PDK-1 Inhibitor

(R)-PS210, the R enantiomer of PS210 (compound 4h-eutomer), is a substrate-selective allosteric activator of PDK1 with an AC₅₀ value of 1.8 μM. (R)-PS210 targets to the PIF-binding pocket of?PDK1. PIF: The protein kinase C-related kinase 2 (PRK2)-interacting fragment.

PDK1-IN-1 (Compound 2-11) is a PDK1 inhibitor. PDK1-IN-1 is also useful as inhibitor of other kinases such as FGFR3, NTRK3, RP-S6K and WEE1. PDK1-IN-1 selectively inhibits microtubule affinity regulating kinase (MARK). PDK1-IN-1 can be used for researches of myeloproliferative disorders, cancer and Alzheimer's disease.

PKM2 activator 6 (Compound Z10) is a PKM2 activator and PDK1 inhibitor (K_D: 121 and 19.6 μM respectively). PKM2 activator 6 induces colorectal cell apoptosis, and inhibits cell proliferation and migration . PKM2 activator 6 inhibits glycolysis. PKM2 activator 6 inhibits proliferation of DLD-1, HCT-8, HT-29, MCF-10A cells (IC₅₀: 10.04, 2.16, 3.57, 66.39 μM).

PDK1-IN-4 (Compound R-29) is a PDK1 inhibitor. PDK1-IN-4 can be used for research of lung cancer.

PDK1-IN-3 (Compound C) is a PDK1 inhibitor, with an IC₅₀ of 34 nM.

LDHA/PDKs-IN-1 (compound 20e) is a potent and dual inhibitor of PDKs and LDHA with IC₅₀s of 0.8 and 0.15 μM, respectively. LDHA/PDKs-IN-1 reduces A549 cell proliferation with an EC₅₀ of 13.2 μM and decreases the lactate formation, and increases oxygen consumption. LDHA/PDKs-IN-1 has the potential for the research of cancer diseases.

OSU-02067 is a selective 3-phosphoinositide-dependent protein kinase-1 (PDK-1) inhibitor (IC₅₀=9 μM). OSU-02067 is promising for research of solid tumors (e.g., prostate, breast, colorectal cancers).

Solenopsin ((-)-Solenopsin A) is an ATP-competitive and selective Akt-1 inhibitor with an IC₅₀ of 5-10 μM, and also acts as an RSK1 inhibitor. Solenopsin inhibits the activities of PDK1 in lipid rafts, downregulates PI3K, blocks PI3K-dependent generation of 3-phosphoinositides, and suppresses the phosphorylation of FOXO1a. Solenopsin induces Mitophagy and ROS production, reduces mitochondrial oxygen consumption, and exhibits antiproliferative and antiangiogenic activities. Solenopsin can be used in research related to hyperproliferative skin diseases and malignant diseases.

WH23 is a dehydrogenase/reductase SDR family member 11 (DHRS11) inhibitor with IC₅₀ values of 0.037 μM. WH23 binds to DHRS11, forming a hydrogen bond with the enzyme’s His210 residue. WH23 suppresses androgen receptor mRNA and protein expression, reduces c-Myc expression, and inhibits cancer cell proliferation. WH23 inhibits PI3K/AKT signaling by reducing phosphorylation of PDK1, AKT, mTOR, and ERK. WH23 enhances Capivasertib (HY-15431)-induced cytotoxicity and apoptosis. WH23 can be used for the research of luminal androgen receptor-positive triple-negative breast cancer.

Bisdemethoxycurcumin is an orally effective curcuminoid. Bisdemethoxycurcumin downregulates pro-inflammatory cytokines in macrophages by inhibiting the phosphorylation of PI3K/Akt and p38 MAPK. Bisdemethoxycurcumin relieves autophagy inhibition and promotes lipophagy to clear vascular smooth muscle foam cells by inhibiting the PDK1/Akt/mTOR pathway. Bisdemethoxycurcumin activates the cAMP/Epac/AMPKα axis and the NRF2/HO-1 antioxidant axis, thereby indirectly inhibiting the phosphorylation of NF-κB p65 and pro-inflammatory outputs such as IL-1β/IL-6/TNF-α, so as to alleviate pulmonary oxidative stress, inflammatory infiltration and pulmonary edema. Bisdemethoxycurcumin blocks NLRP3-mediated pyroptosis and protects cartilage extracellular matrix degradation by activating NRF2/HO-1. Bisdemethoxycurcumin also exerts a synergistic effect with potassium iodide against Candida.

PDK1-IN-5 is a selective PDK1 inhibitor. PDK1-IN-5 activaties PDH by diminishing phosphorylation level via PDK1 inhibition. PDK1-IN-5 effectively reverses the Warburg effect and shifts cellular energy metabolism from glycolysis toward oxidative phosphorylation by increased acetyl-CoA, reduced lactate, elevated mitochondrial ROS, and subsequent induction of apoptosis. PDK1-IN-5 robustly inhibits tumor growth in vivo without inducing systemic toxicity. PDK1-IN-5 can be used for lung adenocarcinoma, human non-small cell lung adenocarcinoma and gastric colorectal.

MG-Lin1 is a Lin28/Lin28A molecular glue degrader with a DC₅₀ of approximately 0.7 μM. It induces Lin28 degradation via the ubiquitin-proteasome pathway by forming a ternary complex, thereby upregulating the levels of let-7 miRNA and reducing the expression of its downstream oncogenic targets KRAS and PDK1, and inhibiting cancer cell migration. MG-Lin1 can be used in studies of ovarian cancer and choriocarcinoma.

X-370 is a PI3Kδ inhibitor (IC₅₀ = 7 nM). X-370 inhibits the survival of leukemia cells, inducing G1 arrest and apoptosis. X-370 blocks PDK1 binding and phosphorylation of MEK1/2, eliminating Akt and Erk1/2 signaling. X-370 can be used in research on B-cell acute lymphoblastic leukemia (B-ALL).

LDHA/PDKs-IN-2 (compound 20k) is a potent and dual inhibitor of PDKs and LDHA with IC₅₀s of 1.6 and 0.7 μM, respectively. LDHA/PDKs-IN-2 reduces A549 cell proliferation with an EC₅₀ of 15.7 μM and decreases the lactate formation, and increases oxygen consumption. LDHA/PDKs-IN-2 has the potential for the research of cancer diseases.

PKM2/PDK1-IN-1, one of shikonin thioether derivatives, is a dual inhibitor of PKM2/PDK1. PKM2/PDK1-IN-1 inhibits the proliferation of NSCLC cells, and induces apoptosis. PKM2/PDK1-IN-1 induces intercellular ROS production, and regulates the apoptotic proteins, to involves in mitochondrial and death receptor pathway.

BX-912 (Standard) is the analytical standard of BX-912 (HY-11005). This product is intended for research and analytical applications. BX-912 is a direct, selective, and ATP-competitive PDK1 inhibitor (IC₅₀=26 nM). BX-912 blocks PDK1/Akt signaling in tumor cells and inhibits the anchorage-dependent growth of a variety of tumor cell lines in culture or induces apoptosis.

OSU-03012 (Standard) is the analytical standard of OSU-03012 (HY-10547). This product is intended for research and analytical applications. OSU-03012 (AR-12; PDK1 inhibitor AR-12) is a blood-brain permeable PDK-1 inhibitor with an IC₅₀ of 5 μM.

PF-5177624 is a specific and potent inhibitor of PDK1, a key enzyme in the PI3K/AKT signaling pathway that is frequently dysregulated in breast cancer. PDK1 phosphorylates AKT at T308 and other substrates, activating downstream signaling pathways that are important for tumor progression. PF-5177624 blocks IGF-1-stimulated PDK1 activity and downstream AKT and p70S6K phosphorylation, reducing cell proliferation and transformation in breast cancer cells.

mIDH1-IN-2 is a brain-penetrant isocitrate dehydrogenase 1 (IDH1) inhibitor. mIDH1-IN-2 shows subnanomolar potency against IDH1 R132H and R132C (IC₅₀ = 80.0 and 58.0 nM) and minimal activity against wt-IDH1/2. mIDH1-IN-2 also inhibits PDK1 (IC₅₀ = 0.61 μM) and reduces PDH phosphorylation dose-dependently. mIDH1-IN-2 can inhibit cells proliferation, induces S phase arrest and promotes apoptosis. mIDH1-IN-2 can be used for the research of cancer, such as glioma.

BX795 (Standard) is the analytical standard of BX795 (HY-10514). This product is intended for research and analytical applications. BX795 is a potent and selective inhibitor of PDK1, with an IC₅₀ of 6 nM. BX795 is also a potent and relatively specific inhibitor of TBK1 and IKKε, with an IC₅₀ of 6 and 41 nM, respectively. BX795 blocks phosphorylation of S6K1, Akt, PKCδ, and GSK3β, and has lower selectivity over PKA, PKC, c-Kit, GSK3β etc. BX795 modulates autophagy.