Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C27H30ClFN4O3.ClH |
| Molecular Weight | 549.464 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.C[C@H]1CN([C@H](C)CN1CC2=CC=C(F)C=C2)C(=O)C3=CC4=C(C=C3Cl)N(C)C=C4C(=O)C(=O)N(C)C
InChI
InChIKey=FOJUFGQLUOOBQP-MCJVGQIASA-N
InChI=1S/C27H30ClFN4O3.ClH/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;1H/t16-,17+;/m0./s1
| 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 |
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
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.
Originator
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
399.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21285160/ |
60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TALMAPIMOD plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
199.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21285160/ |
30 mg 1 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TALMAPIMOD plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
196.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21285160/ |
100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TALMAPIMOD plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
6 h |
3 mg/kg 1 times / day multiple, oral dose: 3 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
TALMAPIMOD plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Doses
| Dose | Population | Adverse events |
|---|---|---|
360 mg multiple, oral Highest studied dose |
unhealthy, ADULT |
Disc. AE: Atrial fibrillation, ALT increased... AEs leading to discontinuation/dose reduction: Atrial fibrillation (5.9%) Sources: ALT increased (grade 3, 5.9%) ALT increased (5.9%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| ALT increased | 5.9% Disc. AE |
360 mg multiple, oral Highest studied dose |
unhealthy, ADULT |
| Atrial fibrillation | 5.9% Disc. AE |
360 mg multiple, oral Highest studied dose |
unhealthy, ADULT |
| ALT increased | grade 3, 5.9% Disc. AE |
360 mg multiple, oral Highest studied dose |
unhealthy, ADULT |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Design and synthesis of piperazine-indole p38 alpha MAP kinase inhibitors with improved pharmacokinetic profiles. | 2010-02-01 |
|
| Role of the p38 mitogen-activated protein kinase pathway in the generation of arsenic trioxide-dependent cellular responses. | 2006-07-01 |
|
| 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. | 2006-06 |
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
Edited
Mon Mar 31 18:07:49 GMT 2025
by
admin
on
Mon Mar 31 18:07:49 GMT 2025
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| Record UNII |
K6T0L6I32X
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| Record Status |
Validated (UNII)
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| Record Version |
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NON-SPECIFIC STOICHIOMETRY | |||
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16035045
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K6T0L6I32X
Created by
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |