Application and Pharmacology of Brigatinib
Oct 14,2019
Brigatinib (marketed as Alunbrig) is a small-molecule targeted cancer therapy being developed by ARIAD Pharmaceuticals, Inc.Brigatinib acts as both a anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) inhibitor.
Application
Brigatinib is an orally available inhibitor of receptor tyrosine kinases anaplastic lymphoma kinase (ALK) and the epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Brigatinib binds to and inhibits ALK kinase and ALK fusion proteins as well as EGFR and mutant forms. This leads to the inhibition of ALK kinase and EGFR kinase, disrupts their signaling pathways and eventually inhibits tumor cell growth in susceptible tumor cells. In addition, AP26113 appears to overcome mutation-based resistance. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development; ALK dysregulation and gene rearrangements are associated with a series of tumors. EGFR is overexpressed in a variety of cancer cell types.
Pharmacology
Mechanism of Action
Tyrosine kinase inhibitor with in vitro activity at clinically achievable concentrations against multiple kinases, including ALK, ROS1, insulinlike growth factor-1 receptor (IGF-1R), and FLT-3, as well as EGFR deletion and point mutations.
Brigatinib inhibited autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2, and S6 in in vitro and in vivo assays.
Exhibited in vivo antitumor activity against 4 mutant forms of EML4-ALK, including G1202R and L1196M mutants identified in NSCLC tumors in patients who have progressed on crizotinib.
Also reduced tumor burden and prolonged survival in mice implanted intracranially with an ALK-driven tumor cell line.
Absorption
Peak plasma time: 1-4 hr
Peak plasma concentration: 552 ng/mL (90 mg); 1452 ng/mL (180 mg)
AUC: 8165 ng·h/mL (90 mg); 20,276 ng·h/mL (180 mg)
Distribution
Protein bound: 66%
Vd: 153 L (steady-state)
Metabolism
Primarily metabolized by CYP2C8 and CYP3A4
Active metabolite: AP26123 is ~3-fold less potent than brigatinib
Elimination
Half-life: 25 hr
Oral clearance: 12.7 L/hr
Excretion: 65% feces; 25% urine (unchanged brigatinib represented 41% and 86% of the total radioactivity in feces and urine, respectively)
- Related articles
- Related Qustion
- Brigatinib: Indications, Dosing, Mechanism of Action and Side Effects Dec 16, 2024
Brigatinib is a new generation anaplastic lymphoma kinase (ALK) inhibitor.
- Brigatinib: Development History and Preclinical Studies Nov 19, 2024
Brigatinib, a crucial treatment for NSCLC patients with EGFR and ALK mutations, effectively inhibits ALK with unique features, overcoming resistance and offering hope in lung cancer treatment.
- The warnings and precautions of Brigatinib Mar 6, 2024
ALUNBRIG (Brigatinib) is a kinase inhibitor indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.
Resorcinol is a very white crystalline solid that becomes pink on exposure to light if not completely pure. Burns although ignition is difficult.It has a role as an erythropoietin inhibitor and a sensitiser.It is often used to make plastics....
Oct 14,2019APIcat_scratchingFluralaner (brand name Bravecto?) is used to treat and control flea and tick infestations in dogs and cats. After being ingested by a pet, fluralaner is distributed throughout the pet’s body.....
Oct 14,2019Chemical pesticides ?Brigatinib
1197953-54-0You may like
- Brigatinib.
- $0.00 / 1g
- 2025-01-10
- CAS:1197953-54-0
- Min. Order: 1g
- Purity: More Than 99%
- Supply Ability: 100kg/Month
- Brigatinib
- $0.00 / 1g
- 2025-01-09
- CAS:1197953-54-0
- Min. Order: 1g
- Purity: More Than 99%
- Supply Ability: 100kg/Month
- Brigatinib
- $0.00 / 1kg
- 2025-01-08
- CAS:1197953-54-0
- Min. Order: 1kg
- Purity: 99.0%
- Supply Ability: 10000