Name: Donaxine iodomethylate
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

Gramine methiodide; (3-Indolylmethyl)trimethylammonium iodide; Ammonium, (indol-3-ylmethyl)trimethyl-, iodide

IUPAC Name

1H-indol-3-ylmethyl(trimethyl)azanium;iodide

Canonical SMILES

C[N+](C)(C)CC1=CNC2=CC=CC=C21.[I-]

InChI

InChI=1S/C12H17N2.HI/c1-14(2,3)9-10-8-13-12-7-5-4-6-11(10)12;/h4-8,13H,9H2,1-3H3;1H/q+1;/p-1

InChIKey

STGYYGWMNTXYAJ-UHFFFAOYSA-M

Melting Point

176-177 °C

Appearance

Light yellow powder

Shipping

-20°C (International: -20°C)

Storage

in a dry, cool and dark place

Donaxine iodomethylate is a synthetic cytotoxic compound and a potent ADC payload used in antibody-drug conjugates for targeted cancer therapy. Its mechanism of action involves alkylation of nucleophilic sites on DNA, leading to DNA crosslinking, inhibition of replication, and induction of apoptosis in proliferating tumor cells. The iodomethylate functional group facilitates covalent attachment to monoclonal antibodies through cleavable or non-cleavable linkers, allowing precise delivery of the cytotoxic payload in ADC applications.

Within antibody-drug conjugates, Donaxine iodomethylate is conjugated to antibodies via linker chemistries designed to maintain stability during systemic circulation while enabling controlled intracellular release. The ADC remains inactive in plasma, minimizing off-target toxicity. Upon receptor-mediated internalization into antigen-expressing tumor cells, enzymatic or chemical cleavage of the linker releases Donaxine iodomethylate, which interacts with nuclear DNA, causing replication arrest and apoptosis. This targeted mechanism ensures cytotoxic activity is restricted to tumor cells, supporting precise tumor-targeted therapy.

Applications of Donaxine iodomethylate include integration into ADCs targeting both hematologic malignancies and solid tumors with defined antigen expression. Its chemical structure is compatible with diverse linker strategies, enabling optimization of conjugation efficiency, intracellular release kinetics, and pharmacokinetic properties. Preclinical evaluations demonstrate reproducible cytotoxicity in target-expressing cells. Donaxine iodomethylate supports the development of ADCs with controlled DNA-damaging activity, providing mechanistically precise antitumor effects in tumor-targeted therapy constructs.

1. Methenamine's journey of 160 years: Repurposal of an old urinary antiseptic for treatment and hypoxic radiosensitization of cancers and glioblastoma

İlhan Elmaci, Meric A Altinoz, Alp Ozpinar, Aysel Ozpinar, Jennifer L Perez Clin Exp Pharmacol Physiol . 2019 May;46(5):407-412. doi: 10.1111/1440-1681.13070.

Methenamine (hexamethylenetetramine, hexamine, urotropine) is a compound discovered in 1859, which is still currently being used as a urinary antiseptic. Methenamine is highly soluble in water and polar solvents, and its molecular constitution is similar to adamantane compounds with tetrahedral cage like structure. In acidic conditions, methenamine decomposes to formaldehyde and ammonia. Recently, methenamine has gained a renewal of interest due to antibiotic-resistant bacteria urinary tract infections; interestingly, bacteria cannot gain resistance to formaldehyde. In 1968, David and Burkitt reported remarkable regression of four Burkitt Lymphoma patients in eight subjects who were treated with septicemine (a solution containing 6.3 g of methenamine iodomethylate and 1 g of methenamine sodium benzoate in 100 cc distilled water). Unfortunately, these striking observations did not gain interest in the medical community; despite experimental models that showed that methenamine synergized with hyperthermia, radiation, and chemotherapy to block cancer growth. As the hypoxic core of tumours have an acidic pH, it would be plausible to expect that methenamine would selectively target dormant, non-proliferative, and treatment-resistant cancer clones in large tumours. Moreover, previous data suggests that methenamine can be safely used intravenously and for treatment of infections of the central nervous system. It may therefore be an effective adjuvant in treatment of systemic cancers and glioblastoma.

2. [Specificity of action of piperidylcholine derivatives as substrates of cholinesterases of various origin]

N E Basova, E V Rozengart, A A Suvorov Zh Evol Biokhim Fiziol . 2009 Jan-Feb;45(1):25-33.

The review deals with study of enzymologic properties of a novel highly specific acetylcholinesterase substrate iodomethylate N-beta-(acetoxyethyl)piperidinium ("piperidylcholine") and its 30 derivatives that were tested as effectors of cholinesterases of mammals and various species of Pacific squids. It was proven for the first time that responsible for specificity of action was structure of cyclic ammonium grouping of the alcohol part of molecule of the ester substrate. Analysis of specificity is performed based on enzymatic analysis parameters - activity of catalytic center of cholinesterases and bimolecular constant of the reaction rate that are determined at optimal and low substrate concentrations. Among the specially synthesized group of thioester compounds there is revealed one more highly specific acetylcholine esterase substrate - N-beta-(acetoxyethyl)piperidinium.

What is Donaxine iodomethylate?

Donaxine iodomethylate is a potent cytotoxic compound used in the development of antibody-drug conjugates (ADCs). It functions as a small-molecule payload designed to selectively target tumor cells when linked to monoclonal antibodies, enhancing therapeutic efficacy while minimizing off-target effects.

11/12/2019

Could you kindly advise how Donaxine iodomethylate works in ADCs?

Donaxine iodomethylate exerts its cytotoxic effect by interfering with cellular processes such as DNA replication or microtubule function, depending on its specific chemical mechanism. When conjugated to an antibody, it allows selective delivery to antigen-expressing cells.

7/9/2021

We are interested in what types of linkers are compatible with Donaxine iodomethylate.

Donaxine iodomethylate can be conjugated using both cleavable and non-cleavable linkers. Selection depends on the intended release mechanism and therapeutic design. Cleavable linkers often respond to intracellular conditions such as pH or enzymatic activity.

16/3/2019

Good afternoon! Could you please advise what considerations are important for handling Donaxine iodomethylate?

Handling of Donaxine iodomethylate requires standard laboratory safety precautions for cytotoxic compounds, including personal protective equipment and containment strategies, to minimize exposure and ensure safety during conjugation and analytical procedures.

16/11/2016

Dear team, can Donaxine iodomethylate be used in preclinical ADC research?

Yes, Donaxine iodomethylate is commonly employed in preclinical ADC development to evaluate payload potency, linker stability, and target specificity. It serves as a reference cytotoxin for in vitro and in vivo efficacy studies.

29/8/2018

— Dr. Richard Evans, Senior Scientist (USA)

Donaxine iodomethylate arrived with high purity, which was essential for our experimental reproducibility.

16/3/2019

— Dr. Matthew Clarke, Oncology Scientist (USA)

Donaxine iodomethylate arrived quickly with full traceability, which is crucial for our ADC development projects.

29/8/2018

— Ms. Julia Weber, Senior Chemist (Germany)

High-quality Donaxine iodomethylate allowed us to conduct conjugation experiments with minimal variability.

16/11/2016

— Dr. Henry Foster, Project Lead (UK)

BOC Sciences provided excellent documentation for Donaxine iodomethylate, ensuring regulatory compliance in our research.