Since I first read it here [1] I have been following the authorization for marketing procedure of medicinal products based on bempedoic acid (Nilemdo) and bempedoic acid and ezetimibe (Nustendi). Over here in EU they got some traction lately:
"On 30 January 2020, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Nilemdo, intended for the treatment of adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia." [2]
Apart from being claimed as more liver-friendly, compared to statines when used alone, they can complement the latter for further reduction of total cholesterol and LDL-C. The way they achieve this is by interfering with ATP Citrate Lyase (ACLY). The interesting part here is that by targeting ACLY they may be of further interest to us.
a) "Studies have shown a role for ACLY in tumorigenesis whereby increased levels of the enzyme leads to increased metabolic activity via activation of Akt signaling. Increasing lines of evidence suggest that enzymes involved in lipid biogenesis play a significant role in cancer cell proliferation and progression." (2015) [3]
b) "ACLY is a key enzyme in cancer metabolism. ACLY is involved in glucose and lipid metabolism. Many ACLY inhibitors were developed as anti-cancer agents." (2018) [4]
c) "Targeting ACLY sensitizes castration-resistant prostate cancer cells to AR antagonism by impinging on an ACLY-AMPK-AR feedback mechanism...
The ACLY-AMPK-AR network can be exploited to sensitize CRPC cells to AR antagonism, suggesting novel therapeutic opportunities for prostate cancer." [5]
d) "Scientists decipher 3D structure of a promising molecular target for cancer treatment... The team has successfully determined the 3D structure of human ATP-citrate lyase (ACLY) -which plays a key role in cancer cell proliferation and other cellular processes - for the first time." (2019) [6]
So far, so good, but until the bembedoic acid pils become available at a pharmacy near you, is it possible that:
"dietary supplementation of hydroxycitrate (HCA), a competitive inhibitor of the extramitochondrial enzyme ATP-citrate-lyase, which inhibits lipogenesis" [7]
can be used as a substitute?
Just wondering and waiting for the usual "suspects" to chime in.
[1] healthunlocked.com/advanced...
[2] ema.europa.eu/en/documents/...
[3] eurekaselect.com/127128/art...
[4] sciencedirect.com/science/a...
[5] omictools.com/0cb3f41a97805...
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