CPI-1205

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

Identification

Generic Name
CPI-1205
DrugBank Accession Number
DB14581
Background

Potent and selective histone methyltransferase EZH2 inhibitor.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 518.581
Monoisotopic: 518.250475428
Chemical Formula
C27H33F3N4O3
Synonyms
Not Available
External IDs
  • CPI-1205

Pharmacology

Indication

Not Available

Reduce drug development failure rates
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Pharmacodynamics

Not Available

Mechanism of action
TargetActionsOrganism
AHistone-lysine N-methyltransferase EZH2
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

Categories

Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
455J2479FY
CAS number
1621862-70-1
InChI Key
HPODOLXTMDHLLC-QGZVFWFLSA-N
InChI
InChI=1S/C27H33F3N4O3/c1-16-13-23(37-4)21(25(35)32-16)14-31-26(36)24-18(3)34(22-8-6-5-7-20(22)24)17(2)19-9-11-33(12-10-19)15-27(28,29)30/h5-8,13,17,19H,9-12,14-15H2,1-4H3,(H,31,36)(H,32,35)/t17-/m1/s1
IUPAC Name
N-[(4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2-methyl-1-[(1R)-1-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]ethyl]-1H-indole-3-carboxamide
SMILES
COC1=C(CNC(=O)C2=C(C)N([C@H](C)C3CCN(CC(F)(F)F)CC3)C3=CC=CC=C23)C(=O)NC(C)=C1

References

General References
Not Available
ChemSpider
58540498
ZINC
ZINC000220982768

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAdvanced Solid Tumors1
1CompletedTreatmentB-Cell Lymphoma1
1, 2Active Not RecruitingTreatmentMetastatic Castration-Resistant Prostate Cancer (mCRPC)1

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 Solubility0.00741 mg/mLALOGPS
logP4.31ALOGPS
logP2.99Chemaxon
logS-4.8ALOGPS
pKa (Strongest Acidic)11.15Chemaxon
pKa (Strongest Basic)3.46Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area75.6 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity139.68 m3·mol-1Chemaxon
Polarizability53.15 Å3Chemaxon
Number of Rings4Chemaxon
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/MSsplash10-014i-0000190000-54e2ee0142d49cf18325
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0001290000-3681658c79405b416143
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0gi9-0209720000-ca72077882ec065ab560
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0uxv-0009650000-8ce24a484285c9350698
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0296-0903320000-e34e7e47ca88230a1615
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-05tf-4106930000-3a4e09f6bf290eb2a805
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2 (PubMed:22323599). Compared to EZH1-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA. Regulates the circadian clock via histone methylation at the promoter of the circadian genes. Essential for the CRY1/2-mediated repression of the transcriptional activation of PER1/2 by the CLOCK-ARNTL/BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-27' of histone H3 on PER1/2 promoters which is necessary for the CRY1/2 proteins to inhibit transcription.
Specific Function
Chromatin binding
Gene Name
EZH2
Uniprot ID
Q15910
Uniprot Name
Histone-lysine N-methyltransferase EZH2
Molecular Weight
85362.435 Da
References
  1. Vaswani RG, Gehling VS, Dakin LA, Cook AS, Nasveschuk CG, Duplessis M, Iyer P, Balasubramanian S, Zhao F, Good AC, Campbell R, Lee C, Cantone N, Cummings RT, Normant E, Bellon SF, Albrecht BK, Harmange JC, Trojer P, Audia JE, Zhang Y, Justin N, Chen S, Wilson JR, Gamblin SJ: Identification of (R)-N-((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1 -(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a Potent and Selective Inhibitor of Histone Methyltransferase EZH2, Suitable for Phase I Clinical Trials for B-Cell Lymphomas. J Med Chem. 2016 Nov 10;59(21):9928-9941. doi: 10.1021/acs.jmedchem.6b01315. Epub 2016 Oct 28. [Article]

Drug created at July 30, 2018 17:30 / Updated at June 12, 2020 16:53