Compounds > pf-670462
Page last updated: 2024-11-13

pf-670462

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

PF-670462: inhibitor of casein kinase I epsilon; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

PF-670462 : A hydrochloride salt resulting from the formal reaction of 3-[(3-chlorophenoxy)methyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine with 2 mol eq. of hydrogen chloride. It is a selective inhibitor of the delta- and epsilon-isoforms of casein kinase 1 (CK1delta and CK1epsilon). [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID51049607
CHEMBL ID4643847
CHEBI ID87236
SCHEMBL ID18921552
MeSH IDM0513566

Synonyms (40)

Synonym
4-[1-cyclohexyl-4-(4-fluorophenyl)-1h-imidazol-5-yl]-2-pyrimidinamine dihydrochloride
BCP9000015
950912-80-8
HY-15490
FT-0673653
pf 670462
BCP0726000078
pf670462/ pf-670462
pf-670462
4-[1-cyclohexyl-4-(4-fluorophenyl)-1h-imidazol-5-yl]-2-pyrimidinaminedihydrochloride
2-pyrimidinamine, 4-(1-cyclohexyl-4-(4-fluorophenyl)-1h-imidazol-5-yl)-, hydrochloride (1:2)
D68ANS5I8B ,
4-(1-cyclohexyl-4-(4-fluorophenyl)-1h-imidazol-5-yl)pyrimidin-2-amine dihydrochloride
unii-d68ans5i8b
4-[3-cyclohexyl-5-(4-fluorophenyl)imidazol-4-yl]pyrimidin-2-amine dihydrochloride
pf670462
4-[1-cyclohexyl-4-(4-fluorophenyl)- 1h-imidazol-5-yl]-2-pyrimidinamine dihydrochloride
HB2170
c19h20fn5.2hcl
4-[1-cyclohexyl-4-(4-fluorophenyl)-1h-imidazol-5-yl]pyrimidin-2-amine dihydrochloride
CHEBI:87236
AC-32583
AKOS024457546
4-[3-cyclohexyl-5-(4-fluorophenyl)imidazol-4-yl]pyrimidin-2-amine;dihydrochloride
J-514222
4-[1-cyclohexyl-4-(4-fluorophenyl)-1h-imidazol-5-yl]pyrimidin-2-amine--hydrogen chloride (1/2)
DTXSID50679609
SCHEMBL18921552
AS-73728
BCP04305
Q27159459
pf-670462 hcl
950912-80-8 (hcl)
pf670462 dihydrochloride
mfcd12828759
EX-A2193
C77282
pf-670462 hydrochloride
S6734
CHEMBL4643847

Research Excerpts

Dosage Studied

The magnitude of the shifts in activity onsets achieved with chronic dosing of PF-670462 appears to be a function of the dose and the previously established phase relationship. The inhibition of CK1ε/δ was dose-dependently decreased, and at a higher dosage prevented the alcohol deprivation effect.

ExcerptRelevanceReference
" PF-670462 produced robust phase delays when dosed at circadian time (CT)9 (-1."( An inhibitor of casein kinase I epsilon induces phase delays in circadian rhythms under free-running and entrained conditions.
Adamowicz, W; Adams, J; Badura, L; Cianfrogna, J; Fisher, K; Holland, J; Kleiman, R; Nelson, F; Reynolds, L; Schaeffer, E; Sprouse, J; St Germain, K; Swanson, T; Tate, B, 2007)		1.25
" Dosing at ZT11 yielded more robust delays than dosing at ZT6 in keeping with earlier phase-response analyses with this agent."( Chronic treatment with a selective inhibitor of casein kinase I delta/epsilon yields cumulative phase delays in circadian rhythms.
Kleiman, R; Pickard, GE; Reynolds, L; Sprouse, J; Swanson, TA; Tate, B, 2010)		0.36
"The magnitude of the shifts in activity onsets achieved with chronic dosing of PF-670462 appears to be a function of the dose and the previously established phase relationship."( Chronic treatment with a selective inhibitor of casein kinase I delta/epsilon yields cumulative phase delays in circadian rhythms.
Kleiman, R; Pickard, GE; Reynolds, L; Sprouse, J; Swanson, TA; Tate, B, 2010)		0.59
" The inhibition of CK1ε/δ with systemic PF-670462 (0, 10, and 30 mg/kg) injections dose-dependently decreased, and at a higher dosage prevented the alcohol deprivation effect, as compared with vehicle-treated rats."( Inhibition of the casein-kinase-1-ε/δ/ prevents relapse-like alcohol drinking.
Corsi, MA; Corti, C; Merlo-Pich, EV; Noori, HR; Perreau-Lenz, S; Spanagel, R; Vengeliene, V, 2012)		0.65
" To circumvent such large interindividual variations, we developed an adaptive chronotherapeutics to identify precise dosing regimens that could restore normal circadian phase under different conditions."( Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy.
Chang, C; Chen, X; DeMarco, GJ; Doran, AC; Gaudreault, F; Kim, DW; Kim, JK; Wager, T, 2019)		0.51
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitorAn EC 2.7.11.* (protein-serine/threonine kinase) inhibitor that interferes with the action of non-specific serine/threonine protein kinase (EC 2.7.11.1), a kinase enzyme involved in phosphorylation of hydroxy group of serine or threonine.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
hydrochlorideA salt formally resulting from the reaction of hydrochloric acid with an organic base.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Casein kinase 1, delta tv1Sus scrofa (pig)IC50 (µMol)0.00770.00770.00770.0077AID1658379
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (1)

Assay IDTitleYearJournalArticle
AID1658379Inhibition of porcine brain CK-1delta using RRKHAAIGpSAYSITA peptide as substrate incubated for 30 mins in presence of [gamma-33P]-ATP by scintillation counting method2020ACS medicinal chemistry letters, Jun-11, Volume: 11, Issue:6
Scaffold Repurposing of in-House Chemical Library toward the Identification of New Casein Kinase 1 δ Inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (27)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's4 (14.81)29.6817
2010's21 (77.78)24.3611
2020's2 (7.41)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 25.00

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index25.00 (24.57)
Research Supply Index3.33 (2.92)
Research Growth Index4.98 (4.65)
Search Engine Demand Index26.69 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (25.00)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other27 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
gamma-aminobutyric acid
gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.. gamma-aminobutyric acid : A gamma-amino acid that is butanoic acid with the amino substituent located at C-4.		2.1310amino acid zwitterion;
gamma-amino acid;
monocarboxylic acid		human metabolite;
neurotransmitter;
Saccharomyces cerevisiae metabolite;
signalling molecule
adenine
[no description available]		2.17106-aminopurines;
purine nucleobase		Daphnia magna metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
phloroglucinol
Phloroglucinol: A trinitrobenzene derivative with antispasmodic properties that is used primarily as a laboratory reagent.. phloroglucinol : A benzenetriol with hydroxy groups at position 1, 3 and 5.		2.0610benzenetriol;
phenolic donor		algal metabolite
gabapentin
Gabapentin: A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of PARTIAL SEIZURES; NEURALGIA; and RESTLESS LEGS SYNDROME.. gabapentin : A gamma-amino acid that is cyclohexane substituted at position 1 by aminomethyl and carboxymethyl groups. Used for treatment of neuropathic pain and restless legs syndrome.		2.1310gamma-amino acidanticonvulsant;
calcium channel blocker;
environmental contaminant;
xenobiotic
corticosterone
[no description available]		2.111011beta-hydroxy steroid;
20-oxo steroid;
21-hydroxy steroid;
3-oxo-Delta(4) steroid;
C21-steroid;
glucocorticoid;
primary alpha-hydroxy ketone		human metabolite;
mouse metabolite
methamphetamine
Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.. methamphetamine : A member of the class of amphetamines in which the amino group of (S)-amphetamine carries a methyl substituent.		2.0510amphetamines;
secondary amine		central nervous system stimulant;
environmental contaminant;
neurotoxin;
psychotropic drug;
xenobiotic
oxytocin
Oxytocin: A nonapeptide hormone released from the neurohypophysis (PITUITARY GLAND, POSTERIOR). It differs from VASOPRESSIN by two amino acids at residues 3 and 8. Oxytocin acts on SMOOTH MUSCLE CELLS, such as causing UTERINE CONTRACTIONS and MILK EJECTION.. oxytocin : A cyclic nonapeptide hormone with amino acid sequence CYIQNCPLG that also acts as a neurotransmitter in the brain; the principal uterine-contracting and milk-ejecting hormone of the posterior pituitary. Together with the neuropeptide vasopressin, it is believed to influence social cognition and behaviour.		2.1710heterodetic cyclic peptide;
peptide hormone		oxytocic;
vasodilator agent
ic 261
IC 261: a caseine kinase-1 inhibitor; structure in first source		2.0610
tetrodotoxin
Tetrodotoxin: An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.. tetrodotoxin : A quinazoline alkaloid that is a marine toxin isolated from fish such as puffer fish. It has been shown to exhibit potential neutotoxicity due to its ability to block voltage-gated sodium channels.		2.1310azatetracycloalkane;
oxatetracycloalkane;
quinazoline alkaloid		animal metabolite;
bacterial metabolite;
marine metabolite;
neurotoxin;
voltage-gated sodium channel blocker
knk 437
KNK 437: inhibits thermotolerance acquisition and heat shock protein induction in colon carcinoma cells; structure in first source		2.1310
beta-endorphin
beta-Endorphin: A 31-amino acid peptide that is the C-terminal fragment of BETA-LIPOTROPIN. It acts on OPIOID RECEPTORS and is an analgesic. Its first four amino acids at the N-terminal are identical to the tetrapeptide sequence of METHIONINE ENKEPHALIN and LEUCINE ENKEPHALIN.. beta-endorphin : A polypeptide consisting of 31 amino acid residues in the sequence Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu. It is an endogenous opioid peptide neurotransmitter found in the neurons of both the central and peripheral nervous system and results from processing of the precursor protein proopiomelanocortin (POMC).		2.1710
pci 32765
ibrutinib: a Btk protein inhibitor. ibrutinib : A member of the class of acrylamides that is (3R)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine in which the piperidine nitrogen is replaced by an acryloyl group. A selective and covalent inhibitor of the enzyme Bruton's tyrosine kinase, it is used for treatment of B-cell malignancies.		2.1710acrylamides;
aromatic amine;
aromatic ether;
N-acylpiperidine;
pyrazolopyrimidine;
tertiary carboxamide		antineoplastic agent;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor
neurotensin
neurotensin, Tyr(11)-: RN given refers to parent cpd & (D)-isomer; RN for cpd without isomeric designation not avail 5/91		2.1710peptide hormonehuman metabolite;
mitogen;
neurotransmitter;
vulnerary
piperidines
Piperidines: A family of hexahydropyridines.		2.1710
ConditionIndicatedRelationship StrengthStudiesTrials
Anaphylactic Reaction
[description not available]		02.5720
Canine Diseases
[description not available]		02.2110
Anaphylaxis
An acute hypersensitivity reaction due to exposure to a previously encountered ANTIGEN. The reaction may include rapidly progressing URTICARIA, respiratory distress, vascular collapse, systemic SHOCK, and death.		02.5720
B-Cell Chronic Lymphocytic Leukemia
[description not available]		02.1710
Leukemia, Lymphocytic, Chronic, B-Cell
A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.		02.1710
Colitis Gravis
[description not available]		02.1710
Colitis, Ulcerative
Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.		02.1710
Nycturia
[description not available]		02.2110
Nocturia
Frequent URINATION at night that interrupts sleep. It is often associated with outflow obstruction, DIABETES MELLITUS, or bladder inflammation (CYSTITIS).		02.2110
Acute Confusional Senile Dementia
[description not available]		02.2110
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.2110
Age-Related Memory Disorders
[description not available]		02.2110
Nerve Degeneration
Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.		02.2110
Long Sleeper Syndrome
[description not available]		02.2110
Alzheimer Disease
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)		02.2110
Memory Disorders
Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.		02.2110
Sleep Wake Disorders
Abnormal sleep-wake schedule or pattern associated with the CIRCADIAN RHYTHM which affect the length, timing, and/or rigidity of the sleep-wake cycle relative to the day-night cycle.		02.2110
Allergic Rhinitis
[description not available]		02.1310
Rhinitis, Allergic
An inflammation of the NASAL MUCOSA triggered by ALLERGENS.		02.1310
Benign Neoplasms
[description not available]		02.0610
Neoplasms
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.		02.0610
Alcohol Abuse
[description not available]		02.0710
Alcohol Drinking
Behaviors associated with the ingesting of ALCOHOLIC BEVERAGES, including social drinking.		02.0710
Alcoholism
A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4)		02.0710