Motolimod

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Motolimod
Motolimod structure.png
Identifiers
  • 2-amino-N,N-dipropyl-8-[4-(pyrrolidine-1-carbonyl)phenyl]-3H-1-benzazepine-4-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C28H34N4O2
Molar mass 458.606 g·mol−1
3D model (JSmol)
  • CCCN(CCC)C(=O)C1=CC2=C(C=C(C=C2)C3=CC=C(C=C3)C(=O)N4CCCC4)N=C(C1)N
  • InChI=1S/C28H34N4O2/c1-3-13-31(14-4-2)28(34)24-17-23-12-11-22(18-25(23)30-26(29)19-24)20-7-9-21(10-8-20)27(33)32-15-5-6-16-32/h7-12,17-18H,3-6,13-16,19H2,1-2H3,(H2,29,30)
  • Key:QSPOQCXMGPDIHI-UHFFFAOYSA-N

Motolimod (VTX-2337) is a drug which acts as a potent and selective agonist of toll-like receptor 8 (TLR8), a receptor involved in the regulation of the immune system. It is used to stimulate the immune system, and has potential application as an adjuvant therapy in cancer chemotherapy, although clinical trials have shown only modest benefits. [1] [2] It also worsens neuropathic pain in animal models and has been used to research the potential of targeting TLR8 in some kinds of chronic pain syndromes. [3] [4]

See also

Related Research Articles

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<span class="mw-page-title-main">Toll-like receptor</span> Pain receptors and inflammation

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<span class="mw-page-title-main">AHCC</span> Dietary supplement

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<span class="mw-page-title-main">Pertuzumab</span> Pharmaceutical drug

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<span class="mw-page-title-main">Toll-like receptor 4</span> Protein-coding gene in the species Homo sapiens

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Vesatolimod (GS-9620) is an antiviral drug developed by Gilead Sciences, which acts as a potent and selective agonist of Toll-like receptor 7 (TLR7), a receptor involved in the regulation of the immune system. It is used to stimulate the immune system, which can increase its ability to combat chronic viral infections. Vesatolimod is in clinical trials to determine whether it is safe and effective in patients with Hepatitis B and HIV/AIDS, and has also shown activity against other viral diseases such as norovirus and enterovirus 71.

<span class="mw-page-title-main">CU-CPT9a</span>

CU-CPT9a is a drug which acts as a potent and selective antagonist of Toll-like receptor 8 (TLR8), with an IC50 of 0.5nM. Activation of toll-like receptors triggers release of cytokines and other signalling factors, leading to inflammation. This is an essential part of the immune system's response to infection, but chronic activation of TLR signalling is thought to be involved in various inflammatory and autoimmune disorders. CU-CPT9a has immunosuppressant properties, and may have applications in the treatment of autoimmune disorders, as well as being used in scientific research into the function of TLR8.

References

  1. Monk BJ, Brady MF, Aghajanian C, Lankes HA, Rizack T, Leach J, et al. (May 2017). "A phase 2, randomized, double-blind, placebo-controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners study". Annals of Oncology. 28 (5): 996–1004. doi: 10.1093/annonc/mdx049 . PMC   5406764 . PMID   28453702.
  2. Ferris RL, Saba NF, Gitlitz BJ, Haddad R, Sukari A, Neupane P, et al. (November 2018). "Effect of Adding Motolimod to Standard Combination Chemotherapy and Cetuximab Treatment of Patients With Squamous Cell Carcinoma of the Head and Neck: The Active8 Randomized Clinical Trial". JAMA Oncology. 4 (11): 1583–1588. doi: 10.1001/jamaoncol.2018.1888 . PMC   6248084 . PMID   29931076.
  3. Zhang ZJ, Guo JS, Li SS, Wu XB, Cao DL, Jiang BC, et al. (December 2018). "TLR8 and its endogenous ligand miR-21 contribute to neuropathic pain in murine DRG". The Journal of Experimental Medicine. 215 (12): 3019–3037. doi: 10.1084/jem.20180800 . PMC   6279408 . PMID   30455267.
  4. Zhao LX, Jiang M, Bai XQ, Cao DL, Wu XB, Zhang J, et al. (December 2020). "TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice". Neuroscience Bulletin. doi: 10.1007/s12264-020-00621-4 . PMC   8055805 . PMID   33355900.