Defactinib

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Generic Name
Defactinib
DrugBank Accession Number
DB12282
Background

Defactinib has been investigated for the treatment of Malignant Pleural Mesothelioma.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 510.5
Monoisotopic: 510.140942231
Chemical Formula
C20H21F3N8O3S
Synonyms
  • Defactinib
  • N-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide
External IDs
  • PF-04554878
  • VS-6063

Pharmacology

Indication

Not Available

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action
TargetActionsOrganism
AFocal adhesion kinase 1
inhibitor
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

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Products

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Product Ingredients
IngredientUNIICASInChI Key
Defactinib HydrochlorideL2S469LM491073160-26-5RCHQNUQAHJNRBY-UHFFFAOYSA-N

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzamides. These are organic compounds containing a carboxamido substituent attached to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
Benzamides
Alternative Parents
Aniline and substituted anilines / Benzoyl derivatives / Aminopyrimidines and derivatives / Secondary alkylarylamines / Pyrazines / Organosulfonamides / Imidolactams / Organic sulfonamides / Heteroaromatic compounds / Aminosulfonyl compounds
show 9 more
Substituents
Alkyl fluoride / Alkyl halide / Amine / Amino acid or derivatives / Aminopyrimidine / Aminosulfonyl compound / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Azacycle / Benzamide
show 26 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
53O87HA2QU
CAS number
1073154-85-4
InChI Key
FWLMVFUGMHIOAA-UHFFFAOYSA-N
InChI
InChI=1S/C20H21F3N8O3S/c1-24-18(32)12-4-6-13(7-5-12)29-19-28-10-14(20(21,22)23)16(30-19)27-11-15-17(26-9-8-25-15)31(2)35(3,33)34/h4-10H,11H2,1-3H3,(H,24,32)(H2,27,28,29,30)
IUPAC Name
N-methyl-4-{[4-({[3-(N-methylmethanesulfonamido)pyrazin-2-yl]methyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzamide
SMILES
CNC(=O)C1=CC=C(NC2=NC=C(C(NCC3=C(N=CC=N3)N(C)S(C)(=O)=O)=N2)C(F)(F)F)C=C1

References

General References
Not Available
Human Metabolome Database
HMDB0250931
PubChem Compound
25117126
PubChem Substance
347828550
ChemSpider
32695161
BindingDB
418817
ChEMBL
CHEMBL3137331
ZINC
ZINC000103297739
PDBe Ligand
7KD
Wikipedia
Defactinib
PDB Entries
5mah

Clinical Trials

Clinical Trials
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PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
3RecruitingTreatmentLow Grade Serous Ovarian Cancer1somestatusstop reasonjust information to hide
2Active Not RecruitingScreeningAdvanced Lymphomas / Advanced Malignant Solid Tumor / Bladder Carcinoma / Breast Carcinoma / Carcinoma of the Head and Neck / Carcinoma of the Skin / Cervical Carcinoma / Colon Carcinoma / Colorectal Carcinoma (CRC) / Endometrial Carcinoma / Esophageal Carcinoma / Exocrine Pancreas Carcinoma / Gastric Carcinoma / Glioma / Hematopoietic and Lymphoid System Neoplasm / Hepatocellular Carcinoma / Lung Carcinoma / Lymphoma / Malignant Uterine Neoplasm / Melanoma / Multiple Myeloma (MM) / Ovarian Carcinoma / Prostate Carcinoma / 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 multiple myeloma / Recurrent Ovarian Carcinoma / Recurrent Pancreatic Carcinoma / Recurrent Prostate Carcinoma / Recurrent Rectal Carcinoma / Recurrent Skin Carcinoma / Recurrent Thyroid Gland Carcinoma / Recurrent Uterine Corpus Cancer / Refractory Lymphomas / Refractory Malignant Solid Neoplasm / Refractory Multiple Myeloma / Renal Carcinoma / Thyroid Gland Carcinoma / Uterine Corpus Cancer1somestatusstop reasonjust information to hide
2Active Not RecruitingTreatmentAdvanced Lymphomas / Advanced Malignant Solid Tumor / Hematopoietic and Lymphoid System Neoplasm / Refractory Lymphomas / Refractory Malignant Solid Neoplasm / Refractory Multiple Myeloma1somestatusstop reasonjust information to hide
2Active Not RecruitingTreatmentLow-grade Serous Ovarian Carcinoma (LGSOC) / Ovarian Cancer1somestatusstop reasonjust information to hide
2Active Not RecruitingTreatmentMetastatic Uveal Melanoma1somestatusstop reasonjust information to hide

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 Solubility0.0184 mg/mLALOGPS
logP2.39ALOGPS
logP0.75Chemaxon
logS-4.4ALOGPS
pKa (Strongest Acidic)12.63Chemaxon
pKa (Strongest Basic)4.03Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count9Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area142.1 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity123.28 m3·mol-1Chemaxon
Polarizability46.05 Å3Chemaxon
Number of Rings3Chemaxon
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/MSsplash10-01q9-0000980000-db633b28ea9212947c02
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-4000190000-411a80d6bc534597d2cf
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0adi-3736960000-830ef40f9bc2b47d5eab
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0f89-0000910000-eb16c00e5c91c7ec16d1
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0wu0-0201900000-da12bc93ec510245eb92
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9211000000-d90e8440da1e38be0363
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-202.33603
predicted
DeepCCS 1.0 (2019)
[M+H]+204.73158
predicted
DeepCCS 1.0 (2019)
[M+Na]+211.28456
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:9360983). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription
Specific Function
actin binding
Gene Name
PTK2
Uniprot ID
Q05397
Uniprot Name
Focal adhesion kinase 1
Molecular Weight
119232.025 Da
References
  1. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Drug created at October 20, 2016 21:49 / Updated at August 27, 2024 19:15