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Showing posts from January, 2014

#ICanHazStructurez

I needed a pdf for a presentation I was giving this morning, I was in a hotel, which doesn't have an institutional subscription, so was stuck. On twitter, there is a hashtag #ICanHazPDF, which is quite successful, but to be clear I didn't use that route ;{o .

It got me thinking though, given the reach and immediacy of twitter, could I use it to get chemical structures - so #ICanHazStructurez was born. It worked, well in fact, and was very quick (see the image above - remember this was 6 am in the morning (in Germany at least).

So a big high five to @Lewis_Lab and @nickholway - FF and all that!

New Drug Approvals 2013 - Pt. XXIII Bazedoxifene (DUAVEE™)

wikipedia:bazedoxifene ATC code:G03XC02
On 3 October 2013, FDA approved a new drug,bazedoxifene in combination with estrogen (trade name DUAVEE™), for treatment of moderate-to-sever vasomotor symptoms (hot flashes) associated with menopause and the prevention of postmenopausal osteoporosis in women. Bazedoxifene reduces the risk of excessive growth of the uterus (endothermetrial hyperplasia) that can be caused by estrogen.

Bazedoxifene (IUPAC name: 1-{4-[2-(Azepan-1-yl)ethoxy]benzy}-2-(4-hydroxyphenyl}-3-methyl-1H-indole-5-ol) is an indole based small molecule of molecular weight of 470.6 g/mol, polar surface area of 57.9, seven rotatable bonds, four hydrogen bond acceptors and one hydrogen bond donor. The compound is lipophilic with alogP 7.22, ApKa 10.12 and logD of 5.17. The compound is also known as WAY-140424, Bazedoxifene Acetate, Bazedoxifene, SID144206564, or SID124893775.
Canonical Smiles: Cc1c(c2ccc(O)cc2)n(Cc3ccc(OCCN4CCCCCC4)cc3)c5ccc(O)cc15 Standard InchI: InChI=1S/C30H34N2O3/…

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 (CHEMBL2105689; Pubchem : 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=…

New Drug Approvals 2013 - Pt. XXI - Eslicarbazepine Acetate (AptiomTM)

Wikipedia: Eslicarbazepine Acetate

On November 8th 2013, FDA approved Eslicarbazepine Acetate (tradename: Aptiom; research codes: Sep-0002093, BIA 2-093; ChEMBL: CHEMBL87992), a prodrug indicated as adjunctive treatment of partial-onset seizures associated with epilepsy.

Epilepsy is neurological disorder characterised by abnormal neuronal activity in the brain. Partial-onset seizures, as opposed to generalised seizures, affect initially only one part of the brain and, depending on the part of the brain that is affected, these seizures will present different symptoms.

Eslicarbazepine (ChEMBL: CHEMBL315985), the bioactive ingredient of the prodrug Eslicarbazepine Acetate, exerts its anticonvulsant activity by blocking the voltage-gated sodium channel (VGSC). VGSC has 3 distinctive states: the resting state, during which the VGSC is closed but responsive to a depolarisation impulse, the open state, during which the channel is open allowing the sodium ion to enter the cell, and the inact…

ADME SARfari: A tool for predicting and comparing cross-species ADME targets

ADME studies are focused on understanding the disposition of a compound within an organism and the results of such studies play a critical role in the drug development process. ADME studies (more commonly referred to as pharmacokinetic or PK studies) are focused on 4 main areas: Absorption, Distribution, Metabolism and Excretion. More information on the PK measurement types can be found here.
Comparisons of PK data across species is a potential problem drug researchers need to deal with, as model organism studies are the primary source of such data. For example, in an animal model study, which may be carried out on a compound as it passes through the drug development pipeline, is it meaningful to compare clearance or bioavailability data from a mouse or rat to human? Clearly there are many differences (physical, metabolic, genetic,..), which make answering these types of questions difficult. Building tools which guide researchers to potential answers or provide a better und…

New Drug Approvals 2013 - Pt. XX - Simeprevir (OlysioTM)

ATC Code:J05AE14
Wikipedia:Simeprevir

On November 22th 2013, the FDA approved simeprevir (Tradename: Olysio; Research Code(s): TMC-435; TMC435350), a Hepatitis C virus NS3/NS4A protease (HCV NS3/NS4A) inhibitor, for the treatment of chronic hepatitis C virus genotype 1 infection, in combination with peginterferon alfa and ribavirin.
Chronic hepatitis C is a prolonged infection that affects the liver and is caused by a small single-stranded RNA virus, which is transmitted by blood-to-blood contact. Chronic hepatitis C is normally asymptomatic, but may lead to liver fibrosis, and thus liver failure.
Simeprevir is an inhibitor of the hepatitis C virus (HCV) serine protease NS3/NS4A (ChEMBLID:CHEMBL2095231; Uniprot ID:A3EZI9, D2K2A8; Pfam:PF02907), a viral protein complex required for the proteolytic cleavage of the HCV encoded polyprotein (UniProt:P27958) into mature forms of the NS4B, NS5A and NS5B proteins. These proteins are involved in the formation of the virus replication complex, a…