Calanolide A is an experimental non-nucleoside reverse transcriptase inhibitor (NNRTI) first acquired from the Calophyllum lanigerum, variety austrocoriaceum, trees in the Malaysian state of Sarawak by botanist John Burley in 1987. The U.S. National Cancer Institute tested calanolide A as a possible cancer treatment, but had no effect. It was later found to have potent anti-HIV activity. On return trip to Malaysia, it was found that all of the austrocoriaceum variety tree species of Calophyllum lanigerum had been cut down most likely for fuel and building material in the swamp forest near Lundu where the first tree samples were taken; however, a few existing species were eventually located in the Singapore Botanic Garden. Since the plant source is relatively rare, a total synthesis was developed in 1996. The form in current use is formulated for oral administration and produced by Sarawak MediChem in Lemont, Illinois.
Calanolide A is unique among NNRTIs in that it may bind two distinct sites in reverse transcriptase.