Solving serotonin-dependent diseases: next-generation TPH1 inhibitors

Our technology

 

Novel class of TPH1 inhibitors

  • Binding to the Trp (substrate) and BH4 (co-factor) binding pockets of TPH1 simultaneously.

  • Potent inhibition of 5-HT production in vitro and in vivo.

 

TRYPTO THERAPEUTICS is developing a set of novel, proprietary small molecules at TRL level 4 to treat serotonin-related diseases.

We have developed and patented a novel class of TPH inhibitors (TPHi) with nanomolar potency in vitro.

Our TPHi differ in their scaffold, binding mode, and potency from TPHi that are currently on the market or under clinical investigation.

The lead TPHi compound achieved readiness to transition from academic research towards a targeted pharmaceutical development.

Comprehensive data package:

  • Potency & selectivity in vitro

  • ADME / TOX in vitro

  • PK in vivo

  • PD in vivo

  • Safety and toxicity in vivo

Completed development milestones:

  • Suitable ADME / Tox

  • Oral PK profile

  • Reproduced Proof of Concept in PAH

  • CMC process established

  • Proof of Concept for CMC scalability

  • Strong IP protection

Target indications and pipelines focus

  • Oncology

    Pathologically high serotonin levels contribute to tumor growth and metastasis in Colorectal Cancer, as well as severe gastrointestinal and cardiac symptoms in NET tumor patients (Carcinoid Syndrome).

  • Pulmonary & cardiovascular disorders

    Increased peripheral serotonin levels contribute to pulmonary vessel remodeling and aggravate the disease progression in PAH and PH-LHD subtypes of pulmonary hypertension.

  • Explorative: inflammatory and fibrotic diseases

    Besides its pro-inflammatory function in Asthma and IBD, serotonin is pathogenetically relevant for different kinds of fibrotic diseases in the lungs, liver, skin, and kidneys.

  • Explorative: Obesity and metabolism

    Peripheral serotonin regulates metabolism, but might also contribute to local inflammatory processes and fibrotic changes in the liver.

Our key publications

  • TPT‐004, a Next‐Generation Inhibitor of Tryptophan Hydroxylase, Ameliorates Pulmonary Arterial Hypertension in Rats

    Journal of the American Heart Association

  • Novel Tryptophan Hydroxylase Inhibitor TPT-001 Reverses PAH, Vascular Remodeling, and Proliferative-Proinflammatory Gene Expression

    JACC: Basic to Translational Science

  • Structure-Based Design of Xanthine-Imidazopyridines and -Imidazothiazoles as Highly Potent and In Vivo Efficacious Tryptophan Hydroxylase Inhibitors

    Journal of Medicinal Chemistry

  • Structure-Based Design of Xanthine-Benzimidazole Derivatives as Novel and Potent Tryptophan Hydroxylase Inhibitors

    Journal of Medicinal Chemistry

  • Inhibition of serotonin synthesis: A novel therapeutic paradigm

    Pharmacology & Therapeutics

  • Peripheral Serotonin Synthesis as a New Drug Target

    Trends in Pharmacological Sciences

 Our small molecule technology reducing pathologically increased peripheral serotonin