Methyl L-histidinate dihydrochloride (L-histidine methyl ester dihydrochloride, H-His-OMe·2HCl, CAS: 7389-87-9) is a chiral α-amino acid derivative with the molecular formula C₇H₁₃Cl₂N₃O₂ and molecular weight of 242.10 g/mol. Its structure consists of the methyl ester-protected L-histidine backbone, featuring an imidazole side chain (C₃H₃N₂) highly susceptible to metal chelation and proton transfer reactions, stabilized as a crystalline dihydrochloride salt. This unique architecture provides both the chiral center critical for stereoselective synthesis and a versatile imidazole ring capable of participating in hydrogen bonding, coordination chemistry, and enzyme-catalyzed transformations. As the most widely used carboxylic-protected derivative of the essential amino acid histidine, H-His-OMe·2HCl plays an indispensable role across multiple high-value research and industrial sectors: it serves as a key reactant in peptide chain growth via standard SPPS/Fmoc solid-phase synthesis; it is an essential biochemical probe for investigating histidine decarboxylase activity and histamine pathways, including its inhibitory effect on histidine decarboxylase in Sprague-Dawley rat stomach with an activity value of 1.8 μM; it is a standard reference compound for analytical method development; and it is a critical component in cell culture media formulations supplementing essential nutrients for optimal cell proliferation and protein synthesis; as well as a starting material for the synthesis of histidine-rich peptide sequences that enhance drug stability and bioavailability. Its production typically involves direct esterification of L-histidine with methanol under acid catalysis, followed by crystallization of the dihydrochloride salt from ethanol. With the global pharmaceutical R&D pipeline focusing increasingly on peptide-based therapeutics and histamine-modulating drugs, the demand for high-purity methyl L-histidinate dihydrochloride continues to expand steadily. Based on its chemical characteristics and industrial chain position, this article systematically analyzes international market dynamics of this compound, focusing on core application scenarios, competitive landscape, regional differences, regulatory trends, and future outlook, providing strategic references for industry participants.
Core Application Fields and Demand
Market demand for methyl L-histidinate dihydrochloride is highly concentrated in four major areas: peptide synthesis & pharmaceutical intermediate development (≈45% of global consumption), biochemical & enzyme research (≈20%), cell culture & biotechnology (≈20%), and nutritional & sports supplement research (≈15%). Its chiral purity and imidazole functionality drive widespread adoption.
In peptide synthesis and pharmaceutical research, H-His-OMe·2HCl is valued as a carboxylic-protected building block for incorporating histidine residues into peptide chains via solid-phase synthesis. It can be used as a reactant to synthesize imidazopyridine derivatives through Pictet-Spengler reactions with various aldehydes as well as to produce metal-chelating ligands such as N-methacryloyl-(L)-histidine methyl ester by reacting with methacryloyl chloride. It is incorporated into drug formulation processes specifically for creating histidine-rich peptides that enhance drug stability and efficacy. The global peptide therapeutics market, growing at 6-8% annually, directly drives demand for amino acid derivatives.
In biochemical research, methyl L-histidinate dihydrochloride serves as a substrate in enzymatic assays, primarily for studying enzyme kinetics and mechanisms of histidine-modifying enzymes including histidine decarboxylase and histidine kinases. It plays a significant role in understanding histidine metabolism and its biological roles, including the investigation of enzymatic pathways involved in histidine metabolism and their implications for metabolic disorders and therapeutic interventions.
In cell culture and biotechnology, the compound is added to cell culture media to support the growth of various cell lines, providing essential nutrients for optimal cell proliferation and protein synthesis. It is also used in studies investigating the role of histidine in neurotransmitter synthesis, providing insights into neurological disorders.
In nutritional science, amino acid derivatives including methyl L-histidinate dihydrochloride have been commercially used as ergogenic supplements, influencing the secretion of anabolic hormones and the supply of fuel during exercise, and are recognized to be beneficial as dietary supplements for athletic performance and metabolic health.
Major Market Participants
The global supply system for methyl L-histidinate dihydrochloride follows a pattern of “specialized fine chemical and research reagent manufacturers, primarily in North America, Europe, China and India, serving both small-scale R&D and large-scale industrial production.” The compound is commonly supplied as a white crystalline powder with purity ranging from 97% to ≥99% as verified by HPLC, with typical specifications including melting point ~200°C and specific optical rotation [α]²⁰ᴰ = 10 ± 2° (c=2 in water).
Factors that distinguish market participants include the ability to offer validated chiral purity, cGMP-compliant documentation for pharmaceutical applications, and flexible packaging from bulk kilogram scale to smaller R&D quantities.
Shanghai XinChem Co., Ltd. (XinChem) has established a reliable supply chain for high-purity methyl L-histidinate dihydrochloride. Our product meets rigorous specifications—purity ≥97% to ≥99% (HPLC), white crystalline powder, controlled impurity profiles, and strict heavy metal limits—fully complying with global peptide synthesis and biochemical research standards.
Several international reagent manufacturers supply H-His-OMe·2HCl for research applications. However, XinChem provides a cost-effective, scalable alternative with custom packaging options for both research customers (gram quantities) and industrial customers (bulk kilograms).
Regional Market Dynamics
Global demand for methyl L-histidinate dihydrochloride shows regional differentiation: “North America and Europe lead in pharmaceutical R&D and peptide-based drug development, Asia-Pacific dominates contract research and manufacturing (CRO/CDMO), and Latin America & Middle East/Africa follow as emerging research hubs with growing biotech investments.”
North America (United States + Canada) accounts for approximately 35-40% of global demand, driven by a robust biopharmaceutical sector, extensive peptide drug discovery pipelines, and strong academic life science research funding. Regulatory documentation (COA, DMF support, residual solvents analysis) and compliance with FDA guidelines are strictly required for pharmaceutical applications.
Europe constitutes approximately 30-35% of global demand, with Germany, Switzerland, the United Kingdom, and France being major consumers. The region‘s strong peptide therapeutics industry, advanced neuroscience research, and strict adherence to REACH regulations push suppliers to maintain rigorous documentation standards. The emphasis on validation of chiral purity and product consistency for peptide synthesis intermediates is particularly pronounced.
Asia-Pacific is the fastest-growing market, increasing at a CAGR of 7-9%. China has emerged as a dominant manufacturing hub for fine chemical intermediates and peptide building blocks, with cost-competitive production and comprehensive supply chain integration. Major growth drivers include significant government investment in biotechnology and pharmaceutical innovation, the expansion of CRO/CDMO service providers, and increasing domestic demand for research reagents. Japan and South Korea also demand high-purity grades for their semiconductor-adjacent biochemical and advanced pharmaceutical applications.
Regulatory and Environmental Considerations
As a chiral amino acid derivative intended for biochemical research and pharmaceutical applications, methyl L-histidinate dihydrochloride (CAS 7389-87-9) must meet stringent quality standards. The compound is classified as: Xi (Irritant) with risk phrase R36/37/38 (irritating to eyes, respiratory system, and skin). Safety precautions: S22 (do not breathe dust), S24/25 (avoid contact with skin and eyes). The hazard classification is based on the potential for skin/respiratory irritation and serious eye irritation upon repeated or prolonged contact. It is not classified as carcinogenic or mutagenic, lacks acute toxicity reports at normal handling levels, and is not considered a marine pollutant. It is hygroscopic and requires storage under inert atmosphere at 2-8°C in tightly sealed containers, away from moisture, and should be stored in powder form at -20°C for up to 3 years or at 2-8°C for up to 2 years, and dissolved in solvent at -80°C for 1 year.
In the EU, the compound is subject to REACH regulations as a research chemical rather than a registered industrial intermediate in large volumes; however, importers and manufacturers must provide Safety Data Sheets (SDS). Suppliers must label the substance according to CLP standards with Xi hazard classification.
In the US, the EPA regulates the compound under TSCA as a research chemical. Import shipments are subject to regular compliance review. No specific FDA monograph exists for this intermediate, but its use in pharmaceutical API synthesis must adhere to cGMP guidelines and ICH Q7 quality standards.
In China, methyl L-histidinate dihydrochloride is listed in the Inventory of Existing Chemical Substances and must comply with GB standards. Safety production licenses are required for manufacturing facilities. The compound is assigned customs HS Code 29332900.
Environmentally, the compound is readily biodegradable with no anticipated bioaccumulation potential and negligible aquatic toxicity at expected environmental release levels.Manufacturing generates waste streams containing methanol and hydrochloric acid, requiring neutralization and responsible disposal. Green chemistry efforts focus on acid-catalyzed esterification with methanol recovery and solvent recycling from dihydrochloride crystallization.
Future Outlook
The market outlook for methyl L-histidinate dihydrochloride is tied to four core drivers: (1) the rapid expansion of the global peptide therapeutics market (estimated to reach USD 50-55 billion by 2030); (2) increasing research on histamine-modulating drugs for allergy, inflammation, and neurodegenerative disorders; (3) the growth of the contract research and biotech service sector (CRO/CDMO) in Asia-Pacific; and (4) rising investments in life sciences and biopharmaceutical innovation in emerging economies. The global market for amino acid derivatives is projected to grow at a CAGR of 5.5-6.5% over the next five years, with the pepticle synthesis segment, driven by growth in metabolic disease drugs, outperforming the broader market.
On the demand side, the peptide API manufacturing sector will be the largest and fastest-growing driver, fueled by the approval of new peptide-based drugs for diabetes (GLP-1 agonists) and oncology. Research into histamine H3 and H4 receptor modulators continues to expand, creating new demand for histidine derivatives. The expansion of academic research and government-funded life science initiatives in Asia-Pacific will drive steady demand growth for research-grade material at the gram-to-kilogram scale.
Challenges include: raw material cost dependence on L-histidine supply sourced from fermentation or protein hydrolysis； competition from new histidine derivatives offering alternative protection strategies (Fmoc-His-OMe, Boc-His-OMe) for different synthetic protocols; and the need for stringent storage conditions (inert atmosphere, low temperature) to prevent hydrolysis and racemization, which limits certain distribution channels and requires cold-chain logistics. Enterprises should focus on providing validated chiral purity and DMF-ready documentation, ensuring cold-chain integrity for distribution, and building long-term supply partnerships with peptide API manufacturers, CROs, and research institutions.
Shanghai XinChem Co., Ltd. (XinChem)
As a world-leading supplier of organic chemicals, chiral intermediates, and pharmaceutical building blocks, Shanghai XinChem Co., Ltd. (XinChem) has always focused on the innovative needs of the peptide synthesis, pharmaceutical research, and biotechnology industries. Relying on core technological advantages in chiral amino acid derivative manufacturing and quality control, we provide high-purity Methyl L-histidinate dihydrochloride (L-His-OMe·2HCl, CAS: 7389-87-9) to global customers. Our product is manufactured under strict quality management, achieving consistent purity ≥97-99% (HPLC), white crystalline powder appearance, low residual solvents, and low heavy metals, fully complying with pharmaceutical intermediate and biochemical research standards. It is an ideal chiral building block for peptide APIs, enzyme assays, and cell culture media.
1. Technical Advantages
- High Chiral Purity: Our product achieves purity ≥97-99% (HPLC) with specific optical rotation [α]²⁰ᴰ = 9-12° (c=2 in water), confirming the L-configuration and ensuring stereospecific performance in peptide synthesis.
- Low Impurity Profile & Stability: Product is supplied as a stable white crystalline powder (mp ~200-207°C dec.), dissolved in water and DMSO, controlled residual solvents (<0.5% total), heavy metals (≤10 ppm), and moisture (<0.5%).
- Batch Consistency: Batch-to-batch variation controlled within 0.5% for HPLC purity, ensuring consistent coupling efficiency in SPPS workflows.
2. Product Advantages
- Versatile Synthetic Utility: Widely used in solid-phase peptide synthesis (SPPS), Pictet-Spengler heterocycle synthesis, metal-chelate polymer synthesis, and neuropharmacological assay development.
- Excellent Solubility: Soluble in water, DMSO (27.5 mg/mL, 113.59 mM), and methanol; fully compatible with standard peptide synthesis solvents and cell culture media.
- Convenient Formulation: Supplied as a stable, non-hygroscopic (when properly sealed) crystalline powder for easy handling and long-term storage stability.
- Flexible Packaging: 5g, 10g, 25g, 50g, 100g glass bottles (R&D), 500g and 1kg HDPE containers (pilot), and 5kg, 10kg, 25kg fiber drums (industrial), as well as full custom packaging upon request.
- Reliable Supply Chain: Annual capacity 10-50 metric tons, with dedicated cold-chain warehousing (2-8°C, nitrogen blanket) and just-in-time delivery capabilities.
3. Application Fields
- Peptide Synthesis: Carboxylic-protected histidine building block for SPPS/Fmoc solid-phase peptide synthesis; synthesis of histidine-rich peptides and bioactive peptide sequences.
- Pharmaceutical Intermediates: Building block for peptide-based drug candidates (GLP-1 analogs, integrin inhibitors, antimicrobial peptides) and precursor for optically pure L-(+)-ergothioneine.
- Biochemical Research: Substrate for enzyme assays targeting histidine decarboxylase (activity value 1.8 μM in rat stomach models) and histidine-modifying enzymes, investigating histamine metabolic pathways, and essential tool for neuropharmacology and neurotransmitter-related research.
- Cell Culture & Biotechnology: Nutritional supplement in mammalian cell culture media formulations, additive for hybridoma and CHO cell lines, supplement for optimization of protein expression.
- Analytical Chemistry: Standard reference compound for HPLC and LC-MS method validation, calibration standard for quantitation of histidine derivatives in complex biological matrices.
4. Service Support
Our technical team provides impurity profiling (enantiomeric purity, residual solvents, heavy metals), custom packaging, and regulatory support (COA, TDS, MSDS, REACH, TSCA, DMF preparation for pharmaceutical customers). We offer just-in-time delivery and cold-chain logistics. Custom synthesis for analog derivatives available.
5. Why Choose XinChem
- Professionalism: 20+ years in the chiral intermediate, pharmaceutical, and biochemical research industry.
- Flexibility: Tailored to customer purity, enantiopurity, and packaging requirements.
- Cost‑effectiveness: High quality at competitive prices.
Contact us now to start cooperation!
Website: www.xinchem.com
Email: sales1@xinchem.com
WhatsApp: +86 18049800532
Post time: May-11-2026