyme required for prostaglandin and thromboxane
synthesis.

Aspirin acts as an acetylating agent where an acetyl group is covalently attached to

a serine residue in the active site of the PTGS enzyme (Suicide inhibition). This makes
aspirin different from other NSAIDs (such as diclofenac and ibuprofen), which are
reversible inhibitors.

Trade name Aspirin (Bayer)

Drug class Nonsteroidal anti-inflammatory drug (NSAID)

Route of administration Oral, rectal

Bioavailability 80-100%

Protein binding 80-90%

Metabolism Liver (CYP2C19 and possibly CYP3A), some is also

hydrolysed to salicylate in the gut wall

Elimination half life Dose-dependent; 2–3 h for low doses (100 mg or less), 15–30 h for
larger doses.

Excretion Urine (80–100%), sweat, saliva, feces

Mechanism of action Mainly irreversible inactivation of cyclooxygenase

enzymes (COX-1 & COX-2)
 Aciclovir (ACV), also known as acyclovir,

Aciclovir (ACV), also known as acyclovir,[3] is an antiviral medication.[4] It is primarily used

for the treatment of herpes simplex virus infections, chickenpox, and shingles.[5] Other uses
include prevention of cytomegalovirus infections following transplant and severe
complications of Epstein–Barr virus infection.[5][6] It can be taken by mouth, applied as a
cream, or injected.[5

Mechanism of action:

Aciclovir is converted by viral thymidine kinase to aciclovir monophosphate, which is then

converted by host cell kinases to aciclovir triphosphate (ACV-TP, also known as aciclo-
GTP).[28] ACV-TP is a very potent inhibitor of viral DNA replication. ACV-TP competitively
inhibits and inactivates the viral DNA polymerase.[41] Its monophosphate form also
incorporates into the viral DNA, resulting in chain termination

Trade name Zovirax, others

Drug class Antiviral

Route of administration Intravenous, by mouth, topical, eye ointment

Bioavailability 15–20% (by mouth)

Protein binding 9–33%[

Metabolism Liver

Elimination half life 2–4 hours

Excretion Kidney (62–90% as unchanged drug)

Mechanism of action inhibitor of viral DNA replication. ACV-TP competitively

inhibits and inactivates the viral DNA polymerase
Zidovudine
Zidovudine (ZDV), also known as azidothymidine (AZT), was the first antiretroviral
medication used to prevent and treat HIV/AIDS. It is generally recommended for use in
combination with other antiretrovirals.[6] It may be used to prevent mother-to-child spread
during birth or after a needlestick injury or other potential exposure.[6] It is sold both by itself
and together as lamivudine/zidovudine and abacavir/lamivudine/zidovudine.[6] It can be used
by mouth or by slow injection into a vein

Mechanism of action:
AZT is a thymidine analogue. AZT works by selectively inhibiting HIV's reverse transcriptase,
the enzyme that the virus uses to make a DNA copy of its RNA. Reverse transcription is
necessary for production of HIV's double-stranded DNA, which would be subsequently integrated
into the genetic material of the infected cell (where it is called a provirus).[40][41][42]

Cellular enzymes convert AZT into the effective 5'-triphosphate form. Studies have shown that
the termination of HIV's forming DNA chains is the specific factor in the inhibitory effect. [43]

At very high doses, AZT's triphosphate form may also inhibit DNA polymerase used by human
cells to undergo cell division, but regardless of dosage AZT has an approximately 100-fold
greater affinity for HIV's reverse transcriptase.[44] The selectivity has been suggested to be due to
the cell's ability to quickly repair its own DNA chain if it is disrupted by AZT during its formation,
whereas the HIV virus lacks that ability.[45] Thus AZT inhibits HIV replication without affecting the
function of uninfected cells.[40] At sufficiently high dosages, AZT begins to inhibit the cellular DNA
polymerase used by mitochondria to replicate, accounting for its potentially toxic but reversible
effects on cardiac and skeletal muscles, causing myositis.[46][47][48][49][50]

Trade name Retrovir, others

Drug class Anti HIV

Route of administration By mouth, intravenous, rectal suppository

Bioavailability Complete absorption, following first-pass metabolism systemic

availability 75% (range 52 to 75%)

Protein binding 30 to 38%

Metabolism Liver

Elimination half life 0.5 to 3 hours

Excretion Kidney and Bile duct

Mechanism of action Inhibiting HIV's reverse transcriptase, the enzyme that the
virus uses to make a DNA copy of its RNA.
Ranitidine

Ranitidine, sold under the brand name Zantac among others, is a medication used to
decrease stomach acid production.[12] It is commonly used in treatment of peptic ulcer
disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome

In September 2019, the probable carcinogen N-nitrosodimethylamine (NDMA) was discovered in

ranitidine products from a number of manufacturers, resulting in recalls. [14][15][16][17]

In April 2020, ranitidine was withdrawn from the United States market and suspended in the
European Union and Australia due to these concerns.[18][19][20][11][21][22]

In 2022, these concerns were confirmed in a nationwide[which?] population study "ranitidine

increased the risk of liver", lung, gastric and pancreatic cancer by 22%,17%, 26% and 35%,
respectively.[23] It increased overall cancer risk 10%, p < 0.001.[2

Mechanism of action[edit]
Ranitidine is a competitive, reversible inhibitor of the action of histamine at the histamine
H2 receptors found in gastric parietal cells. This results in decreased gastric acid secretion and
gastric volume, and reduced hydrogen ion concentration.[122] Ranitidine's acid-lowering effect is
more pronounced for basal and nocturnal acid secretion than it is for food-stimulated acid
secretion. Additional indirect effects of ranitidine are decreased pepsin secretion and increased
nitrate-reducing bacterial flora

Trade name Zantac,[1] others

Drug class Histamine H2 receptor antagonist, aka H2 blocker[1]

Route of administration By mouth, intravenous (IV)

Bioavailability 50% (by mouth)

Protein binding 15%

Metabolism Liver: FMOs, including FMO3; other enzymes

 Elimination half life 2–3 hours

Excretion 30–70% kidney

Mechanism of action competitive, reversible inhibitor of the action of histamine

at the histamine H2 receptors found in gastric parietal
cells.

Prazosin

Prazosin, sold under the brand name Minipress among others, is a medication used to
treat high blood pressure, symptoms of an enlarged prostate, and nightmares related to post-
traumatic stress disorder (PTSD).[6] It is an α1 blocker.[6] It is a less preferred treatment of high
blood pressure.[6] Other uses may include heart failure and Raynaud syndrome.[7] It is taken by
mouth.[6]

Common side effects include dizziness, sleepiness, nausea, and heart palpitations.[6] Serious
side effects may include low blood pressure with standing and depression.[6][7] Prazosin is a non-
selective inverse agonist of the α1-adrenergic receptors.[6] It works to decrease blood pressure by
dilating blood vessels and helps with an enlarged prostate by relaxing the outflow of the bladder.
[6]
How it works in PTSD is not entirely clear.[6]

Prazosin was patented in 1965 and came into medical use in 1974.[8] It is available as a generic
medication.[6] In 2020, it was the 190th most commonly prescribed medication in the United
States, with more than 2 million prescriptions.[

Trade name Minipress, others

Drug class α1 blocker

Route of administration By mouth

Bioavailability ~60%

Protein binding 97%

Metabolism -

Elimination half life 2–3 hours

 Excretion -

Mechanism of action Prazosin is an α1-blocker that acts as a non-

selective inverse agonist at α1-adrenergic receptors

Anastrozole

Anastrozole, sold under the brand name Arimidex among others, is

an antiestrogenic medication used in addition to other treatments for breast cancer.[6]
[7]
Specifically it is used for hormone receptor-positive breast cancer.[7] It has also been used to
prevent breast cancer in those at high risk.[7] It is taken by mouth.[7]

Trade name Arimidex, Aremed, others[

Drug class Aromatase inhibitor; Antiestrogen

Route of administration By mouth

Bioavailability Unknown (but well-absorbed in animals

Protein binding 40%

Metabolism Liver (~85%) (N-dealkylation, hydroxylation, glucuronidation

Elimination half life 4--50 hours

Excretion Urine (11%

Mechanism of action Anastrozole works by reversibly binding to

the aromatase enzyme, and through competitive
inhibition blocks the conversion
of androgens to estrogens in peripheral
(extragonadal) tissues
Methotrexate
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy
agent and immune-system suppressant.[4] It is used to treat cancer, autoimmune diseases,
and ectopic pregnancies.[4] Types of cancers it is used for include breast
cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease,
and osteosarcoma. Types
[4]
of autoimmune diseases it is used for
include psoriasis, rheumatoid arthritis, and Crohn's disease.[4] It can be given by mouth or
by injection.[

Trade name Trexall, Rheumatrex, Otrexup, others[

Drug class -

Route of administration By mouth, intravenous (IV), intramuscular (IM), subcutaneous

injection (SC), intrathecal

Bioavailability 60% at lower doses, less at higher doses

Protein binding 35–50% (parent drug),[6] 91–93% (7-hydroxymethotrexate)[

Metabolism Hepatic and intracellular[6]

Elimination half life 3–10 hours (lower doses), 8–15 hours (higher doses

Excretion Urine (80–100%), feces (small amounts)

Mechanism of action Anastrozole works by reversibly binding to

the aromatase enzyme, and through competitive
inhibition blocks the conversion
of androgens to estrogens in peripheral
(extragonadal) tissues
Trovafloxacin

Trovafloxacin (sold as Trovan by Pfizer and Turvel by Laboratorios Almirall) is a broad

spectrum antibiotic that inhibits the uncoiling of supercoiled DNA in various bacteria by
blocking the activity of DNA gyrase and topoisomerase IV.[1] It was withdrawn from the market
due to the risk of hepatotoxicity. It had better Gram-positive bacterial coverage but less Gram-
negative coverage than the previous fluoroquinolones.

Trovafloxacin use is significantly restricted due to its high potential for inducing serious and
sometimes fatal liver damage.[2] Currently, the drug is not approved for use in the U.S. or the
European Union due to association with cases of acute liver failure and death.

Trade name Trexall, Rheumatrex, Otrexup, others[

Drug class Antibacterial agent

Route of administration Oral, intravenous

Bioavailability ~88%

Protein binding ~76%

Metabolism Metabolism Trovafloxacin is metabolized by

conjugation (the role of cytochrome P450 oxidative
metabolism of trovafloxacin is minimal). The major
metabolites include the ester glucuronide, which
appears in the urine (13% of the administered dose);
and the N -acetyl metabolite, which appears in the
feces and serum (9% and 2.5% of the administered
dose, respectively). Other minor metabolites include
diacid, hydroxycarboxylic acid, and sulfamate, which
 have been identified in both the feces and the urine in
small amounts (< 4% of the administered dose)

Elimination half life 9.1 h to 12.2 h (dose 100 to 200 mg tablets). Following
intravenous infusion, half-life ranged from 9.4 to 12.7
hours over a dosage range of 100 to 300 mg.

Excretion Approximately 50% of an oral dose is excreted

unchanged (43% in the feces and 6% in the urine).

Mechanism of action Trovafloxacin is a fluoronaphthyridone related to the

fluoroquinolones with in vitro activity against a wide
range of gram-negative and gram-positive aerobic and
anaerobic microorganisms. The bactericidal action of
trovafloxacin results from inhibition of DNA gyrase and
topoisomerase IV. DNA gyrase is an essential enzyme
that is involved in the replication, transcription, and repair
of bacterial DNA. Topoisomerase IV is an enzyme known
to play a key role in the partitioning of the chromosomal
DNA during bacterial cell division.

Potassium iodide - light brown

Lead iodide - yellow
Zinc sulphate - white
Barium sulphate - white colour
Ferrous sulphate - green
Copper sulphate - blue
Copper nitrate - blue
Copper chloride - blue green
Zinc sulphate - colourless
Silver chloride - white
Copper hydroxide - green