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
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
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
Doses
| Dose | Population | Adverse events |
|---|---|---|
360 mg multiple, oral Highest studied dose |
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%) Sources: Atrial fibrillation (5.9%) ALT increased (grade 3, 5.9%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| ALT increased | 5.9% Disc. AE |
360 mg multiple, oral Highest studied dose |
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 |
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 |
unhealthy, ADULT n = 17 Health Status: unhealthy Condition: myelodysplastic syndrome Age Group: ADULT Sex: M+F Population Size: 17 Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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 |
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.
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C2149
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C129825
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C79841
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DB05412
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)
