Brigatinib

Brigatinib

Clinical data
Routes of administration	By mouth
ATC code	None
Legal status
Legal status	Experimental
Identifiers
IUPAC name 5-Chloro-2-N-{4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyphenyl}-4-N-[2-(dimethylphosphoryl)phenyl]pyrimidine-2,4-diamine
CAS Number	1197953-54-0
PubChem (CID)	68165256
IUPHAR/BPS	7741
ChemSpider	34982928
UNII	HYW8DB273J
KEGG	D10866
PDB ligand ID	6GY (PDBe, RCSB PDB)
Chemical and physical data
Formula	C29H39ClN7O2P
Molar mass	528.22
3D model (Jmol)	Interactive image
SMILES COc1cc(ccc1Nc1ncc(Cl)c(Nc2ccccc2P(C)(C)=O)n1)N1CCC(CC1)N1CCN(C)CC1
InChI InChI=1S/C29H39ClN7O2P/c1-35-15-17-37(18-16-35)21-11-13-36(14-12-21)22-9-10-24(26(19-22)39-2)33-29-31-20-23(30)28(34-29)32-25-7-5-6-8-27(25)40(3,4)38/h5-10,19-21H,11-18H2,1-4H3,(H2,31,32,33,34) Key:AILRADAXUVEEIR-UHFFFAOYSA-N

Brigatinib (INN, previously known as AP26113) is an investigational small-molecule targeted cancer therapy being developed by ARIAD Pharmaceuticals, Inc. Brigatinib has exhibited activity as a potent dual inhibitor of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR).

ARIAD has begun a Phase 1/2 clinical trial of brigatinib based on cancer patients' molecular diagnoses in September 2011.

ALK was first identified as a chromosomal rearrangement in anaplastic large cell lymphoma (ALCL). Genetic studies indicate that abnormal expression of ALK is a key driver of certain types of non-small cell lung cancer (NSCLC) and neuroblastomas, as well as ALCL. Since ALK is generally not expressed in normal adult tissues, it represents a highly promising molecular target for cancer therapy.

Epidermal growth factor receptor (EGFR) is another validated target in NSCLC. Additionally, the T790M “gatekeeper” mutation is linked in approximately 50 percent of patients who grow resistant to first-generation EGFR inhibitors. While second-generation EGFR inhibitors are in development, clinical efficacy has been limited due to toxicity thought to be associated with inhibiting the native (endogenous or unmutated) EGFR. A therapy designed to target EGFR, the T790M mutation but avoiding inhibition of native EGFR is another promising molecular target for cancer therapy.

In 2016, brigatinib was granted orphan drug status by the FDA for treatment of NSCLC.

In 2010, ARIAD announced results of preclinical studies on brigatinib showing potent inhibition of the target protein and of mutant forms that are resistant to the first-generation ALK inhibitor, which currently is in clinical trials in patients with cancer. ARIAD scientists presented these data at the annual meeting of the American Association for Cancer Research (AACR) in Washington, D.C. in April.