ChEMBL Resources

Resources:
ChEMBL
|
SureChEMBL
|
ChEMBL-NTD
|
ChEMBL-Malaria
|
The SARfaris: GPCR, Kinase, ADME
|
UniChem
|
DrugEBIlity
|
ECBD

Tuesday, 14 January 2014

New Drug Approvals 2013 - Pt. XXII - Luliconazole (Luzu ™)




ATC Code: D01AC (incomplete)
Wikipedia: Not Available
ChEMBL: CHEMBL2105689

On November 14th the FDA approved Luliconazole (trade name Luzu TM) for the treatment of skin fungal infections including ringworm. Luliconazole inhibits fungal synthesis of ergosterol, required for fungal cell membranes, by inhibiting the enzyme cytochrome P450 14-alpha-demethylase (P45014DM). 


Target(s)
Like all azole antifungals, Luliconazole binds and inhibits fungal 14-alpha-demethylase (e.g. CHEMBL1681624, Uniprot Q96W81).  P45014DM is a cytochrome P450 that catalyses the oxidative removal of the 14α-methyl group from eburicol to ergosterol. Azoles bind to the haem in P45014DM via the unprotonated N atom and occupy the active site as non-competitive inhibitors.


Luliconazole (CHEMBL2105689Pubchem : 144206495 ) is a small molecule drug with a molecular weight of 354.3 Da, an AlogP of 4.03, 2 rotatable bonds, and no of 5 violations.

Canonical SMILES : Clc1ccc([C@@H]2CS\C(=C(\C#N)/n3ccnc3)\S2)c(Cl)c1
InChi: InChI=1S/C14H9Cl2N3S2/c15-9-1-2-10(11(16)5-9)13-7-20-14(21-13)12(6-17)19-4-3-18-8-19/h1-5,8,13H,7H2/b14-12+/t13-/m0/s1


Dosage
Each gram of Luzu Cream, 1% contains 10 mg of luliconazole in a white cream base.

For treatment of Interdigital Tinea Pedis: Luzu Cream, 1% should be applied to the affected and immediate surrounding area(s) once a day for two weeks.

For treatment of Tinea Cruris and Tinea Corporis: Luzu Cream, 1% should be applied to the affected skin and immediate surrounding area(s) once a day for one week.


Drug Interactions 
The potential of luliconazole to inhibit cytochrome P-450 (CYP) enzymes 1A2, 2C9, 2C19, 2D6, and 3A4 was evaluated in vitro. Based on in vitro assessment, luliconazole at therapeutic doses, particularly when applied to patients with moderate to severe Tinea Cruris, may inhibit the activity of CYP2C19 and CYP3A4. However, no in vivo drug interaction trials have been conducted to evaluate the effect of luliconazole on other drugs that are substrates of CYP2C19 and CYP3A4. 


Pregnancy
Luliconazole is classified as pregnancy category C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

The license holder is Valeant Pharmaceuticals, the highlights of the prescribing information can be found here.

No comments: