PP405

PP405 is the development code of a synthetic small molecule that PubChem's synonym list ties to an inhibitor of the mitochondrial pyruvate carrier (MPC), the inner-membrane transporter that moves pyruvate into mitochondria. It is not a peptide. PubChem lists PP405 as a synonym on its record for JXL069, a UK-5099 analog made by UCLA chemists (Liu et al., 2021). The JXL series grew out of UCLA mouse work in which hair follicle stem cells needed lactate dehydrogenase activity to activate, and deleting or blocking the carrier accelerated the hair cycle (Flores et al., 2017).

The senior authors of that work, Heather Christofk and William Lowry, disclosed in 2019 that they are founders of Pelage Pharmaceuticals (Flores et al., 2019), and a 2025 review names PP405 as that company's lead compound (Kim et al., 2025).

Those come from PubChem CID 137374808. On that record, PP405, PP-405 and suvomipic come from a single depositor entry, the IUPHAR/BPS Guide to Pharmacology (added 18 September 2026), which lists them alongside JXL069; the other depositors that name the compound list only JXL069 or JXL-069. The formula matches the one reported for JXL069 in its journal characterization data (Liu et al., 2021).

The work behind PP405 falls into five preclinical areas. The only paper whose PubMed abstract names PP405 is a 2026 review listing it among "metabolic and follicular activators" (Agrawal et al., 2026). None of the studies below used Disguised Alpha's product.

The target: the mitochondrial pyruvate carrier

In 2012 two groups identified the carrier as a complex of two membrane proteins, MPC1 and MPC2. Yeast lacking them showed severe defects in mitochondrial pyruvate uptake, and mouse MPC1 and MPC2 expressed together in Lactococcus lactis bacteria transported pyruvate (Herzig et al., 2012).

Silencing either protein in mammalian cells impaired pyruvate oxidation, and a point mutation in MPC1 gave resistance to a known carrier inhibitor (Bricker et al., 2012). Work on purified human MPC showed that its functional unit is a hetero-dimer and that potent inhibitors share three closely spaced hydrogen bond acceptors followed by an aromatic ring (Tavoulari et al., 2022). Models: yeast, bacteria, mammalian cells and purified protein.

Lactate dehydrogenase and hair follicle stem cells in mice

Hair follicle stem cells rest during telogen and activate when a new hair cycle (anagen) begins. Flores et al. found that these cells are glycolytic and make more lactate than other epidermal cells. Deleting lactate dehydrogenase A (Ldha) in them blocked their activation; with an Lgr5-driven Cre, at least 20 littermate pairs failed to enter anagen.

Deleting Mpc1 instead raised Ldh activity in sorted stem cells and accelerated the hair cycle (12 littermate pairs with each of two Cre lines), and long-term deletion caused no abnormal follicles or stem-cell exhaustion on histology and Sox9 staining. UK-5099 applied to the skin of mice in telogen accelerated the hair cycle in as few as 6 to 9 days (at least 6 pairs), raised Ldh activity and lactate in the stem cells, and caused minor hyperproliferation of the interfollicular epidermis (Flores et al., 2017). Model: mice.

From UK-5099 to JXL069

UK-5099 was characterized in 1975, halving pyruvate-dependent oxygen uptake by rat heart mitochondria at 50 nM (Halestrap, 1975). The UCLA chemists varied four positions of UK-5099 (their JXL001) and screened analogs for lactate output in MCF10A human breast epithelial cells at 10 µM. A 3,5-bis(trifluoromethyl)benzyl group on the ring nitrogen (JXL020) beat the parent, and the 7-azaindole version, JXL069, outperformed its 4- and 6-azaindole counterparts and JXL020 in that screen. Against pyruvate-driven respiration in permeabilized MCF10A cells, IC50 values were about 140 nM for JXL001, 16.6 nM for JXL020 and 42.8 nM for JXL069.

In shaved telogen mice, analogs applied every other day in a lotion brought pigmentation and visible hair, signs of anagen entry, by about day 8; vehicle-treated mice showed neither at day 12. The authors say this assay was not quantitative enough to rank compounds, and JXL069 is not among UK-5099 and the 12 analogs in the mouse figure. Four authors share a patent application that includes the molecules (Liu et al., 2021). Models: MCF10A cells and mice.

MPC inhibition in mouse models of refractory hair cycling

Flores and Lowry, now also listing Pelage Pharmaceuticals, Inc. as an affiliation, then built mouse models in which hair cycling is refractory because of age, repeated chemotherapy or stress. Inhibiting pyruvate transport into mitochondria still accelerated the hair cycle in these models, and histologically normal follicles formed within 30 to 40 days; the abstract does not name the inhibitor (Flores et al., 2021).

An independent Shanghai group made 32 α-cyano-4-hydroxycinnamate derivatives; its lead, SIPI11594, outperformed UK-5099 on cellular lactate and anagen entry in depilated C57BL/6J mice, a depilation model rather than a refractory one (Zhang et al., 2026). Models: mice and cultured cells.

Beyond the follicle: intestinal stem cells and skin tumors

MPC loss affects other stem cells too. In mice, deleting Mpc1 in Lgr5-positive intestinal stem cells, or adding UK-5099 to intestinal organoids, increased proliferation and expanded the stem cell compartment (Schell et al., 2017).

Because hair follicle stem cells can give rise to squamous cell carcinoma in mice, the UCLA group also tested skin tumor models: deleting Ldha did not change tumor number, timing or volume, and deleting Mpc1 roughly doubled tumor Ldh activity without changing the timing or degree of tumorigenesis, including in a milder Kras-only model (Flores et al., 2019). Models: mice and intestinal organoids.