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Details

Stereochemistry ABSOLUTE
Molecular Formula C27H30ClFN4O3
Molecular Weight 513.004
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TALMAPIMOD

SMILES

C[C@H]1CN([C@H](C)CN1CC2=CC=C(F)C=C2)C(=O)C3=C(Cl)C=C4N(C)C=C(C(=O)C(=O)N(C)C)C4=C3

InChI

InChIKey=ZMELOYOKMZBMRB-DLBZAZTESA-N
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

HIDE SMILES / InChI

Molecular Formula C27H30ClFN4O3
Molecular Weight 513.004
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Talmapimod is a p38 MAPK kinase inhibitor that inhibits p38 alpha with IC50 value of 9 nM which is 10-times lower then IC50 for p38 beta. Talmapimod was under clinical development for the treatment of Myelodysplastic Syndromes, Multiple Myeloma and Rheumatoid Arthritis (phase II), however, it seems to be discontinued as no longer presents in Janssen's pipeline.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
9.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
360 mg multiple, oral
Highest studied dose
Dose: 360 mg
Route: oral
Route: multiple
Dose: 360 mg
Sources:
unhealthy, ADULT
n = 17
Health Status: unhealthy
Condition: myelodysplastic syndrome
Age Group: ADULT
Sex: M+F
Population Size: 17
Sources:
Disc. AE: ALT increased, Atrial fibrillation...
AEs leading to
discontinuation/dose reduction:
ALT increased (5.9%)
Atrial fibrillation (5.9%)
ALT increased (grade 3, 5.9%)
Sources:
AEs

AEs

AESignificanceDosePopulation
ALT increased 5.9%
Disc. AE
360 mg multiple, oral
Highest studied dose
Dose: 360 mg
Route: oral
Route: multiple
Dose: 360 mg
Sources:
unhealthy, ADULT
n = 17
Health Status: unhealthy
Condition: myelodysplastic syndrome
Age Group: ADULT
Sex: M+F
Population Size: 17
Sources:
Atrial fibrillation 5.9%
Disc. AE
360 mg multiple, oral
Highest studied dose
Dose: 360 mg
Route: oral
Route: multiple
Dose: 360 mg
Sources:
unhealthy, ADULT
n = 17
Health Status: unhealthy
Condition: myelodysplastic syndrome
Age Group: ADULT
Sex: M+F
Population Size: 17
Sources:
ALT increased grade 3, 5.9%
Disc. AE
360 mg multiple, oral
Highest studied dose
Dose: 360 mg
Route: oral
Route: multiple
Dose: 360 mg
Sources:
unhealthy, ADULT
n = 17
Health Status: unhealthy
Condition: myelodysplastic syndrome
Age Group: ADULT
Sex: M+F
Population Size: 17
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Role of the p38 mitogen-activated protein kinase pathway in the generation of arsenic trioxide-dependent cellular responses.
2006 Jul 1
Inhibition of p38alpha MAPK enhances proteasome inhibitor-induced apoptosis of myeloma cells by modulating Hsp27, Bcl-X(L), Mcl-1 and p53 levels in vitro and inhibits tumor growth in vivo.
2006 Jun
Design and synthesis of piperazine-indole p38 alpha MAP kinase inhibitors with improved pharmacokinetic profiles.
2010 Feb 1
Patents

Sample Use Guides

Myelodysplastic Syndromes: tablets should be administered orally at a dose of 30, 60, 90 or 120 mg thrice daily for 16 weeks. Multiple Myeloma: two 30-mg capsules three times daily. Rheumatoid Arthritis: 30 mg, 60 mg, 90 mg administered dailly for 30 days or 60 mg for one week followed by 120 for one week followed by 180 mg for two weeks.
Route of Administration: Oral
Bone marrow mononuclear cells (BMMNC) (1 × 10(6)) were cultured in the absence or presence of increasing concentrations of talmapimod (0, 10, 20, 50, 100, 500 nM) for 24h without or with 10 ng/mL LPS. The drug was shown to potently inhibit the secretion of TNFalpha from both basal or LPS-induced cell cultures with an IC50 of 50 nM.
Substance Class Chemical
Created
by admin
on Sat Dec 16 18:03:03 UTC 2023
Edited
by admin
on Sat Dec 16 18:03:03 UTC 2023
Record UNII
B1E00KQ6NT
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TALMAPIMOD
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
TALMAPIMOD [USAN]
Common Name English
Talmapimod [WHO-DD]
Common Name English
talmapimod [INN]
Common Name English
SCIO 469
Code English
SCIO-469
Code English
2-[6-Chloro-5-[[(2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazin-1-yl]carbonyl]-1-methyl-1H-indol-3-yl]-N,N-dimethyl-2-oxoacetamide
Systematic Name English
1H-INDOLE-3-ACETAMIDE, 6-CHLORO-5-(((2R,5S)-4-((4-FLUOROPHENYL)METHYL)-2,5-DIMETHYL-1-PIPERAZINYL)CARBONYL)-N,N,1-TRIMETHYL-.ALPHA.-OXO-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C2149
Created by admin on Sat Dec 16 18:03:03 UTC 2023 , Edited by admin on Sat Dec 16 18:03:03 UTC 2023
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 18:03:03 UTC 2023 , Edited by admin on Sat Dec 16 18:03:03 UTC 2023
Code System Code Type Description
SMS_ID
100000174942
Created by admin on Sat Dec 16 18:03:03 UTC 2023 , Edited by admin on Sat Dec 16 18:03:03 UTC 2023
PRIMARY
USAN
SS-75
Created by admin on Sat Dec 16 18:03:03 UTC 2023 , Edited by admin on Sat Dec 16 18:03:03 UTC 2023
PRIMARY
PUBCHEM
9871074
Created by admin on Sat Dec 16 18:03:03 UTC 2023 , Edited by admin on Sat Dec 16 18:03:03 UTC 2023
PRIMARY
ChEMBL
CHEMBL514201
Created by admin on Sat Dec 16 18:03:03 UTC 2023 , Edited by admin on Sat Dec 16 18:03:03 UTC 2023
PRIMARY
CAS
309913-83-5
Created by admin on Sat Dec 16 18:03:03 UTC 2023 , Edited by admin on Sat Dec 16 18:03:03 UTC 2023
PRIMARY
FDA UNII
B1E00KQ6NT
Created by admin on Sat Dec 16 18:03:03 UTC 2023 , Edited by admin on Sat Dec 16 18:03:03 UTC 2023
PRIMARY
NCI_THESAURUS
C79841
Created by admin on Sat Dec 16 18:03:03 UTC 2023 , Edited by admin on Sat Dec 16 18:03:03 UTC 2023
PRIMARY
INN
8957
Created by admin on Sat Dec 16 18:03:03 UTC 2023 , Edited by admin on Sat Dec 16 18:03:03 UTC 2023
PRIMARY
EPA CompTox
DTXSID10953119
Created by admin on Sat Dec 16 18:03:03 UTC 2023 , Edited by admin on Sat Dec 16 18:03:03 UTC 2023
PRIMARY
CHEBI
90683
Created by admin on Sat Dec 16 18:03:03 UTC 2023 , Edited by admin on Sat Dec 16 18:03:03 UTC 2023
PRIMARY
DRUG BANK
DB05412
Created by admin on Sat Dec 16 18:03:03 UTC 2023 , Edited by admin on Sat Dec 16 18:03:03 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY