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From Molecule to Kilo: Rethinking Chemistry’s Role in Preclinical Drug Discovery

Malken Bayrakdarian
Vice President – Drug Discovery, Sygnature Discovery

In preclinical drug discovery, chemistry is often seen as a series of transactions: design a compound, synthesize it, purify it, test it. But when timelines tighten and complexity increases, as they inevitably do, that modular view begins to break down.

Instead, companies are realizing that chemistry isn’t just a service, it’s a strategic enabler. And when integrated early and intelligently, it can transform the pace and predictability of a program.

But that integration is easier said than done.

The Hidden Costs of Fragmented Chemistry

For biotech and pharma teams under pressure to move fast, the biggest risks often aren’t in the science, they’re in the handoffs. Working across multiple vendors or loosely connected internal teams can lead to:

  • Gaps in knowledge that delay decision-making
  • Misaligned priorities between chemistry and biology
  • Purification bottlenecks that stall delivery
  • Lack of scalability, especially when a lead compound must suddenly move to preclinical supply

These frictions don’t just slow things down, they increase cost, risk, and the likelihood of having to rework what’s already been done.

What Integrated Chemistry Should Look Like

In an ideal world, a discovery program would flow seamlessly from early SAR exploration to preclinical candidate nomination, with chemistry at its core, connected to biology, DMPK, protein sciences, and informatics in real time.

A modern chemistry strategy should include:

  • Medicinal chemistry that’s tightly linked to emerging data
  • Process chemistry and analytical support ready to scale when needed
  • Purification tools that can adapt to the compound, not the other way around
  • High-throughput tools like parallel synthesis and DoE to explore more, faster
  • Built-in flexibility to pivot between small-scale discovery and kilo-scale delivery without delay

That’s not just operational efficiency, it’s a competitive advantage.

The Journey to Kilo: When Scale Starts to Matter

One of the key inflection points in any drug discovery project is the transition from exploratory chemistry to scale-up. It’s often where momentum is lost, not because of scientific failure, but because of lack of preparedness.

Phase-appropriate process development, smart purification strategies, and continuity between discovery and preclinical supply are essential to cross that gap smoothly. That doesn’t mean jumping to GMP before it’s necessary, but it does mean thinking ahead.

Purification: Often Overlooked, Often the Bottleneck

Few things frustrate a program more than knowing what needs to be made, but not being able to isolate it at the right purity, at the right scale, or in the right timeframe.

The ability to pivot between analytical HPLC, prep HPLC, and preparative SFC, with no equipment limitations, can make or break a program’s momentum. Especially when:

  • Chiral resolution is required
  • Multiple isomers must be separated in a single step
  • A compound fails elsewhere due to poor peak shape or scale-up limitations

A separation sciences strategy built for speed, flexibility, and precision can turn weeks of troubleshooting into a day’s work.

Reframing Chemistry as a Competitive Lever

More and more teams are recognizing that the value of chemistry isn’t just in the molecules, it’s in the choices it enables. When purification, process development, analytical chemistry, and design are aligned, drug discovery becomes more than a sprint, it becomes scalable.

Programs that succeed in today’s market are built on:

  • Early-stage chemistry aligned with late-stage thinking
  • High-quality data packages that are CDMO-transfer ready
  • Fast-turnaround answers from deeply embedded scientific teams

This isn’t about adding layers of complexity. It’s about reducing friction, and letting innovation move at the pace it was meant to.

Why This Matters

You’ve probably worked with a CRO, or multiple, where bottlenecks started to appear once complexity increased: a novel structure with tricky solubility, a late-stage scale-up need, a molecule that failed purification at a critical moment.

That’s where integrated chemistry, separation sciences, and scalability aren’t just differentiators, they’re project-savers.

Closing Thought: Building with the End in Mind

In drug discovery, we’re all trying to do the same thing: turn ideas into therapies, faster and more predictably. That requires chemistry that’s not just good, it’s built for your biology, your timelines, and your goals.

When chemistry teams are integrated, purification isn’t a bottleneck, and process development is built for what’s next, your molecule moves forward, without hesitation.
And that’s the kind of momentum that matters.

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