Erdafitinib | JNJ-42756493 | CAS#1346242-81-6 | FGFR inhibitor

MedKoo Cat#: 206440 | Name: Erdafitinib

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

Chemical Structure

Erdafitinib

CAS#1346242-81-6

Theoretical Analysis

MedKoo Cat#: 206440

Name: Erdafitinib

CAS#: 1346242-81-6

Chemical Formula: C25H30N6O2

Exact Mass: 446.2430

Molecular Weight: 446.55

Elemental Analysis: C, 67.24; H, 6.77; N, 18.82; O, 7.17

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 220.00	Ready to ship
50mg	USD 350.00	Ready to ship
100mg	USD 600.00	Ready to ship
250mg	USD 1,050.00	Ready to ship

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Synonym

JNJ-42756493; JNJ 42756493; JNJ42756493; Erdafitinib

IUPAC/Chemical Name

N1-(3,5-dimethoxyphenyl)-N2-isopropyl-N1-(3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl)ethane-1,2-diamine

InChi Key

OLAHOMJCDNXHFI-UHFFFAOYSA-N

InChi Code

InChI=1S/C25H30N6O2/c1-17(2)26-8-9-31(20-10-21(32-4)13-22(11-20)33-5)19-6-7-23-24(12-19)29-25(15-27-23)18-14-28-30(3)16-18/h6-7,10-17,26H,8-9H2,1-5H3

SMILES Code

CC(NCCN(C1=CC(OC)=CC(OC)=C1)C2=CC=C3N=CC(C4=CN(C)N=C4)=NC3=C2)C

Appearance

Yellow solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C9R08B23

QC Data

View QC data: current batch, Lot#C9R08B23

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Erdafitinib inhibits FGFR1/2/3/4 with IC50s of 1.2, 2.5, 3.0 and 5.7 nM, respectively.

In vitro activity:

The effects of a pan-FGFR tyrosine kinase inhibitor (JNJ-42756493) were evaluated. All four FGFRs were detected by qPCR in all CRC cell lines in vitro (Fig. 1a). Highest expression, as compared to the household gene HPRT, was for the FGFR2 gene in NCI-H716 (48 fold) and Caco2 cells (4 fold) (p < 0.05) (Fig. 1a). In agreement with these findings, FGFR inhibition significantly decreased cell growth and survival of NCI-H716 cells at concentrations of ≧ 0.5nM (p < 0.05), whereas ≧ 5000nM was required for all other cell lines, including Caco2 (Fig. 1b, Figure e1A). In NCI-H716 cells FGFR2 mRNA expression increased in a dose-dependent manner after drug treatment (Additional file 2: Figure e2A) while protein expression, which was detectable only in this cell line, decreased (Fig. 1c). Reference: BMC Cancer. 2015 Dec 16;15:946. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682227/

In vivo activity:

To assess the growth inhibiting effect of the drug, the relative tumour volumes of xenografted mice in the control group were compared to the group receiving only the FGFR inhibitor JNJ-42756493 (Tables 1 and and 2). Relative tumor volume of NCI-H716 tumors was delayed by drug treatment by 5 days (p < 0.05), with an increase in volume of on average 24.1 % of pretreatment values at 1 week (−15.9–92.73 %) while the control group increased by 88.2 % (−30.3–257.2 %) (p < 0.05) (Fig. 4). However when drug treatment was stopped, the relative tumor volume significantly increased between day 25 and 30 compared to vehicle treatment. The average increase in tumor volume one week after the end of drug treatment was 129.4 % (63.9–208.4 %) for the experimental group and 31.1 % (−25.2–89.1 %) for the control group (p < 0.05). Reference: BMC Cancer. 2015 Dec 16;15:946. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682227/

	Solvent	mg/mL	mM
Solubility
	DMSO	66.0	147.80
	Ethanol	45.0	100.77
	DMF	20.0	44.79
	DMF:PBS (pH 7.2) (1:7)	0.1	0.27

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 446.55 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Jin YY, Tong SQ, Tong M. Erdafitinib exerts the anticancer effect on urothelial carcinoma via induction of authophagy. Pharmazie. 2020 May 1;75(5):195-197. doi: 10.1691/ph.2020.9911. PMID: 32393427. 2. Verstraete M, Debucquoy A, Gonnissen A, Dok R, Isebaert S, Devos E, McBride W, Haustermans K. In vitro and in vivo evaluation of the radiosensitizing effect of a selective FGFR inhibitor (JNJ-42756493) for rectal cancer. BMC Cancer. 2015 Dec 16;15:946. doi: 10.1186/s12885-015-2000-8. PMID: 26675289; PMCID: PMC4682227.

In vitro protocol:

In vivo protocol:

1. Verstraete M, Debucquoy A, Gonnissen A, Dok R, Isebaert S, Devos E, McBride W, Haustermans K. In vitro and in vivo evaluation of the radiosensitizing effect of a selective FGFR inhibitor (JNJ-42756493) for rectal cancer. BMC Cancer. 2015 Dec 16;15:946. doi: 10.1186/s12885-015-2000-8. PMID: 26675289; PMCID: PMC4682227.

1: Montazeri K, Bellmunt J. Erdafitinib for the treatment of metastatic bladder cancer. Expert Rev Clin Pharmacol. 2019 Dec 6. doi: 10.1080/17512433.2020.1702025. [Epub ahead of print] PubMed PMID: 31810398. 2: de Almeida Carvalho LM, de Oliveira Sapori Avelar S, Haslam A, Gill J, Prasad V. Estimation of Percentage of Patients With Fibroblast Growth Factor Receptor Alterations Eligible for Off-label Use of Erdafitinib. JAMA Netw Open. 2019 Nov 1;2(11):e1916091. doi: 10.1001/jamanetworkopen.2019.16091. PubMed PMID: 31755953. 3: Dosne AG, Valade E, Stuyckens K, Li LY, Ouellet D, Perez-Ruixo JJ. Population Pharmacokinetics of Total and Free Erdafitinib in Adult Healthy Volunteers and Cancer Patients: Analysis of Phase 1 and Phase 2 Studies. J Clin Pharmacol. 2019 Nov 19. doi: 10.1002/jcph.1547. [Epub ahead of print] PubMed PMID: 31742712. 4: Chang SS. Re: Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. J Urol. 2019 Nov 11:10109701JU0000614704308269b. doi: 10.1097/01.JU.0000614704.30826.9b. [Epub ahead of print] PubMed PMID: 31710554. 5: Poggesi I, Li LY, Jiao J, Hellemans P, Rasschaert F, de Zwart L, Snoeys J, De Meulder M, Mamidi RNVS, Ouellet D. Effect of Fluconazole and Itraconazole on the Pharmacokinetics of Erdafitinib in Healthy Adults: A Randomized, Open-Label, Drug-Drug Interaction Study. Eur J Drug Metab Pharmacokinet. 2019 Oct 31. doi: 10.1007/s13318-019-00581-9. [Epub ahead of print] PubMed PMID: 31673875. 6: Loriot Y, Necchi A, Siefker-Radtke AO. Erdafitinib in Urothelial Carcinoma. Reply. N Engl J Med. 2019 Oct 17;381(16):1594-1595. doi: 10.1056/NEJMc1911187. PubMed PMID: 31618553. 7: Sonpavde G, Sjödahl G. Erdafitinib in Urothelial Carcinoma. N Engl J Med. 2019 Oct 17;381(16):1594. doi: 10.1056/NEJMc1911187. PubMed PMID: 31618552. 8: Sharma V, Vanidassane I. Erdafitinib in Urothelial Carcinoma. N Engl J Med. 2019 Oct 17;381(16):1593-1594. doi: 10.1056/NEJMc1911187. PubMed PMID: 31618551. 9: Li LY, Guo Y, Gonzalez M, Ouellet D. Effect of Plasma Protein Binding on the Pharmacokinetics of Erdafitinib: Results of an Integrated Cross-Study Analysis. J Clin Pharmacol. 2019 Oct 10. doi: 10.1002/jcph.1529. [Epub ahead of print] PubMed PMID: 31602692. 10: Marandino L, Raggi D, Giannatempo P, Farè E, Necchi A. Erdafitinib for the treatment of urothelial cancer. Expert Rev Anticancer Ther. 2019 Oct;19(10):835-846. doi: 10.1080/14737140.2019.1671190. Epub 2019 Oct 4. PubMed PMID: 31544541. 11: Hanna KS. Erdafitinib to treat urothelial carcinoma. Drugs Today (Barc). 2019 Aug;55(8):495-501. doi: 10.1358/dot.2019.55.8.3010573. Review. PubMed PMID: 31461086. 12: Burki TK. Erdafitinib for advanced urothelial carcinoma. Lancet Oncol. 2019 Sep;20(9):e469. doi: 10.1016/S1470-2045(19)30522-4. Epub 2019 Aug 1. PubMed PMID: 31378458. 13: Loriot Y, Necchi A, Park SH, Garcia-Donas J, Huddart R, Burgess E, Fleming M, Rezazadeh A, Mellado B, Varlamov S, Joshi M, Duran I, Tagawa ST, Zakharia Y, Zhong B, Stuyckens K, Santiago-Walker A, De Porre P, O'Hagan A, Avadhani A, Siefker-Radtke AO; BLC2001 Study Group. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2019 Jul 25;381(4):338-348. doi: 10.1056/NEJMoa1817323. PubMed PMID: 31340094. 14: Valade E, Dosne AG, Xie H, Kleiman R, Li LY, Perez-Ruixo JJ, Ouellet D. Assessment of the effect of erdafitinib on cardiac safety: analysis of ECGs and exposure-QTc in patients with advanced or refractory solid tumors. Cancer Chemother Pharmacol. 2019 Sep;84(3):621-633. doi: 10.1007/s00280-019-03896-1. Epub 2019 Jul 6. PubMed PMID: 31280362. 15: Markham A. Erdafitinib: First Global Approval. Drugs. 2019 Jun;79(9):1017-1021. doi: 10.1007/s40265-019-01142-9. PubMed PMID: 31161538. 16: Bahleda R, Italiano A, Hierro C, Mita A, Cervantes A, Chan N, Awad M, Calvo E, Moreno V, Govindan R, Spira A, Gonzalez M, Zhong B, Santiago-Walker A, Poggesi I, Parekh T, Xie H, Infante J, Tabernero J. Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors. Clin Cancer Res. 2019 Aug 15;25(16):4888-4897. doi: 10.1158/1078-0432.CCR-18-3334. Epub 2019 May 14. PubMed PMID: 31088831. 17: Erdafitinib Efficacious in Bladder Cancer. Cancer Discov. 2018 Aug;8(8):OF6. doi: 10.1158/2159-8290.CD-NB2018-085. Epub 2018 Jun 27. PubMed PMID: 29950346. 18: Nishina T, Takahashi S, Iwasawa R, Noguchi H, Aoki M, Doi T. Safety, pharmacokinetic, and pharmacodynamics of erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, in patients with advanced or refractory solid tumors. Invest New Drugs. 2018 Jun;36(3):424-434. doi: 10.1007/s10637-017-0514-4. Epub 2017 Sep 30. PubMed PMID: 28965185. 19: Karkera JD, Cardona GM, Bell K, Gaffney D, Portale JC, Santiago-Walker A, Moy CH, King P, Sharp M, Bahleda R, Luo FR, Alvarez JD, Lorenzi MV, Platero SJ. Oncogenic Characterization and Pharmacologic Sensitivity of Activating Fibroblast Growth Factor Receptor (FGFR) Genetic Alterations to the Selective FGFR Inhibitor Erdafitinib. Mol Cancer Ther. 2017 Aug;16(8):1717-1726. doi: 10.1158/1535-7163.MCT-16-0518. Epub 2017 Apr 17. PubMed PMID: 28416604. 20: Perera TPS, Jovcheva E, Mevellec L, Vialard J, De Lange D, Verhulst T, Paulussen C, Van De Ven K, King P, Freyne E, Rees DC, Squires M, Saxty G, Page M, Murray CW, Gilissen R, Ward G, Thompson NT, Newell DR, Cheng N, Xie L, Yang J, Platero SJ, Karkera JD, Moy C, Angibaud P, Laquerre S, Lorenzi MV. Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor. Mol Cancer Ther. 2017 Jun;16(6):1010-1020. doi: 10.1158/1535-7163.MCT-16-0589. Epub 2017 Mar 24. PubMed PMID: 28341788.