Identification

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Name
Erdafitinib
Accession Number
DB12147
Type
Small Molecule
Groups
Approved, Investigational
Description

In early April of 2019, the US FDA approved Janssen Pharmaceutical Companies' brand name Balversa (erdafitinib) as the first-ever fibroblast growth factor receptor (FGFR) kinase inhibitor indicated for patients with locally advanced or metastatic urothelial carcinoma, with susceptible FGFR3 or FGFR2 genetic alterations, that has progressed during or following platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy 4,5. At the same time, the FDA also approved the therascreen FGFR RGQ RT-PCR Kit (Qiagen) for utilization as a companion diagnostic with erdafitinib for selecting patients for the indicated therapy 4,5.

Erdafitinib's innovation lies in the fact that it is the first personalized treatment targeting susceptible FGFR genetic alterations for patients with metastatic bladder cancer, which demonstrates the design of erdafitinib in developing more personalized and precision medicines with the capacity to target cancer treatment to a patient's specific genetic mutation 4,5. Considering urothelial cancer is statistically the fourth most common kind of cancer in the world 7, the introduction of erdafitinib offers a welcome new option in the ever-expanding therapeutic tool kit to treat such prevalent medical conditions.

Nevertheless, although erdafitinib was granted Breakthrough Therapy designation and Accelerated Approval from the FDA so as to allow the agency to focus on and expedite the approval process for a medication indicated for a serious condition that fills an unmet medical need using clinical trial data that is believed to predict a genuine clinical benefit for patients with the given condition, such designations mean further ongoing clinical trials are necessary to confirm the clinical benefit of erdafitinib going forward 4,5.

Structure
Thumb
Synonyms
  • Erdafitinib
External IDs
JNJ-42756493
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BalversaTablet, film coated5 mg/1OralJanssen Products LP2019-04-12Not applicableUs
BalversaTablet, film coated4 mg/1OralJanssen Products LP2019-04-12Not applicableUs
BalversaTablet, film coated3 mg/1OralJanssen Products LP2019-04-12Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
890E37NHMV
CAS number
1346242-81-6
Weight
Average: 446.555
Monoisotopic: 446.24302423
Chemical Formula
C25H30N6O2
InChI Key
OLAHOMJCDNXHFI-UHFFFAOYSA-N
InChI
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
IUPAC Name
N-(3,5-dimethoxyphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-N-{2-[(propan-2-yl)amino]ethyl}quinoxalin-6-amine
SMILES
COC1=CC(=CC(OC)=C1)N(CCNC(C)C)C1=CC=C2N=CC(=NC2=C1)C1=CN(C)N=C1

Pharmacology

Indication

Erdafitinib is a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor Label1,2,3 that is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma that has: i) susceptible FGFR3 or FGFR2 genetic alterations and has Label, ii) progressed during or following at least one line of prior platinum-containing chemotherapy including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy Label.

The selection of patients for the treatment of locally advanced or metastatic urothelial carcinoma with erdafitinib should be based on the presence of susceptible FGFR genetic alterations in tumor specimens as detected by an FDA-approved companion diagnostic like the FDA approved therascreen FGFR RGQ RT-PCR Kit as developed by QIAGEN Label.

This above indication is approved under accelerated approval by the US FDA based on tumor response rate Label. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials Label.

Associated Conditions
Pharmacodynamics

Upon administration, it was observed that erdafitinib increased serum phosphate level as a consequence of FGFR inhibition Label1,3. Erdafitinib should be increased to the maximum recommended dose to achieve target serum phosphate levels of 5.5– 7.0 mg/dL in early cycles with continuous daily dosing Label1,3.

Subsequently, in erfatinib clinical trials, the use of drugs which could increase serum phosphate levels, such as potassium phosphate supplements, vitamin D supplements, antacids, phosphate-containing enemas or laxatives, and medications known to have phosphate as an excipient were prohibited unless no alternatives existed Label1,3. To manage phosphate elevation, phosphate binders were utilized Label1,3. Additionally, the concomitant use of agents that can alter serum phosphate levels before the initial erfatinib dose increase period based on serum phosphate levels was also avoided Label1,3.

Furthermore, based on the evaluation of QTc interval in an open-label, dose escalation, and dose expansion study in 187 patients with cancer, erdafitinib had no large effect (i.e., > 20 ms) on the QTc interval Label.

Mechanism of action

Urothelial cancer is statistically the fourth most common kind of cancer in the world 7. In general, such urothelial cancers originate in the urothelium - or the transitional epithelium - a membrane that covers the renal pelvis to the ureter, the bladder, and the proximal two-thirds of the urethra 7. While 90 to 95% of urothelial cancers are bladder cancers and the other 5 to 10% are upper tract urothelial cancers, the bladder cancers can also be either superficial or invasive (either not having or having invaded the deeper layers of the bladder) 7.

Moreover, fibroblast growth factor receptor (FGFR) is a transmembrane protein that is expressed ubiquitously in normal tissues and is involved in various endogenous bio-physiological processes including the homeostasis of phosphate and vitamin D, cell proliferation, cell anti-apoptotic signaling, and cell migration in a variety of cell types 1. Concurrently, genetic mutations or changes like deregulation of FGFR pathways and FGFR aberrations such as gene amplification, point mutations, and chromosomal translocations have been implicated in the pathogenesis of urothelial cancer, including the possibility of such changes to all four FGFR genes (FGFR1, FGFR2, FGFR3, and FGFR4) 1,7. Changes to the FGFR genes are consequently thought to promote cell proliferation, migration, angiogenesis, and anti-apoptosis in many cancers including urothelial cancer 1,7.

Erdafitinib is subsequently an oral selective pan-FGFR kinase inhibitor that binds to and inhibits the enzymatic activity of expressed FGFR1, FGFR2, FGFR3, and FGFR4 based on in vitro data Label1,3. In particular, erdafitinib demonstrates inhibition of FGFR phosphorylation and signaling as well as decreased cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions Label1,3. Erdafitinib demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer Label1,3.

TargetActionsOrganism
AFibroblast growth factor receptor 1
inhibitor
Humans
AFibroblast growth factor receptor 2
inhibitor
Humans
AFibroblast growth factor receptor 3
inhibitor
Humans
AFibroblast growth factor receptor 4
inhibitor
Humans
URET proto-oncogene
substrate
Humans
UMacrophage colony-stimulating factor 1 receptor
substrate
Humans
UPlatelet-derived growth factor receptor alpha
substrate
Humans
UPlatelet-derived growth factor receptor beta
substrate
Humans
UMast/stem cell growth factor receptor Kit
substrate
Humans
UVascular endothelial growth factor receptor 2
substrate
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Following administration of erdafitinib 8 mg once daily, the mean (coefficient of variation [CV%]) steady-state maximum observed plasma concentration (Cmax), area under the curve (AUCtau), and minimum observed plasma concentration (Cmin) were 1,399 ng/mL (51%), 29,268 ng·h/mL (60%), and 936 ng/mL (65%), respectively Label.

Following single and repeat once daily dosing, erdafitinib exposure (maximum observed plasma concentration [Cmax] and area under the plasma concentration time curve [AUC]) increased proportionally across the dose range of 0.5 to 12 mg (0.06 to 1.3 times the maximum approved recommended dose) Label. Steady state was achieved after 2 weeks with once daily dosing and the mean accumulation ratio was 4-fold Label.

The median time to achieve peak plasma concentration (tmax) was 2.5 hours (range: 2 to 6 hours) Label. And finally, no clinically meaningful differences with erdafitinib pharmacokinetics were observed following administration of a high-fat and high-calorie meal (800 calories to 1,000 calories with approximately 50% of total caloric content of the meal from fat) in healthy subjects Label.

Volume of distribution

The mean apparent volume of distribution determined for erdafitinib is about 26 to 29 L in patients Label3.

Protein binding

The protein binding recorded for erdafitinib is approximately 99.8%, and it was determined to be primarily bound to alpha-1-acid glycoprotein Label.

Metabolism

It has been determined that erdafitinib is primarily metabolized by the cytochrome CYP2C9 and CYP3A4 isoenzymes Label. The contribution of CYP2C9 and CYP3A4 in the total clearance of erdafitinib is estimated to be 39% and 20% respectively Label. Unchanged erdafitinib was ultimately the predominant drug-related moiety found in the plasma - there were no circulating metabolites observed Label.

Route of elimination

After administering a single oral dose of radiolabeled erdafitinib, about 69% of the dose was recovered in feces (19% as unchanged) and 19% in urine (13% as unchanged) Label.

Half life

The mean effective half-life documented for erdafitinib is 59 hours Label, although it has also been observed between 50 to 60 hours 3.

Clearance

The mean total apparent clearance (CL/F) documented for erdafitinib is about 0.362 L/h Label, while the oral clearance has been observed to be approximately 0.26 L/h 3.

Toxicity

Based on the mechanism of action and findings in animal reproduction studies, erdafitinib can cause fetal harm when administered to a pregnant woman Label. There are no available data on erdafitinib use in pregnant women to inform a drug-associated risk Label. Oral administration of erdafitinib to pregnant rats during organogenesis caused malformations and embryo- fetal death at maternal exposures that were less than the human exposures at the maximum recommended human dose based on AUC Label. Advise pregnant women and females of reproductive potential of the potential risk to the fetus Label.

There are no data on the presence of erdafitinib in human milk, or the effects of erdafitinib on the breastfed child, or on milk production Label. Because of the potential for serious adverse reactions from erdafitinib in a breastfed child, advise lactating women not to breastfeed during treatment with erdafitinib and for one month following the last dose Label.

Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with erdafitinib Label.

Erdafitinib can cause fetal harm when administered to a pregnant woman Label. Advise females of reproductive potential to use effective contraception during treatment with erdafitinib and for one month after the last dose Label.

Advise male patients with female partners of reproductive potential to use effective contraception during treatment with erdafitinib and for one month after the last dose Label.

Based on findings from animal studies, erdafitinib may impair fertility in females of reproductive potential Label.

Safety and effectiveness of erdafitinib in pediatric patients have not been established Label.

No overall differences in safety or effectiveness were observed between these patients and younger patients in the use of erdafitinib Label.

Erdafitinib plasma concentrations were predicted to be higher in patients with the CYP2C93/3 genotype Label. Monitor for increased adverse reactions in patients who are known or suspected to have CYP2C93/3 genotype Label.

Carcinogenicity studies have not been conducted with erdafitinib Label.

Erdafitinib was not mutagenic in a bacterial reverse mutation (Ames) assay and was not clastogenic in an in vitro micronucleus or an in vivo rat bone marrow micronucleus assay Label.

Fertility studies in animals have not been conducted with erdafitinib. In the 3-month repeat-dose toxicity study, erdafitinib showed effects on female reproductive organs (necrosis of the ovarian corpora lutea) in rats at an exposure less than the human exposure (AUC) at maximum recommended human dose Label.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Erdafitinib can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Erdafitinib.
1alpha-Hydroxyvitamin D5The risk or severity of adverse effects can be increased when 1alpha-Hydroxyvitamin D5 is combined with Erdafitinib.
1alpha,24S-Dihydroxyvitamin D2The risk or severity of adverse effects can be increased when 1alpha,24S-Dihydroxyvitamin D2 is combined with Erdafitinib.
3,5-diiodothyropropionic acidThe therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Erdafitinib.
3,5-DiiodotyrosineThe therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Erdafitinib.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Erdafitinib.
5-androstenedioneThe metabolism of Erdafitinib can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Erdafitinib can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Erdafitinib can be decreased when combined with 6-O-benzylguanine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

General References
  1. 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:28965185]
  2. 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:28341788]
  3. Tabernero J, Bahleda R, Dienstmann R, Infante JR, Mita A, Italiano A, Calvo E, Moreno V, Adamo B, Gazzah A, Zhong B, Platero SJ, Smit JW, Stuyckens K, Chatterjee-Kishore M, Rodon J, Peddareddigari V, Luo FR, Soria JC: Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors. J Clin Oncol. 2015 Oct 20;33(30):3401-8. doi: 10.1200/JCO.2014.60.7341. Epub 2015 Aug 31. [PubMed:26324363]
  4. FDA grants accelerated approval to erdafitinib for metastatic urothelial carcinoma: Press Release [Link]
  5. First Targeted Therapy for Metastatic Bladder Cancer Receives FDA Approval [Link]
  6. Cayman Chemical Erdafitinib MSDS [File]
  7. NHS Evidence Briefing On: Erdafitinib capsules for metastatic or surgically unresectable urothelial cancer with FGFR gene aberrations – second line therapy [File]
External Links
PubChem Compound
67462786
PubChem Substance
347828443
ChemSpider
35308353
ChEMBL
CHEMBL3545376
HET
5SF
Wikipedia
Erdafitinib
PDB Entries
5ew8
FDA label
Download (558 KB)
MSDS
Download (56.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1CompletedOtherHealthy Volunteers2
1CompletedTreatmentHealthy Volunteers2
1RecruitingOtherHepatic Impairment1
1RecruitingTreatmentMetastatic Breast Cancer (MBC)1
1RecruitingTreatmentNeoplasms1
1, 2CompletedTreatmentHepatocellular,Carcinoma1
1, 2RecruitingTreatmentRelapsed Refractory Multiple Myeloma1
1, 2RecruitingTreatmentTransitional Cell Carcinoma1
2Active Not RecruitingTreatmentUrothelial Cancer1
2Not Yet RecruitingTreatmentAdenocarcinoma, Prostate / Castration Levels of Testosterone / Castration-Resistant Prostate Carcinoma / Double-Negative Prostate Carcinoma / Metastatic Hormone Refractory Prostate Cancer / PSA Progression / Stage IV Prostate Cancer AJCC v8 / Stage IVA Prostate Cancer AJCC v8 / Stage IVB Prostate Cancer AJCC v81
2RecruitingScreeningAdvanced Malignant Solid Neoplasm / Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma / Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma / Childhood Langerhans Cell Histiocytosis / Histiocytic Sarcoma (HS) / Juvenile Xanthogranuloma / Langerhans Cell Histiocytosis (LCH) / Malignant Gliomas / Malignant Lymphomas / Recurrent Central Nervous System Neoplasm / Recurrent Childhood Ependymoma / Recurrent Childhood Malignant Germ Cell Tumor / Recurrent Childhood Medulloblastoma / Recurrent Childhood Non-Hodgkin Lymphoma / Recurrent Childhood Rhabdomyosarcoma / Recurrent Childhood Soft Tissue Sarcoma / Recurrent Ewing Sarcoma / Recurrent Gliomas / Recurrent Hepatoblastoma / Recurrent Langerhans Cell Histiocytosis / Recurrent Malignant Solid Neoplasm / Recurrent Neuroblastoma / Recurrent Osteosarcoma / Recurrent Peripheral Primitive Neuroectodermal Tumor / Recurrent Rhabdoid Tumor / Refractory Central Nervous System Neoplasm / Refractory Childhood Malignant Germ Cell Tumor / Refractory Ewing Sarcoma / Refractory Glioma / Refractory Hepatoblastoma / Refractory Langerhans cell histiocytosis / Refractory Malignant Solid Neoplasm / Refractory Medulloblastoma / Refractory Neuroblastoma / Refractory Non-Hodgkin's lymphoma / Refractory Osteosarcoma / Refractory Peripheral Primitive Neuroectodermal Tumor / Refractory Rhabdoid Tumor / Refractory Rhabdomyosarcoma / Rhabdoid Tumors / Stage III Childhood Non-Hodgkin Lymphoma / Stage III Osteosarcoma / Stage III Osteosarcoma AJCC v7 / Stage III Soft Tissue Sarcoma / Stage III Soft Tissue Sarcoma AJCC v7 / Stage IV Childhood Non-Hodgkin Lymphoma / Stage IV Osteosarcoma / Stage IV Osteosarcoma AJCC v7 / Stage IV Soft Tissue Sarcoma / Stage IV Soft Tissue Sarcoma AJCC v7 / Stage IVA Osteosarcoma / Stage IVA Osteosarcoma AJCC v7 / Stage IVB Osteosarcoma / Stage IVB Osteosarcoma AJCC v7 / Wilms' tumor1
2RecruitingTreatmentAdvanced Malignant Neoplasm / Advanced Malignant Solid Neoplasm / Bladder Carcinoma / Carcinoma, Breast / Carcinoma, Colorectal / Carcinoma, Pancreatic / Cervical Carcinoma / Colon Carcinoma / Endometrial Carcinoma / Gastric Carcinoma / Gliomas / Head and Neck Carcinoma / Liver and Intrahepatic Bile Duct Carcinoma / Lung, Carcinoma / Malignant Lymphomas / Malignant Uterine Neoplasm / Melanoma / Oesophageal Carcinoma / Ovarian Carcinoma / Plasma Cell Myeloma / Prostate Cancer / Rectal Carcinoma / Recurrent Bladder Carcinoma / Recurrent Breast Carcinoma / Recurrent Cervical Carcinoma / Recurrent Colon Carcinoma / Recurrent Colorectal Carcinoma / Recurrent Esophageal Carcinoma / Recurrent Gastric Carcinoma / Recurrent Gliomas / Recurrent Head and Neck Carcinoma / Recurrent Liver Carcinoma / Recurrent Lung Carcinoma / Recurrent Lymphoma / Recurrent Malignant Solid Neoplasm / Recurrent Melanoma / Recurrent Ovarian Carcinoma / Recurrent Pancreatic Carcinoma / Recurrent Plasma Cell Myeloma / Recurrent Prostate Carcinoma / Recurrent Rectal Carcinoma / Recurrent Skin Carcinoma / Recurrent Solid Neoplasm / Recurrent Thyroid Gland Carcinoma / Recurrent Uterine Corpus Carcinoma / Refractory Lymphomas / Refractory Malignant Neoplasm / Refractory Malignant Solid Neoplasm / Refractory Plasma Cell Myeloma / Renal Carcinoma / Skin Carcinoma / Solid Neoplasms / Thyroid Gland Carcinoma / Uterine Corpus Cancer1
2RecruitingTreatmentAdvanced Malignant Solid Neoplasm / Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma / Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma / FGFR1 Gene Mutation / FGFR2 Gene Mutation / FGFR3 Gene Mutation / FGFR4 Gene Mutation / Histiocytosis / Low Grade Glioma (LGG) / Malignant Gliomas / Recurrent Central Nervous System Neoplasm / Recurrent Childhood Ependymoma / Recurrent Childhood Malignant Germ Cell Tumor / Recurrent Childhood Medulloblastoma / Recurrent Childhood Non-Hodgkin Lymphoma / Recurrent Childhood Rhabdomyosarcoma / Recurrent Childhood Soft Tissue Sarcoma / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Hepatoblastoma / Recurrent Langerhans Cell Histiocytosis / Recurrent Malignant Solid Neoplasm / Recurrent Neuroblastoma / Recurrent Osteosarcoma / Refractory Central Nervous System Neoplasm / Refractory Langerhans cell histiocytosis / Refractory Malignant Solid Neoplasm / Refractory Neuroblastoma / Refractory Non-Hodgkin's lymphoma / Rhabdoid Tumors / Stage III Childhood Non-Hodgkin Lymphoma / Stage III Soft Tissue Sarcoma AJCC v7 / Stage IV Childhood Non-Hodgkin Lymphoma / Stage IV Soft Tissue Sarcoma AJCC v7 / Wilms' tumor1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers / NSCLC Stage IV / Pulmonary Neoplasms / Squamous Cell Carcinoma of Lung1
2RecruitingTreatmentMultiple Myeloma (MM) / Relapsed/Refractory1
2RecruitingTreatmentNeoplasms / Tumor or Lymphoma1
3RecruitingTreatmentUrothelial Cancer1
Not AvailableApproved for MarketingNot AvailableAdvanced Cancers and FGFR Genetic Alterations1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral3 mg/1
Tablet, film coatedOral4 mg/1
Tablet, film coatedOral5 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9464071No2016-10-112031-04-28Us
US9902714No2018-02-272035-03-26Us
US8895601No2014-11-252031-05-22Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility<1 mg/mLMSDS
Predicted Properties
PropertyValueSource
Water Solubility0.013 mg/mLALOGPS
logP3.57ALOGPS
logP3.52ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)9.72ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area77.33 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity139.32 m3·mol-1ChemAxon
Polarizability51 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as alkyldiarylamines. These are tertiary alkylarylamines having two aryl and one alkyl groups attached to the amino group.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Alkyldiarylamines
Alternative Parents
Quinoxalines / Dimethoxybenzenes / Methoxyanilines / Aminophenyl ethers / Phenoxy compounds / Anisoles / Alkyl aryl ethers / Pyrazines / Pyrazoles / Heteroaromatic compounds
show 4 more
Substituents
Alkyldiarylamine / Diazanaphthalene / Quinoxaline / Dimethoxybenzene / M-dimethoxybenzene / Aminophenyl ether / Methoxyaniline / Phenoxy compound / Phenol ether / Aniline or substituted anilines
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation ...
Gene Name
FGFR1
Uniprot ID
P11362
Uniprot Name
Fibroblast growth factor receptor 1
Molecular Weight
91866.935 Da
References
  1. 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:28965185]
  2. Tabernero J, Bahleda R, Dienstmann R, Infante JR, Mita A, Italiano A, Calvo E, Moreno V, Adamo B, Gazzah A, Zhong B, Platero SJ, Smit JW, Stuyckens K, Chatterjee-Kishore M, Rodon J, Peddareddigari V, Luo FR, Soria JC: Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors. J Clin Oncol. 2015 Oct 20;33(30):3401-8. doi: 10.1200/JCO.2014.60.7341. Epub 2015 Aug 31. [PubMed:26324363]
  3. Erdafitinib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosi...
Gene Name
FGFR2
Uniprot ID
P21802
Uniprot Name
Fibroblast growth factor receptor 2
Molecular Weight
92024.29 Da
References
  1. 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:28965185]
  2. Tabernero J, Bahleda R, Dienstmann R, Infante JR, Mita A, Italiano A, Calvo E, Moreno V, Adamo B, Gazzah A, Zhong B, Platero SJ, Smit JW, Stuyckens K, Chatterjee-Kishore M, Rodon J, Peddareddigari V, Luo FR, Soria JC: Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors. J Clin Oncol. 2015 Oct 20;33(30):3401-8. doi: 10.1200/JCO.2014.60.7341. Epub 2015 Aug 31. [PubMed:26324363]
  3. Erdafitinib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an...
Gene Name
FGFR3
Uniprot ID
P22607
Uniprot Name
Fibroblast growth factor receptor 3
Molecular Weight
87708.905 Da
References
  1. 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:28965185]
  2. Tabernero J, Bahleda R, Dienstmann R, Infante JR, Mita A, Italiano A, Calvo E, Moreno V, Adamo B, Gazzah A, Zhong B, Platero SJ, Smit JW, Stuyckens K, Chatterjee-Kishore M, Rodon J, Peddareddigari V, Luo FR, Soria JC: Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors. J Clin Oncol. 2015 Oct 20;33(30):3401-8. doi: 10.1200/JCO.2014.60.7341. Epub 2015 Aug 31. [PubMed:26324363]
  3. Erdafitinib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation o...
Gene Name
FGFR4
Uniprot ID
P22455
Uniprot Name
Fibroblast growth factor receptor 4
Molecular Weight
87953.535 Da
References
  1. 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:28965185]
  2. Tabernero J, Bahleda R, Dienstmann R, Infante JR, Mita A, Italiano A, Calvo E, Moreno V, Adamo B, Gazzah A, Zhong B, Platero SJ, Smit JW, Stuyckens K, Chatterjee-Kishore M, Rodon J, Peddareddigari V, Luo FR, Soria JC: Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors. J Clin Oncol. 2015 Oct 20;33(30):3401-8. doi: 10.1200/JCO.2014.60.7341. Epub 2015 Aug 31. [PubMed:26324363]
  3. Erdafitinib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Not Available
Specific Function
Not Available
Gene Name
RET
Uniprot ID
O43519
Uniprot Name
RET proto-oncogene
Molecular Weight
2129.3 Da
References
  1. Erdafitinib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor ...
Gene Name
CSF1R
Uniprot ID
P07333
Uniprot Name
Macrophage colony-stimulating factor 1 receptor
Molecular Weight
107982.955 Da
References
  1. Erdafitinib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
Gene Name
PDGFRA
Uniprot ID
P16234
Uniprot Name
Platelet-derived growth factor receptor alpha
Molecular Weight
122668.46 Da
References
  1. Erdafitinib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vascular endothelial growth factor binding
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
Molecular Weight
123966.895 Da
References
  1. Erdafitinib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
Molecular Weight
109863.655 Da
References
  1. Erdafitinib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Erdafitinib FDA Label [File]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Erdafitinib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Erdafitinib FDA Label [File]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Erdafitinib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Erdafitinib FDA Label [File]

Drug created on October 20, 2016 15:28 / Updated on July 13, 2019 00:58