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	1608125-21-8 Y
PubChem CID	68947304
ChemSpider	35000181
UNII	19DG7G1U5Q
CompTox Dashboard (EPA)	DTXSID501046373
Chemical and physical data
Formula	C21H16FN7
Molar mass	385.406 g·mol−1
3D model (JSmol)	Interactive image
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]

Clinical trials

Its first clinical trial was a phase I/II study in adults with relapsed or refractory lymphoid malignancies.^[4] This was due to run from 2011 to 2013.^{[citation needed]}

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

• Duvelisib
• Idelalisib

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. 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