ATN-161- 5mg, 60mg

STRUCTURE

Sequence: Ac-Pro-His-Ser-Cys-Asn-NH2

Molecular Formula: C₂₃H₃₅N₉O₈S 

Molecular Weight: 597.64 g/mol

CAS: 262438-43-7 

Peptide Purity: greater than 98%

Other details: No TFA Salt

Storage: Lyophilized peptide must be stored at -20°C and peptide solution at +4°C

DESCRIPTION

ATN-161 is a pentapeptide derived from the sequence of the α5β1 integrin, which represents a critical binding site for fibronectin, an extracellular matrix (ECM) glycoprotein. This peptide inhibits interactions between cells and the extracellular matrix, a crucial process for tumor growth and metastasis.

ATN-161 has been modified with acetylation (Ac) at the N-terminus and amidation (NH2) at the C-terminus, which enhances its resistance to enzymatic degradation. These modifications prolong the peptide’s half-life in circulation, ensuring that it remains active long enough to exert its therapeutic effects.

In preclinical studies, ATN-161 has demonstrated:

• Good bioavailability
• Prolonged action
• Rapid clearance

Further development of formulations such as liposomal ATN-161 or PEGylation (conjugating the peptide with polyethylene glycol) could potentially improve its pharmacokinetic profile, increasing stability and allowing for more consistent delivery over time.

ATN-161 works by inhibiting integrins, particularly those involved in interactions with fibronectin. Integrins are proteins that mediate interactions between cells and the extracellular matrix, regulating crucial processes like cell survival, proliferation, migration, and adhesion. By inhibiting these interactions, ATN-161 has several effects on tumor cells and the tumor microenvironment:

• Inhibition of Angiogenesis: ATN-161 reduces the formation of new blood vessels necessary for tumor growth by blocking the interaction between integrins α5β1 and αvβ3 with fibronectin. Angiogenesis is a key process that allows tumors to obtain a continuous supply of nutrients and oxygen to grow.
• Inhibition of Cell Migration: ATN-161 prevents tumor cells from migrating through the extracellular matrix, reducing the tumor’s ability to metastasize to other organs. This is particularly important for the treatment of malignant tumors that tend to spread rapidly.
• Interference with Cell Survival Signaling: By blocking cell-matrix interactions, ATN-161 can disrupt signaling pathways that promote tumor cell survival. Inhibiting these pathways can increase apoptosis (programmed cell death) in tumor cells.

Beyond its role in blocking integrins and inhibiting angiogenesis and metastasis, ATN-161 also influences several downstream signaling pathways, offering a broader impact on cellular behavior:

1. Inhibition of Integrin-Mediated Signaling:

   • Integrin α5β1 and αvβ3 are involved in numerous pro-survival and migration pathways. By binding to the integrin receptors, ATN-161 interferes with the activation of focal adhesion kinase (FAK) and Src kinase, which are key regulators of cell movement, survival, and proliferation.
   • The inhibition of FAK/Src signaling leads to decreased cellular adhesion and disruption of cytoskeletal organization, which prevents cancer cells from efficiently migrating and invading other tissues.

2. Modulation of the Tumor Microenvironment:

   • ATN-161 does not just affect tumor cells directly; it also has an impact on the tumor microenvironment. By inhibiting integrin signaling, ATN-161 reduces stromal-tumor interactions, which are critical for supporting tumor growth. This includes reducing the recruitment of fibroblasts and immune cells that can aid in tumor growth and metastasis.

3. Suppression of Inflammatory Pathways:

   • The inhibition of integrin-mediated pathways also leads to a reduction in pro-inflammatory cytokine production, particularly in the NF-κB pathway. This effect could be beneficial not only in cancer therapy but also in the treatment of chronic inflammatory diseases, where integrins play a role in the recruitment of inflammatory cells to sites of tissue damage.

ATN-161 has been studied primarily in the context of cancer, but it may have applications in other diseases where integrins play a key role in disease progression. Below are some of the conditions that could benefit from the use of ATN-161:

1. Solid Tumors
   • Breast Cancer: Preclinical studies have shown that ATN-161 significantly reduces tumor growth and metastasis in breast cancer models. By blocking integrins, it prevents tumor cells from invading surrounding tissues and forming new metastatic colonies.
   • Glioblastoma: Glioblastoma is a highly malignant and difficult-to-treat brain tumor. ATN-161 has been shown to reduce glioblastoma cell invasiveness and inhibit angiogenesis, improving the response to treatments like radiotherapy.
   • Lung Cancer: Non-small cell lung cancer (NSCLC), in particular, may benefit from the use of ATN-161 in combination with standard therapies. In preclinical studies, the peptide has been shown to reduce tumor growth and limit metastasis formation.
2. Metastatic Tumors
   • ATN-161 could be particularly useful in treating tumors that tend to metastasize, such as colorectal cancer and melanoma. By inhibiting tumor cell migration, the peptide may reduce the spread of cancer to other organs and prolong patient survival.
3.  Hematologic Neoplasms
   • Although most research on ATN-161 has focused on solid tumors, there is potential for its use in hematologic malignancies, such as leukemia or multiple myeloma, where cell-extracellular matrix interactions play a role in disease progression.
4. Chronic Inflammatory Diseases
   • Integrins are also involved in the inflammatory response and the infiltration of leukocytes into damaged tissues. ATN-161 could be studied for the treatment of chronic inflammatory diseases, such as rheumatoid arthritis or inflammatory bowel disease, where modulating cell adhesion might have a therapeutic effect.
5.  Fibrosis
   • Integrins play a role in the pathogenesis of fibrosis, a pathological process that leads to the accumulation of scar tissue in organs such as the lungs (pulmonary fibrosis), liver (cirrhosis), and kidneys (chronic nephropathy). ATN-161 could inhibit the accumulation of fibroblasts and collagen deposition, slowing fibrosis progression.
6. Osteoporosis
   • Bone resorption and remodeling are regulated by integrin signaling in osteoclasts. By inhibiting these pathways, ATN-161 could potentially be explored as a treatment for osteoporosis, reducing bone loss and increasing bone density.
7. Cardiovascular Diseases
   • Integrins are involved in the remodeling of blood vessels during atherosclerosis and cardiovascular inflammation. Inhibitors like ATN-161 may help to prevent the buildup of plaque in arteries and reduce the risk of thrombosis.

ATN-161 presents several advantages:

• Low Toxicity Profile: Preclinical and clinical studies on ATN-161 have shown a relatively low toxicity profile.
• Specific Targeting: ATN-161 acts specifically on integrins involved in tumor growth and metastasis, reducing the risk of systemic side effects that could arise from inhibiting other cellular pathways.
• Broad Spectrum of Action: ATN-161 has demonstrated activity in various preclinical tumor models, including solid tumors such as breast cancer, glioblastoma, and lung cancer. This suggests that it could be used to treat multiple types of cancer.

Numerous preclinical studies have demonstrated the efficacy of ATN-161 in reducing tumor growth and metastasis in various animal models. A key study showed that the peptide significantly reduced liver metastasis formation in a mouse model of colorectal cancer. In another study, ATN-161 was found to enhance the effectiveness of chemotherapy in a model of metastatic breast cancer.

In phase I clinical trials, ATN-161 was well-tolerated, with few significant side effects. Some patients with advanced solid tumors showed disease stabilization, suggesting that the peptide could be useful as a maintenance therapy to prevent tumor progression.

REFERENCES

P. Khalili et al., "A non-RGD-based integrin binding peptide (ATN-161) blocks breast cancer growth and metastasis in vivo" [PubMed]

F. Donate et al., "Pharmacology of the novel antiangiogenic peptide ATN-161 (Ac-PHSCN-NH2): observation of a U-shaped dose-response curve in several preclinical models of angiogenesis and tumor growth" [PubMed]

B.J. Beddingfield et al., "The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2 Infection" [PubMed]

M.E. Cianfrocca et al., "Phase 1 trial of the antiangiogenic peptide ATN-161 (Ac-PHSCN-NH(2)), a beta integrin antagonist, in patients with solid tumours" [PubMed]

D.E. Edwards et al., "Integrin α5β1 inhibition by ATN-161 reduces neuroinflammation and is neuroprotective in ischemic stroke" [PubMed]

O. Stoeltzing et al., "Inhibition of integrin alpha5beta1 function with a small peptide (ATN-161) plus continuous 5-FU infusion reduces colorectal liver metastases and improves survival in mice" [PubMed]

DISCLAIMER

This product is intendend for lab research and development use only. These studies are performed outside of the body. This product is not medicines or drugs and has not been approved by the FDA or EMA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law. This product should only be handled by licensed, qualified professionals.

All product information provided on this website is for informational and educational purposes only.