Protirelin
[CAS 24305-27-9]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs >> Thyroid hormone and antithyroid drugs
• Name: Protirelin
• Synonyms: L-Pyroglutamyl-L-histidyl-L-prolinamide; Thyrotropin releasing hormone; (2S)-N-[(2S)-1-[(2S)-2-Carbamoylpyrrolidin-1-yl]-3-(1H-imidazol-2-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide
• Molecular Formula: C₁₆H₂₂N₆O₄
• Molecular Weight: 362.38
• Protein Sequence: XHP
• CAS Registry Number: 24305-27-9
• EC Number: 246-143-4
• SMILES: C1C[C@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@@H]3CCC(=O)N3)C(=O)N

Properties

• Density: 1.5±0.1 g/cm³ Calc.^*
• Boiling point: 942.1±65.0 °C 760 mmHg (Calc.)^*
• Flash point: 523.6±34.3 °C (Calc.)^*
• Index of refraction: 1.617 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H332
• Safety Statements: P261-P271-P304+P340-P317

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H332
Reproductive toxicity	Repr.	1B	H360

chemBlink Chemical Story

Protirelin is the synthetic form of thyrotropin-releasing hormone, often abbreviated TRH. Its structure is a tripeptide: pyroglutamyl, histidyl and proline amide. The end groups are important. The first residue has a cyclic pyroglutamyl group, and the last residue ends in a carboxamide. A list of three amino acid names alone would not specify the same molecule, because a peptide with different terminal groups has different chemistry.

Work in the late 1960s linked a hypothalamic signal to a defined structure. Studies of purified porcine thyrotropin-releasing hormone isolated material with measurable biological activity. Comparison with synthetic pyroglutamyl-histidyl-proline amide then allowed researchers to ask whether the proposed structure matched the natural substance in chemical and hormonal properties. The ability to synthesize a proposed structure made the structural assignment testable in a way that a description of activity alone could not.

The hormone's name describes a relay. TRH can stimulate release of thyrotropin, also known as thyroid-stimulating hormone or TSH, from the pituitary. TSH in turn acts on the thyroid. Thus protirelin and thyrotropin are distinct substances at different steps in the pathway; neither is simply another name for thyroid hormone. TRH can also stimulate prolactin release. A hormone's name usually reflects the activity that brought it to attention, not necessarily the complete range of its physiological effects.

A synthetic stimulus makes it possible to observe a timed response and ask where a system can or cannot respond. The timing and size of a measured response are evidence about the particular experiment, not a diagnosis on their own. The history of protirelin is notable because a signal that operates across organs could be linked to just three residues with a particular arrangement of end groups. That result helped turn a physiological idea about communication between the hypothalamus and pituitary into a question that could be investigated with a defined molecule.

References:
1. NLM MeSH. Protirelin, CAS 24305-27-9. https://meshb.nlm.nih.gov/record/ui?ui=D013973
2. Schally AV et al. Isolation and properties of porcine thyrotropin-releasing hormone. J Biol Chem (1969). https://pubmed.ncbi.nlm.nih.gov/4979236/
3. Study comparing the natural releasing hormone and synthetic pyroglutamyl-histidyl-proline amide. https://pubmed.ncbi.nlm.nih.gov/4982117/

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