AMG 319
Clinical data
ATC code
  • None
Legal status
Legal status
  • Investigational
Identifiers
  • (S)-N-(1-[7-Fluoro-2-(pyridin-2-yl)quinolin-3-yl]ethyl)-9H-purin-6-amine
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC21H16FN7
Molar mass385.396 g·mol−1
3D model (JSmol)
  • C[C@@H](c1cc2ccc(cc2nc1c3ccccn3)F)Nc4c5c([nH]cn5)ncn4
  • InChI=1S/C21H16FN7/c1-12(28-21-19-20(25-10-24-19)26-11-27-21)15-8-13-5-6-14(22)9-17(13)29-18(15)16-4-2-3-7-23-16/h2-12H,1H3,(H2,24,25,26,27,28)/t12-/m0/s1
  • Key:KWRYMZHCQIOOEB-LBPRGKRZSA-N

AMG 319 is a drug developed by Amgen which acts as an inhibitor of the phosphoinositide 3-kinase enzyme subtype PI3Kδ. It was originally developed as an anti-inflammatory drug with potential applications in the treatment of autoimmune conditions such as rheumatoid arthritis, but subsequent research showed that it inhibits cell proliferation and might potentially have useful anti-cancer effects, and it has been put into clinical trials to assess its safety and tolerability in this application.[1][2]

Mechanism(s) of action

It is a potential immunotherapy because blocking PI3Kδ (PI3K p110δ) eliminates a group of inhibitory immune cells and may allow the immune system to better attack the cancer cells.[3] p110δ inactivation in regulatory T  cells unleashes CD8+ cytotoxic T  cells.[4]

Clinical trials

Its first clinical trial was a phase I/II study in adults with relapsed or refractory lymphoid malignancies.[5] This was due to run from 2011 to 2013.

In 2015/16 it started a phase II clinical trial as a neoadjuvant therapy for human papillomavirus (HPV) negative head and neck squamous-cell carcinoma (HNSCC) (prior to resection surgery).[3]

See also

References

  1. ↑ Cushing TD, Hao X, Shin Y, Andrews K, Brown M, Cardozo M, et al. (January 2015). "Discovery and in vivo evaluation of (S)-N-(1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine (AMG319) and related PI3Kδ inhibitors for inflammation and autoimmune disease". Journal of Medicinal Chemistry. 58 (1): 480–511. doi:10.1021/jm501624r. PMID 25469863.
  2. ↑ Lanasa MC, Glenn MJ, Mato AR, Allgood SD, Wong S, Amore B, et al. (December 2013). First-In-Human Study Of AMG 319, a Highly Selective, Small Molecule Inhibitor Of PI3Kδ, In Adult Patients With Relapsed Or Refractory Lymphoid Malignancies. 55th ASH Annual Meeting and Exposition.
  3. 1 2 Clinical trial number NCT02540928 for "AMG 319 in Human PapillomaVirus (HPV) Negative HNSCC" at ClinicalTrials.gov
  4. ↑ Ali K, Soond DR, Pineiro R, Hagemann T, Pearce W, Lim EL, et al. (June 2014). "Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer". Nature. 510 (7505): 407–411. Bibcode:2014Natur.510..407A. doi:10.1038/nature13444. PMC 4501086. PMID 24919154.
  5. ↑ Clinical trial number NCT01300026 for "A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 319 in Adult Subjects With Relapsed or Refractory Lymphoid Malignancies" at ClinicalTrials.gov
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