Tetracosactide Acetate Injection

Tetracosactide acetate injection, also known as 24 peptide corticotropin, is an artificially synthesized fragment 1-24 of adrenocorticotropic hormone (ACTH) that retains all the biological activity of natural ACTH, with lower antigenicity and longer lasting effects. Clinically, it is divided into short acting injection (for standard diagnosis) and long-acting sustained-release suspension injection (for treatment).Its core use is for the diagnosis of adrenal cortex function and the treatment of glucocorticoid sensitive inflammation/autoimmune diseases.

Ticotropin binds with high affinity to the melanocortin 2 receptor (MC2R) on the surface of adrenal cortical zona fascicula/reticular cells, activating the adenylate cyclase → cAMP → PKA signaling pathway, promoting the conversion of cholesterol to pregnenolone, and selectively stimulating the secretion of cortisol (glucocorticoid), low levels of androgen, and aldosterone. Compared to natural ACTH (39 peptide):Higher receptor selectivity: only activates MC2R, not MC1R/MC3R/MC4R, without side effects such as skin pigmentation and appetite disorders.More efficient effect: 1mg of ticagrel peptide ≈ 100U of natural ACTH, with a threefold increase in cortisol stimulation intensity, higher peak concentration, and longer duration.Extremely low antigenicity: Removing the 15 immunogenic amino acids at the C-terminus, the incidence of allergic reactions is less than 0.1% (natural ACTH is 5% -10%).

Inducing anti-inflammatory factors: Upregulating IL-10 and TGF - β, promoting regulatory T cell (Treg) differentiation, and enhancing immune tolerance.
Neuroprotective effects: Activate central MC4R, inhibit microglial activation, reduce excitatory amino acid release, resist neuronal apoptosis, used for neurological diseases.

Antioxidant stress: Enhance the activity of SOD and glutathione peroxidase in tissues, reduce the levels of MDA and ROS, and protect cells from oxidative damage.

This formulation features **100% bioavailability**. It bypasses hepatic first-pass metabolism entirely, sustaining steady blood drug levels and effectively eliminating the unstable gastrointestinal absorption commonly seen with oral hormone preparations. It also induces only mild inhibition on the hypothalamic-pituitary-adrenal (HPA) axis. The incidence of HPA axis suppression after long-term administration stays below 15%, a marked contrast to the 60%–80% rate associated with oral corticosteroids. Function can fully recover within 1 to 2 weeks after drug withdrawal, with no likelihood of severe adrenal atrophy.

Inhibits NF - κ B, AP-1, MAPK pathways through Gi/o protein, and directly blocks gene transcription and protein synthesis of pro-inflammatory factors such as TNF - α, IL-1 β, IL-6, IFN - γ, IL-17.n vitro experiments have confirmed that tacrolimus (10nM) can reduce TNF - α secretion by 72% and IL-6 by 68% in macrophages activated by lipopolysaccharide (LPS). This effect is not blocked by the GC receptor antagonist mifepristone and is confirmed to be non GC dependent.Compared with GC, its inhibition of pro-inflammatory factors is more selective - it does not affect the expression of anti-inflammatory factors IL-10 and TGF - β, avoiding "comprehensive immune suppression".

It exerts protective effects on vascular endothelial cells and delivers potent anti-inflammatory activity within blood vessels, helping to maintain the normal structure and function of the vascular system.Activate MC1R in endothelial cells, inhibit the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1).And E-selectin, block the adhesion and transmembrane migration of white blood cells (neutrophils, monocytes) to endothelial cells, and reduce inflammatory tissue infiltration.In vitro experiments showed that tacrolimus can reduce TNF - α - induced leukocyte adhesion rate in endothelial cells by 65%.

DNA methylation regulation: Mild activation of DNMT1 induces high methylation of inflammasome related gene promoters, achieving long-term anti-inflammatory memory - the anti-inflammatory effect can be maintained for 1-2 weeks after a single administration, significantly longer than exogenous GC.Inhibition of mitochondrial DNA (mtDNA) release: reduces mitochondrial damage and mtDNA leakage, blocks mtDNA activation of NLRP3 inflammasome, and suppresses "mitochondrial inflammation" from the source.

Mitochondrial function protection: Inhibits the opening of mitochondrial permeability transition pores (mPTP), stabilizes mitochondrial membrane potential, reduces the release of cytochrome C and apoptosis factors, protects cells from oxidative apoptosis, and reduces mitochondrial inflammatory signals.Inhibition of myeloperoxidase (MPO) activity: significantly reduces neutrophil MPO activity (30% lower than methylprednisolone), reduces the production of toxic oxidative products such as hypochlorous acid and chloramine, and alleviates tissue oxidative damage and inflammation aggravation.

Precise regulation of anti fibrosis: inhibits excessive activation of TGF - β/Smad3, reduces expression of α - SMA and fibronectin, and avoids excessive fibrosis; Simultaneously promoting the expression of matrix metalloproteinases (MMP1/3/9) and accelerating abnormal matrix degradation.
Stem cell mobilization: Stimulate the migration of bone marrow mesenchymal stem cells (MSCs) to the site of inflammation, differentiate into functional cells (such as endothelial cells, neurons, liver cells), and accelerate tissue repair.