Research use only. This review covers published laboratory, animal and company-reported research. JXL-069 is an experimental research compound that is not approved and has no human safety data. Nothing here is a claim that any MPC inhibitor treats hair loss in people.
What is the mitochondrial pyruvate carrier?
The mitochondrial pyruvate carrier (MPC) is a protein complex in the inner mitochondrial membrane that transports pyruvate, the end product of glycolysis, into mitochondria. Its activity was characterised in the 1970s, but the genes behind it were only identified in 2012, when two independent groups showed that the proteins now called MPC1 and MPC2 form the carrier (Bricker et al., 2012; Herzig et al., 2012).
Why block the MPC?
Pyruvate that cannot enter mitochondria is more likely to be converted into lactate in the cytoplasm. Blocking the MPC therefore shifts cell metabolism towards lactate production. In hair follicle research this matters because a 2017 mouse study linked lactate production to the activation of hair follicle stem cells (Flores et al., 2017). See hair follicle stem cells and lactate for the details.
The classic inhibitors
- Alpha-cyanocinnamates: in 1975, Andrew Halestrap described the kinetics of the mitochondrial pyruvate carrier and showed that alpha-cyanocinnamate compounds inhibit it (Halestrap, 1975). This work produced UK5099, which became the standard research tool for blocking the MPC.
- Thiazolidinediones: in 2013, Divakaruni and colleagues showed that thiazolidinediones, a class of diabetes drugs, act as acute and specific inhibitors of the MPC (Divakaruni et al., 2013).
MPC inhibitors in hair follicle research
UK5099 in mice
In the 2017 UCLA study, applying UK5099 to the skin of mice in the resting phase sped up entry into the growth phase of the hair cycle. Deleting the Mpc1 gene in hair follicle stem cells had a similar effect (Flores et al., 2017).
The JXL series, including JXL-069
To improve on UK5099, the UCLA group of Michael Jung made a large series of analogues named JXL001 to JXL088 (Liu et al., 2021). Analogues with a 3,5-bis(trifluoromethyl)benzyl group raised cellular lactate production more than UK5099. JXL069, the 7-azaindole analogue, blocked pyruvate-fuelled respiration with an IC50 of about 42.8 nM, against about 140 nM for UK5099. Analogues carrying thiazolidinedione groups did not show promising activity. More than ten analogues were tested topically in shaved mice; the paper’s text does not name JXL069 among those mouse results. Read more in What is JXL-069?.
PP405 in clinical trials
Pelage Pharmaceuticals, founded by the same UCLA researchers, is developing PP405, a topical MPC inhibitor whose structure it has not published. Pelage reports that PP405 was well tolerated with no detectable drug in the blood, and a Phase 2/3 trial (AWAKEN) was registered in 2026. Efficacy figures so far are company-reported and not peer-reviewed. See PP405 explained and JXL-069 vs PP405.
Open questions
- Selectivity: how specifically each compound hits the MPC rather than other targets.
- Skin delivery: how much of a topical compound reaches the follicle stem cells.
- Systemic exposure: MPC is present in many tissues, so whether a compound stays local matters for safety.
- Translation: most of the follicle evidence is from mice, and JXL-069 has no human data at all.
- Long-term effects of blocking the MPC in skin have not been reported.
For laboratory research on MPC inhibition: JXL-069 raw powder and JXL-069 (PP405) 0.05% w/v 30mL, each with a third-party COA, for research use only.
References
- Bricker DK, Taylor EB, Schell JC, et al. A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science. 2012;337(6090):96-100. doi:10.1126/science.1218099
- Herzig S, Raemy E, Montessuit S, et al. Identification and functional expression of the mitochondrial pyruvate carrier. Science. 2012;337(6090):93-96. doi:10.1126/science.1218530
- Halestrap AP. The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem J. 1975;148(1):85-96. doi:10.1042/bj1480085
- Divakaruni AS, Wiley SE, Rogers GW, et al. Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier. Proc Natl Acad Sci USA. 2013;110(14):5422-5427. doi:10.1073/pnas.1303360110
- Flores A, Schell J, Krall AS, et al. Lactate dehydrogenase activity drives hair follicle stem cell activation. Nat Cell Biol. 2017;19(9):1017-1026. doi:10.1038/ncb3575
- Liu X, Flores AA, Situ L, et al. Development of Novel Mitochondrial Pyruvate Carrier Inhibitors to Treat Hair Loss. J Med Chem. 2021;64(4):2046-2063. doi:10.1021/acs.jmedchem.0c01570
- ClinicalTrials.gov. NCT07819435: Phase 2/3 Efficacy and Safety of PP405 in Adult Males (AWAKEN). clinicaltrials.gov
