Radotinib

Identification

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Name
Radotinib
Accession Number
DB12323
Type
Small Molecule
Groups
Investigational
Description

Radotinib is under investigation for the treatment of Leukemia, Myelogenous, Chronic, BCR-ABL Positive.

Structure
Thumb
Synonyms
  • Radotinib
External IDs
IY5511
Categories
UNII
I284LJY110
CAS number
926037-48-1
Weight
Average: 530.515
Monoisotopic: 530.179041817
Chemical Formula
C27H21F3N8O
InChI Key
DUPWHXBITIZIKZ-UHFFFAOYSA-N
InChI
InChI=1S/C27H21F3N8O/c1-16-3-4-18(9-23(16)37-26-33-6-5-22(36-26)24-13-31-7-8-32-24)25(39)35-20-10-19(27(28,29)30)11-21(12-20)38-14-17(2)34-15-38/h3-15H,1-2H3,(H,35,39)(H,33,36,37)
IUPAC Name
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-{[4-(pyrazin-2-yl)pyrimidin-2-yl]amino}benzamide
SMILES
CC1=CN(C=N1)C1=CC(NC(=O)C2=CC=C(C)C(NC3=NC=CC(=N3)C3=CN=CC=N3)=C2)=CC(=C1)C(F)(F)F

Pharmacology

Indication

Radotinib is indicated for the treatment of different types of cancer, most notably Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) with resistance or intolerance of other Bcr-Abl tyrosine-kinase inhibitors, such as patients resistant or intolerant to imatinib.

Pharmacodynamics
Not Available
Mechanism of action

Philadelphia chromosome positive (Ph+) leukemia is driven by the constitutive enzymatic activity of the BCR-ABL1 fusion kinase. Tyrosine kinase inhibitors (TKIs) that block the activity of BCR-ABL1 are successfully used clinically to treat chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

TargetActionsOrganism
ATyrosine-protein kinase ABL1
antagonist
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

radotinib shares the recently reported cardiovascular toxicity of nilotinib. Electrocardiographic abnormalities were recorded in 20% of all patients and some of them developed severe or even life-threatening coronary artery disease, QT prolongation, changes in left ventricular ejection fraction.

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

Interactions

Drug Interactions
DrugInteraction
3,5-diiodothyropropionic acidThe therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Radotinib.
3,5-DiiodotyrosineThe therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Radotinib.
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Radotinib.
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Radotinib.
BenzylthiouracilThe therapeutic efficacy of Benzylthiouracil can be decreased when used in combination with Radotinib.
CarbimazoleThe therapeutic efficacy of Carbimazole can be decreased when used in combination with Radotinib.
DibromotyrosineThe therapeutic efficacy of Dibromotyrosine can be decreased when used in combination with Radotinib.
ElcatoninThe therapeutic efficacy of Elcatonin can be decreased when used in combination with Radotinib.
FollitropinThe therapeutic efficacy of Follitropin can be decreased when used in combination with Radotinib.
LevothyroxineThe therapeutic efficacy of Levothyroxine can be decreased when used in combination with Radotinib.
Additional Data Available
  • Extended Description
    Extended Description

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

    Learn more
  • 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.

    Learn more
  • 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. Kim SH, Menon H, Jootar S, Saikia T, Kwak JY, Sohn SK, Park JS, Jeong SH, Kim HJ, Kim YK, Oh SJ, Kim H, Zang DY, Chung JS, Shin HJ, Do YR, Kim JA, Kim DY, Choi CW, Park S, Park HL, Lee GY, Cho DJ, Shin JS, Kim DW: Efficacy and safety of radotinib in chronic phase chronic myeloid leukemia patients with resistance or intolerance to BCR-ABL1 tyrosine kinase inhibitors. Haematologica. 2014 Jul;99(7):1191-6. doi: 10.3324/haematol.2013.096776. Epub 2014 Apr 4. [PubMed:24705186]
  2. O'Hare T, Zabriskie MS, Eiring AM, Deininger MW: Pushing the limits of targeted therapy in chronic myeloid leukaemia. Nat Rev Cancer. 2012 Jul 24;12(8):513-26. doi: 10.1038/nrc3317. [PubMed:22825216]
  3. Zabriskie MS, Vellore NA, Gantz KC, Deininger MW, O'Hare T: Radotinib is an effective inhibitor of native and kinase domain-mutant BCR-ABL1. Leukemia. 2015 Sep;29(9):1939-42. doi: 10.1038/leu.2015.42. Epub 2015 Feb 13. [PubMed:25676420]
External Links
PubChem Compound
16063245
PubChem Substance
347828586
ChemSpider
17222861
Wikipedia
Radotinib

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentHematologic Diseases / Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Leukemias / Myeloid Leukemias / Philadelphia Chromosome1
2RecruitingTreatmentChronic Myeloid Leukemia (CML)1
3CompletedTreatmentBone Marrow Diseases / Hematologic Diseases / Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Leukemias / Myeloid Leukemias / Philadelphia Chromosome1
3RecruitingTreatmentChronic Myeloid Leukemia, Chronic Phase1
Not AvailableWithdrawnNot AvailableLeukemia, Myelogenous, Chronic, BCR-ABL Positive1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00234 mg/mLALOGPS
logP3.77ALOGPS
logP4.53ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)12.22ChemAxon
pKa (Strongest Basic)6.29ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area110.51 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity150.32 m3·mol-1ChemAxon
Polarizability52.47 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
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 benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R', where R,R'= benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Benzanilides
Alternative Parents
Phenylimidazoles / Trifluoromethylbenzenes / Aminobenzoic acids and derivatives / p-Toluamides / Benzamides / Aniline and substituted anilines / Benzoyl derivatives / Aminopyrimidines and derivatives / Pyrazines / N-substituted imidazoles
show 10 more
Substituents
Benzanilide / 1-phenylimidazole / Aminobenzoic acid or derivatives / Trifluoromethylbenzene / Benzamide / Benzoic acid or derivatives / Toluamide / P-toluamide / Benzoyl / Aniline or substituted anilines
show 27 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Syntaxin binding
Specific Function
Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility a...
Gene Name
ABL1
Uniprot ID
P00519
Uniprot Name
Tyrosine-protein kinase ABL1
Molecular Weight
122871.435 Da
References
  1. Kim SH, Menon H, Jootar S, Saikia T, Kwak JY, Sohn SK, Park JS, Jeong SH, Kim HJ, Kim YK, Oh SJ, Kim H, Zang DY, Chung JS, Shin HJ, Do YR, Kim JA, Kim DY, Choi CW, Park S, Park HL, Lee GY, Cho DJ, Shin JS, Kim DW: Efficacy and safety of radotinib in chronic phase chronic myeloid leukemia patients with resistance or intolerance to BCR-ABL1 tyrosine kinase inhibitors. Haematologica. 2014 Jul;99(7):1191-6. doi: 10.3324/haematol.2013.096776. Epub 2014 Apr 4. [PubMed:24705186]

Drug created on October 20, 2016 15:57 / Updated on June 04, 2019 07:36