Akt Inhibitor

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.

PI3K-IN-29 is a potent PI3K inhibitor. PI3K-IN-29 displays good inhibition potencies against U87MG, HeLa and HL60 cells with IC₅₀ values of 0.264, 2.04 and 1.14 µM, respectively. PI3K-IN-29 inhibits PI3K/Akt pathway by inhibiting phosphorylation of Akt that is catalyzed by PI3K.

PROTAC PI3K/110β degrader-2 is a VHL-recruiting PI3K/110β PROTAC degrader, with DC₅₀ values of 1.258 μM and 2.185 μM in MCF-7/ADM and A549/DDP cells, respectively. PROTAC PI3K/110β degrader-2 induces proteasomal degradation of PI3K/110β, inhibits phosphorylation of AKT and expression of Bcl-2, while suppressing the activity and expression of P-gp. It also induces endoplasmic reticulum stress and mitochondrial apoptosis via the PERK/CHOP pathway. PROTAC PI3K/110β degrader-2 exerts anti-tumor activity against multidrug-resistant cancer cells both in vitro and in vivo, and produces a synergistic effect when combined with Doxorubicin (HY-15142A) or Cisplatin (HY-17394), making it applicable for the research of multidrug-resistant cancers.

KU004 is a potent dual EGFR/HER2 inhibitor with anticancer effects. KU004 inhibits the proliferation of human breast cancer SKBR3 cells by inducing G1 phase arrest. KU004 blocks the activation of HER2, EGFR and downstream Akt and Erk pathways and induces cell Apoptosis mainly via the extrinsic pathway. KU004 is a quinazoline derivative.

VVD-844 is an orally active covalent inhibitor of PI3Kα, which inhibits Pl3Kα/p110α interaction with an IC₅₀ of 4 nM. VVD-844 covalently binds to Cys²⁴² in the RAS binding domain of p110α, blocking RAS-p110α interaction and inhibiting PI3Kα activity. VVD-844 inhibits PI3Kα signaling activation in HER2-overexpressing cells via a RAS-independent mechanism. VVD-844 suppresses tumor growth in mouse. VVD-844 can be used for the research of cancers.

FLC-8 is an orally active FLT3 inhibitor with IC₅₀ values of 10.2 nM, 11.6 nM and 24.10 nM against human FLT3-WT, FLT3-G697R and FLT3-N676D, respectively. FLC-8 inhibits FLT3 autophosphorylation and downstream STAT5, AKT and ERK signaling pathways, and induces apoptosis in acute myeloid leukemia (AML) cells. FLC-8 exhibits potent antitumor activity in the MV4-11 xenograft model. FLC-8 can be used for the research of acute myeloid leukemia.

(Z)-Guggulsterone (Standard) is the analytical standard of (Z)-Guggulsterone. This product is intended for research and analytical applications. (Z)-Guggulsterone, a constituent of Indian Ayurvedic medicinal plant Commiphora mukul, inhibits the growth of human prostate cancer cells by causing apoptosis. (Z)-Guggulsterone inhibits angiogenesis by suppressing the VEGF–VEGF-R2–Akt signaling axis. (Z)-Guggulsterone is also a potent FXR antagonist. (Z)-Guggulsterone reduces ACE2 expression and SARS-CoV-2 infection.

Trimebutine-d₅ fumarate is deuterium labeled Trimebutine fumarate. Trimebutine fumarate is a multi-target inhibitor and opioid receptor agonist with antimuscarinic activity. Trimebutine fumarate inhibits L-type Ca²⁺ channels and large-conductance calcium-activated potassium channels (BK_Ca channels), thereby inhibiting extracellular calcium influx and potassium ion efflux. Trimebutine fumarate also targets Toll-like receptors, inhibits Toll-like receptor 2/4/7/8/9 signals, and inhibits LPS-induced IRAK1 activation, as well as ERK1/2, JNK and NF-κB activation, thereby exerting anti-inflammatory effects. Trimebutine fumarate also induces tumor cell apoptosis by inhibiting the AKT/ERK pathway. Trimebutine fumarate also inhibits excessive contraction of smooth muscle and can be used in the study of gastrointestinal disorders such as irritable bowel syndrome (IBS).

2-Chlorophenoxazine is a Akt inhibitor with an IC₅₀ value of 2-5 μM for in vitro. 2-Chlorophenoxazine can induce apoptosis. 2-Chlorophenoxazine can be used for cancer diseases research.

Fusaric acid (Standard) is the analytical standard of Fusaric acid (HY-128483). This product is intended for research and analytical applications. Fusaric acid is an orally active multi-pathway inhibitor with the activity of inducing oxidative stress and apoptosis. Fusaric acid can chelate divalent metal cations, damage mitochondrial membrane structure, and activate apoptosis-related proteases such as Caspase-3/7, -8, and -9. Fusaric acid also regulates Bax/Bcl-2 protein, inhibits fibrosis-related signaling pathways such as NF-κB, TGF-β₁/SMADs, and PI3K/AKT/mTOR, and reduces collagen deposition. Fusaric acid is also a dopamine β-hydroxylase inhibitor, which reduces endogenous levels of norepinephrine and epinephrine in the brain, heart, spleen, and adrenal glands. Fusaric acid can play a role in myocardial fibrosis and improve cardiac hypertrophy in heart disease, and can also be used in the study of esophageal cancer and liver cancer.

Tizanidine-d₄ hydrochloride is deuterium labeled Tizanidine hydrochloride (HY-B0194A). Tizanidine hydrochloride, a skeletal muscle relaxant, is an orally effective central α₂-adrenoceptor agonist (IC₅₀ = 6.9 nmol). Tizanidine hydrochloride primarily exerts muscle relaxation effects by inhibiting the release of excitatory amino acids (glutamate and aspartate) from the presynaptic terminals of spinal cord interneurons. Tizanidine hydrochloride has anti-injury activity and can inhibit gastrointestinal (GI) transport. Tizanidine hydrochloride can inhibit the proliferation, migration, and invasion of lung cancer cells and induce cell apoptosis by upregulating Nischarin and inhibiting the AKT and Wnt3a/β-catenin signaling pathways. Tizanidine hydrochloride can be used to treat spasticity caused by diseases such as multiple sclerosis (MS), stroke, and spinal cord injury (SCI).

EGFR-IN-173 is an orally active, pan-mutant EGFR tyrosine kinase inhibitor that targets EGFR 19del, L858R/T790M and C797S triple-mutations, potently inhibiting EGFR^{19del/T790M/C797S} with an IC₅₀ of 1.19 nM while showing over 100-fold selectivity for mutant over wild-type EGFR (IC₅₀ = 19.362 μM against WT). EGFR-IN-173 significantly inhibits cell migration, induces apoptosis in non-small cell lung cancer (NSCLC) cells. EGFR-IN-173 inhibits EGFR phosphorylation and suppresses the downstream pathways (MAPK/ERK, AKT, STAT3). EGFR-IN-173 exhibits antitumor efficacy in NSCLC and Ba/F3 xenograft models. EGFR-IN-173 can be used for NSCLC research.

YN14 mixture of diastereomers is a diastereomer mixture of YN14 (HY-155356). YN14 is a KRAS^G12C PROTAC degrader that recruits E3 ubiquitin ligase to induce the polyubiquitination and proteasomal degradation of KRAS^G12C. YN14 induces tumor cell apoptosis, cell cycle arrest, and cell migration inhibition. YN14 exhibits in vivo antitumor proliferative activity in tumor cell xenograft nude mice. YN14 can be used in cancer-related research.

PROTAC FLT3/CHK1 Degrader-1 is a PROTAC FLT3/CHK1 degrader, with DC₅₀ values of 5.88 nM (FLT3) and 4.17 nM (CHK1), respectively. PROTAC FLT3/CHK1 Degrader-1 can inhibit the phosphorylation of FLT3 downstream signaling effectors STAT5 (Tyr694), AKT (Ser473), and ERK (Tyr204), downregulate the protein level of c-Myc and maintain the expression of p53 protein. PROTAC FLT3/CHK1 Degrader-1 induces Apoptosis in cells. PROTAC FLT3/CHK1 Degrader-1 shows significant anti-tumor efficacy in mice bearing MV-4-11 subcutaneous xenografts. PROTAC FLT3/CHK1 Degrader-1 can be used for the study of acute myeloid leukemia (AML).

PP2A Cancerous-IN-1 is a strong and potent CIP2A (Cancerous inhibitor of PP2A) and p-Akt inhibitor. PP2A Cancerous-IN-1 shows the most potent antiproliferative activities. PP2A Cancerous-IN-1 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

PROTAC SHP2 degrader-1 is a potent SHP2 PROTAC degrader with a DC₅₀ of 7.406 μM. PROTAC SHP2 degrader-1 recruits DCAF16 E3 ligase to induce ubiquitination and proteasomal degradation of SHP2, thereby inhibiting the RAS/MAPK and PI3K/AKT/mTOR signaling pathways while simultaneously inducing IFN-γ/JAK/STAT1, apoptosis, and cell cycle arrest. PROTAC SHP2 degrader-1 can be used for cancer research.

AKT-IN-14 (Example 2) free baseis a potent AKTinhibitor with the IC₅₀ values of <0.01 nM, 1.06 nM and 0.66 nM for AKT1, AKT2, AKT3, respectively. AKT-IN-14 free basecan be used in cancer research.

AKTide-2T is an excellent in vitro substrate for AKT and shows competitive inhibition of histone H2B phosphorylation with a K_i of 12 nM. AKTide-2T mimics the optimal phosphorylation sequence of Akt and is an inhibitory peptide with the wildtype AKTide lacking Thr in the S22 position.

PI3K/AKT-IN-6 is an orally effective PI3K/AKT signaling pathway inhibitor and anti-inflammatory agent. PI3K/AKT-IN-6 inhibits the production of pro-inflammatory cytokines TNF-α and IL-6, and downregulates the expression of inflammatory mediators COX-2 and iNOS. PI3K/AKT-IN-6 improves related symptoms in colitis mice. PI3K/AKT-IN-6 can be used for the research of inflammatory diseases such as colitis.

NGI‑189 is a selective OST‑A inhibitor. NGI‑189 inhibits the STT3A catalytic subunit of the OST complex and reduces N‑glycosylation of target glycoproteins. NGI‑189 blocks oncogenic and bypass signaling, reduces phosphorylation of EGFR, AKT, p70S6K and S6RP, and induces cell cycle arrest and apoptosis. NGI‑189 markedly suppresses tumor growth and induces tumor regression in non‑small cell lung cancer (NSCLC) xenograft models. NGI‑189 can be used for the research of EGFR‑mutant non‑small cell lung cancer.