Losmapimod is a promising new agent against cardiovascular diseases. This compound works by inhibiting p38 MAP kinases, which play an important role in the development of atherosclerosis and heart failure caused by ischemic conditions. Losmapimod did not cause an improvement in exercise tolerance or lung function, despite being well-tolerated in this COPD population.The p38 MAPK inhibitor losmapimod (GW856553) attenuates the pro-inflammatory response in humans by reducing PIC production.
|Animal models||Spontaneously hypertensive stroke-prone rats|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
A low-frequency variant in MAPK14 provides mechanistic evidence of a link with myeloperoxidase: a prognostic cardiovascular risk marker.
Waterworth DM, et al. J Am Heart Assoc. 2014 Aug 27;3(4). PMID: 25164947.
Losmapimod, a novel p38 mitogen-activated protein kinase inhibitor, in non-ST-segment elevation myocardial infarction: a randomised phase 2 trial.
Newby LK, et al. Lancet. 2014 Sep 27;384(9949):1187-95. PMID: 24930728.
Evaluation of antidepressant properties of the p38 MAP kinase inhibitor losmapimod (GW856553) in Major Depressive Disorder: Results from two randomised, placebo-controlled, double-blind, multicentre studies using a Bayesian approach.
Inamdar A, et al. J Psychopharmacol. 2014 Apr 2;28(6):570-581. PMID: 24699061.
Efficacy and safety of the p38 MAPK inhibitor losmapimod for patients with chronic obstructive pulmonary disease: a randomised, double-blind, placebo-controlled trial.
Watz H, et al. Lancet Respir Med. 2014 Jan;2(1):63-72. PMID: 24461903.
Losmapimod: a novel drug against cardiovascular diseases?
Dewenter M, et al. Dtsch Med Wochenschr. 2013 Jan;138(1-2):39-42. PMID: 23250695.
Safety, tolerability, pharmacokinetics and pharmacodynamics of losmapimod following a single intravenous or oral dose in healthy volunteers.
Barbour AM, et al. Br J Clin Pharmacol. 2013 Jul;76(1):99-106. PMID: 23215699.
|Related p38 MAPK Products|
Pexmetinib (ARRY-614) is a potent, orally bioavailable, dual p38 MAPK/Tie-2 inhibitor with IC50 of 4 nM/18 nM in a HEK-293 cell line. Phase 1.
VX-745 is a potent and selective inhibitor of p38α with IC50 of 10 nM, 22-fold greater selectivity versus p38β and no inhibition to p38γ.
TAK-715 is a p38 MAPK inhibitor for p38α with IC50 of 7.1 nM, 28-fold more selective for p38α over p38β, no inhibition to p38γ/δ, JNK1, ERK1, IKKβ, MEKK1 or TAK1.
Skepinone-L is a selective p38α-MAPK inhibitor with IC50 of 5 nM.
PD 169316 is a potent, cell-permeable and selective p38 MAP kinase inhibitor with IC50 = 89 nM.
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