Wednesday, October 21, 2015

Drugs in Clinical Pipeline: Tafenoquine

Tafenoquine [N-[2,6-Dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl]pentane-1,4-diamine] is a Primaquine analogue. It is a member of the 8-aminoquinoline group of drugs that includes Primaquine and seldom used drug, Pamaquine. Tafenoquine is being manufactured by GlaxoSmithKline, where the drug is being investigated as a potential treatment for malaria, as well as for malaria prevention [1]. Tafenoquine is a long-acting analogue of primaquine. For non-immune travelers travelling to endemic areas for few weeks, Tafenoquine, has the potential to be the drug of choice. Besides, on leaving the endemic region, Tafenoquine need not be continued as it has an extended half-life and potential transmission blocking properties. Hence there are minimum chances of treatment failure due to non-compliance.

The distinct advantages of Tafenoquine are:

1. Proven activity against blood and liver stage parasites.

2. It has a long half life.

3. Better compliance.

4. Potential of being the drug of choice for travelers to endemic areas for short periods.

5. The drug can be stopped immediately upon leaving endemic area.

6. Chemoprophylactic properties against both P. falciparum and P. vivax.

7. The drug has a potential for radical cure of P. vivax.

8. Moreover, it has additional gametocidal and sporontocidal activity.

In December 2013, US Food and Drug Administration (US-FDA) granted "breakthrough therapy" designation for the investigational antimalarial drug Tafenoquine. Co-developers GlaxoSmithKline and the Medicines for Malaria Venture, have credited this to the ability of Tafenoquine to target Plasmodium vivax malaria, including a form that lies dormant in the liver and causes relapse of infection within weeks to months of the initial mosquito bite. An estimated 70 million to 390 million clinical cases of uncomplicated malaria caused by P. vivax occur annually with significant public health and economic consequences in South and East Asia, Latin America, and the horn of Africa. The drug, administered in a single dose, would be indicated for both malaria treatment and relapse prevention.

Common Name: Tafenoquine
Synonyms: SB-252263; SB252263; SB 252263; WR-238605; WR238605; WR 238605
IUPAC Name: N-[2,6-Dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl]pentane-1,4-diamine
CAS Number: 106635-80-7
Mechanism of Action: 
Indication: Anti-Malarial
Development Stage: Phase III
Company: GlaxoSmithKline/Medicines for Malaria Venture

1. Prashar, L.; et. al. Tafenoquine: A New 8-Aminoquinoline. Medical Journal of Zambia 2009, 36(4), 187-190.