NAV

Talmapimod

Identification

Generic Name
Talmapimod
DrugBank Accession Number
DB05412
Background

Talmapimod is the first-generation oral p38 MAP kinase inhibitor developed by Scios. It has shown to be effective to cure inflammatory diseases such as Rheumatoid Arthritis.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 513.004
Monoisotopic: 512.199046758
Chemical Formula
C27H30ClFN4O3
Synonyms
  • Talmapimod
External IDs
  • SCIO-469
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Pharmacology

Indication

Investigated for use/treatment in pain (acute or chronic) and rheumatoid arthritis.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

SCIO-469 inhibits p38 kinase, a stimulatory modulator of pro-inflammatory factors including tumor necrosis factor-alpha (TNFa), interleukin-1 (IL-1), and cyclooxygenase-2 (COX-2), all of which are known to contribute to both symptoms and disease progression in patients with Rheumatoid Arthritis (RA). Existing protein-based products that antagonize TNFa have been shown to markedly relieve the symptoms and retard the progression of RA. It also has the potential for additional benefits associated with its inhibition of IL-1 and COX-2.

TargetActionsOrganism
UMitogen-activated protein kinase 14Not AvailableHumans
UTumor necrosis factorNot AvailableHumans
UInterleukin-1 betaNot AvailableHumans
UCytochrome c oxidase subunit 2Not AvailableHumans
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 Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as indolecarboxamides and derivatives. These are compounds containing a carboxamide group attached to an indole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Indolecarboxylic acids and derivatives
Direct Parent
Indolecarboxamides and derivatives
Alternative Parents
N-alkylindoles / Indoles / Benzylamines / Aryl ketones / Phenylmethylamines / Aralkylamines / N-alkylpiperazines / Fluorobenzenes / Aryl chlorides / Aryl fluorides
show 13 more
Substituents
1,4-diazinane / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Aryl chloride / Aryl fluoride / Aryl halide / Aryl ketone / Azacycle
show 34 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
B1E00KQ6NT
CAS number
309913-83-5
InChI Key
ZMELOYOKMZBMRB-DLBZAZTESA-N
InChI
InChI=1S/C27H30ClFN4O3/c1-16-13-33(17(2)12-32(16)14-18-6-8-19(29)9-7-18)26(35)21-10-20-22(25(34)27(36)30(3)4)15-31(5)24(20)11-23(21)28/h6-11,15-17H,12-14H2,1-5H3/t16-,17+/m0/s1
IUPAC Name
2-{6-chloro-5-[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethylpiperazine-1-carbonyl]-1-methyl-1H-indol-3-yl}-N,N-dimethyl-2-oxoacetamide
SMILES
[H][C@]1(C)CN(C(=O)C2=C(Cl)C=C3N(C)C=C(C(=O)C(=O)N(C)C)C3=C2)[C@]([H])(C)CN1CC1=CC=C(F)C=C1

References

General References
  1. Vanderkerken K, Medicherla S, Coulton L, De Raeve H, Willems A, Lawson M, Van Camp B, Protter AA, Higgins LS, Menu E, Croucher PI: Inhibition of p38alpha mitogen-activated protein kinase prevents the development of osteolytic bone disease, reduces tumor burden, and increases survival in murine models of multiple myeloma. Cancer Res. 2007 May 15;67(10):4572-7. Epub 2007 May 10. [Article]
  2. Nguyen AN, Stebbins EG, Henson M, O'Young G, Choi SJ, Quon D, Damm D, Reddy M, Ma JY, Haghnazari E, Kapoun AM, Medicherla S, Protter A, Schreiner GF, Kurihara N, Anderson J, Roodman GD, Navas TA, Higgins LS: Normalizing the bone marrow microenvironment with p38 inhibitor reduces multiple myeloma cell proliferation and adhesion and suppresses osteoclast formation. Exp Cell Res. 2006 Jun 10;312(10):1909-23. Epub 2006 Apr 4. [Article]
PubChem Compound
9871074
PubChem Substance
347827727
ChemSpider
8046764
BindingDB
50266947
ChEBI
90683
ChEMBL
CHEMBL514201
ZINC
ZINC000034001955
PDBe Ligand
469
PDB Entries
3hub / 3zsh

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
2CompletedTreatmentBone marrow disorder / Bone Marrow Neoplasms / Hematologic Disease and Disorders / Myelodysplastic Syndrome1
2CompletedTreatmentMultiple Myeloma (MM)2
2CompletedTreatmentRheumatoid Arthritis2
1CompletedTreatmentRheumatoid Arthritis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00586 mg/mLALOGPS
logP3.78ALOGPS
logP3.9Chemaxon
logS-4.9ALOGPS
pKa (Strongest Basic)6.49Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area65.86 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity139.25 m3·mol-1Chemaxon
Polarizability54.45 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
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/MSsplash10-03di-0010290000-19fb77c90073f7e5a0b0
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0001590000-4291342c1b18ea3b0bc9
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-01ox-3313940000-4df347aa7a2509451963
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-03kc-0912820000-00d20c3cbf404b519512
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03k9-0001920000-e51276f094967973fc64
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0bu0-2109300000-0db76eb4a2f78d9bfccf
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-226.37201
predicted
DeepCCS 1.0 (2019)
[M+H]+228.26743
predicted
DeepCCS 1.0 (2019)
[M+Na]+234.09518
predicted
DeepCCS 1.0 (2019)

Targets

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Details1. Mitogen-activated protein kinase 14
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellu...
Gene Name
MAPK14
Uniprot ID
Q16539
Uniprot Name
Mitogen-activated protein kinase 14
Molecular Weight
41292.885 Da
Details2. Tumor necrosis factor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Tumor necrosis factor receptor binding
Specific Function
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct ac...
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
Molecular Weight
25644.15 Da
Details3. Interleukin-1 beta
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein domain specific binding
Specific Function
Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, ...
Gene Name
IL1B
Uniprot ID
P01584
Uniprot Name
Interleukin-1 beta
Molecular Weight
30747.7 Da
Details4. Cytochrome c oxidase subunit 2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Cytochrome-c oxidase activity
Specific Function
Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Subunit 2 transfers the ...
Gene Name
MT-CO2
Uniprot ID
P00403
Uniprot Name
Cytochrome c oxidase subunit 2
Molecular Weight
25564.73 Da

Drug created at November 18, 2007 18:24 / Updated at February 21, 2021 18:51