AMG 319

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]

AMG 319
Clinical data
ATC code
  • None
Legal status
Legal status
  • Investigational
Identifiers
IUPAC name
  • (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)
SMILES
  • C[C@@H](c1cc2ccc(cc2nc1c3ccccn3)F)Nc4c5c([nH]cn5)ncn4
InChI
  • 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

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. 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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