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

Identification

Generic Name
Rimtuzalcap
DrugBank Accession Number
DB16733
Background

Rimtuzalcap is a novel modulator of small-conductance calcium-activated potassium channels that is under investigation for the treatment of essential tremor.3

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 378.428
Monoisotopic: 378.197965743
Chemical Formula
C18H24F2N6O
Synonyms
  • Rimtuzalcap
External IDs
  • CAD-1883
  • WHO 11140

Pharmacology

Indication

Not Available

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Rimtuzalcap is thought to decrease the firing of neurons in the olivo-cerebellar network which are theorized to contribute to the dysfunction of oscillatory neuronal input to the motor cortex that results in the presentation of motor tremors in the typical 4-12 Hz band associated with essential tremor.1,3 Inhibition of this dysfunctional firing may provide benefit to patients with essential tremor.

Mechanism of action

Rimtuzalcap is a positive allosteric modulator of small-conductance calcium-activated K+ channels (SK channels). 3 It is thought to exert its activity on essential tremor through increasing SK channel activity in the Purkinje cells of the cerebellar cortex resulting in hyperpolarization and consequently, a slower firing rate.2 These Purkinje cells have a glutamatergic excitatory input to deep cerebellar neurons in the dentate nucleus which themselves exert the same input on the ventral intermediate nucleus in the thalamocortical system.1 From there the ventral intermediate nucleus exerts excitatory input to the motor cortex, producing an effect on motor function. It is the decrease in the activity of this pathway through targeting Purkinje cell firing rate that is thought to have a beneficial impact on essential tremor.

TargetActionsOrganism
ASmall conductance calcium-activated potassium channel protein 1
positive allosteric modulator
Humans
ASmall conductance calcium-activated potassium channel protein 2
positive allosteric modulator
Humans
USmall conductance calcium-activated potassium channel protein 3
positive allosteric modulator
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
Not Available
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
USO2D5J77R
CAS number
2167246-24-2
InChI Key
OVLIDRAJVMUEMC-UHFFFAOYSA-N
InChI
InChI=1S/C18H24F2N6O/c1-13-4-7-26(24-13)17-22-15(21-14-2-5-18(19,20)6-3-14)12-16(23-17)25-8-10-27-11-9-25/h4,7,12,14H,2-3,5-6,8-11H2,1H3,(H,21,22,23)
IUPAC Name
N-(4,4-difluorocyclohexyl)-2-(3-methyl-1H-pyrazol-1-yl)-6-(morpholin-4-yl)pyrimidin-4-amine
SMILES
CC1=NN(C=C1)C1=NC(NC2CCC(F)(F)CC2)=CC(=N1)N1CCOCC1

References

General References
  1. Zhang X, Santaniello S: Role of cerebellar GABAergic dysfunctions in the origins of essential tremor. Proc Natl Acad Sci U S A. 2019 Jul 2;116(27):13592-13601. doi: 10.1073/pnas.1817689116. Epub 2019 Jun 17. [Article]
  2. Hosy E, Piochon C, Teuling E, Rinaldo L, Hansel C: SK2 channel expression and function in cerebellar Purkinje cells. J Physiol. 2011 Jul 15;589(Pt 14):3433-40. doi: 10.1113/jphysiol.2011.205823. Epub 2011 Apr 26. [Article]
  3. Clinical Trial: NCT03688685 [Link]
ChemSpider
81367401

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentEssential Tremor1
2WithdrawnTreatmentARCA1 - Autosomal Recessive Cerebellar Ataxia Type 1 / Spinocerebellar Ataxia 3 / Spinocerebellar Ataxia Type 1 / Spinocerebellar Ataxia Type 10 / Spinocerebellar Ataxia Type 17 / Spinocerebellar Ataxia Type 6 / Spinocerebellar Ataxia Type 7 / Spinocerebellar Ataxia Type 8 / Spinocerebellar Ataxias Type 2 / Spinocerebellar Atrophy (SCA)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 Solubility0.561 mg/mLALOGPS
logP3.1ALOGPS
logP2.78Chemaxon
logS-2.8ALOGPS
pKa (Strongest Basic)3.72Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area68.1 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity101.56 m3·mol-1Chemaxon
Polarizability39.18 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
General Function
Small conductance calcium-activated potassium channel activity
Specific Function
Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to ...
Gene Name
KCNN1
Uniprot ID
Q92952
Uniprot Name
Small conductance calcium-activated potassium channel protein 1
Molecular Weight
59986.87 Da
References
  1. Clinical Trial: NCT03688685 [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
General Function
Small conductance calcium-activated potassium channel activity
Specific Function
Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to ...
Gene Name
KCNN2
Uniprot ID
Q9H2S1
Uniprot Name
Small conductance calcium-activated potassium channel protein 2
Molecular Weight
63759.03 Da
References
  1. Clinical Trial: NCT03688685 [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Positive allosteric modulator
General Function
Small conductance calcium-activated potassium channel activity
Specific Function
Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to ...
Gene Name
KCNN3
Uniprot ID
Q9UGI6
Uniprot Name
Small conductance calcium-activated potassium channel protein 3
Molecular Weight
82025.305 Da
References
  1. Clinical Trial: NCT03688685 [Link]

Drug created at September 21, 2021 20:50 / Updated at September 25, 2021 23:52