Erdafitinib



Erdafitinib (also known as JNJ-42756493) is an orally bioavailable, pan fibroblast growth factor receptor (FGFR) inhibitor with potential antineoplastic activity. Upon oral administration, Erdafitinib binds to and inhibits FGFR, which may result in the inhibition of FGFR-related signal transduction pathways and thus the inhibition of tumour cell proliferation and tumour cell death in FGFR-overexpressing tumour cells. FGFR, upregulated in many tumour cell types, is a receptor tyrosine kinase essential to tumour cell proliferation, differentiation and survival.

Astex Pharmaceuticals discovered this drug and licensed it to Janssen Pharmaceuticals for further development. Erdafitinib has been used in trials studying the basic science and treatment of Tumour or Lymphoma.


 Common Name: Erdafitinib
Synonyms:  JNJ-42756493; JNJ42756493; JNJ 42756493; G-024; JNJ-493
IUPAC Name: N'-(3,5-dimethoxyphenyl)-N'-[3-(1-methylpyrazol-4-yl)quinoxalin-6-yl]-N-propan-2-ylethane-1,2-diamine
Molecular Formula: C25H30N6O2
Molecular Weight: 446.56 g/mol
CAS Number: 1346242-81-6
SMILES: CC(C)NCCN(C1=CC2=NC(=CN=C2C=C1)C3=CN(N=C3)C)C4=CC(=CC(=C4)OC)OC
Mechanism of Action: FGFR Inhibitor
Indication: Metastatic Urothelial Cancer
Development Stage: Phase II and III
Company: Janssen Pharmaceuticals/Astex Therapeutics Ltd.

FGFRs are a subset of tyrosine kinases which are upregulated in some tumours and influence tumour cell differentiation, proliferation, angiogenesis, and cell survival [1]. Activating mutations, amplifications and over-expression of FGFs have been implicated in the pathogenesis of a variety of human tumours including breast, prostate, colon and bladder cancers. Inhibition of FGFRs is expected to restore control of proliferative processes driven by these abnormalities.

Erdafitinib is being evaluated for safety and efficacy in phase II clinical trials for cholangiocarcinoma (bile duct cancer), gastric cancer, multiple myeloma, non-small cell lung cancer, Non-Hodgkin’s lymphoma, esophageal cancer and solid tumours [2]. Currently, JNJ42756493 is being evaluated by Janssen in Phase II and Phase III clinical trials in patients with advanced urothelial cancer. In March 2018, Erdafitinib was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration for treatment of urothelial cancer, which should expedite its development and regulatory review [3, 4].

Urothelial carcinoma, also known as transitional cell carcinoma, is a type of cancer that occurs in urinary system. It is the most common type of bladder cancer and cancer of the ureter, urethra and urachus. It is the second most common type of kidney cancer. Transitional cell carcinomas arise from the transitional epithelium, a tissue lining the inner surface of these hollow organs [5].

References:
  1. National Cancer Institute. NCI Drug Dictionary. Available at: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/pan-fgfr-kinase-inhibitor-bgj398. 
  2. "Erdafitinib - Janssen Pharmaceutica - AdisInsight". adisinsight.springer.com.
  3. https://www.jnj.com/media-center/press-releases/janssen-announces-us-fda-breakthrough-therapy-designation-for-erdafitinib-in-the-treatment-of-metastatic-urothelial-cancer
  4. https://astx.com/research-development/partnered-products-and-programs/jnj42756493-erdafitinib-fgfr-inhibitor-oncology/
  5. https://en.wikipedia.org/wiki/Transitional_cell_carcinoma


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