SphK2 Inhibitor

SKI-II is an orally active dual-target inhibitor of SphK1/2 and DES1, with K_i values of 16 µM and 0.3 µM against SphK1 and DES1, respectively. SKI-II activates the PERK-Nrf2 antioxidant pathway by stabilizing Nrf2, and synergizes with Temozolomide (HY-17364) to induce oxidative/endoplasmic reticulum stress and cancer cell death under hypoxic conditions. In vivo, SKI-II inhibits SphK activity, promotes ceramide accumulation and apoptosis, and synergizes with Cisplatin (HY-17394) to reverse drug resistance via the ras/MAPK pathway. SKI-II reduces measles virus replication by inhibiting mTORC1 activity. SKI-II binds to VCP to induce M1 polarization, enhances host tolerance to Staphylococcus aureus infection, and exerts radioprotective effects through Nrf2 activation and accelerated DNA repair. SKI-II can be used in research related to glioblastoma, acute myeloid leukemia, gastric cancer, measles virus infection, Staphylococcus aureus infection, and acute radiation syndrome.

K145 hydrochloride is a selective, substrate-competitive and orally active SphK2 inhibitor with an IC₅₀ of 4.3 μM and a K_i of 6.4 μM. K145 hydrochloride is inactive against SphK1 and other protein kinases. K145 hydrochloride induces cell apoptosis and has potently antitumor activity.

SKI-178 is a potent sphingosine kinase-1 (SphK1) and SphK2 inhibitor. SKI-178 is cytotoxic at IC₅₀ concentrations ranging from 1.8 to 0.1 μM in both agent sensitive and multi-agent resistant cancer cell lines (i.e., MTR3, NCI-ADR and HL60/VCR cells). SKI-178 induces apoptosis in a CDK1-dependent manner in human acute myeloid leukemia cell lines.

Amgen-23 (compound 23) is a potent sphingosine kinases (SPHK) inhibitor with IC₅₀ values of 20 nM and 1.6 μM for SPHK1 and SPHK2, respectively. Amgen-23 can be used for researching anticancer.

SLM6031434 hydrochloride is the hydrochloride salt form of SLM6031434 (HY-120268). SLM6031434 is a highly selective sphingosine kinase 2 (SphK2) inhibitor with an IC₅₀ value of 0.4 μM for SphK2. SLM6031434 exerts anti-fibrotic effects by increasing sphingosine accumulation and Smad7 expression. SLM6031434 demonstrates effective anti-fibrotic efficacy in a unilateral ureteral obstruction (UUO)-induced tubulointerstitial fibrosis mouse model. SLM6031434 can be used for the study of proteinuric kidney diseases or chronic kidney disease (CKD).

RB-042 is a SK1 and SK2 inhibitor with IC₅₀ values of 5.3 μM and 5.0 μM, respectively. RB-042 is applicable to the research of inflammatory diseases.

ABC294735 is an orally active SK1/SK2 inhibitor. Combination of ABC294735 with Sorafenib (HY-10201) reduces pERK. ABC294735 exhibits anticancer activity against pancreatic adenocarcinoma and renal cell carcinoma. ABC294735 can be used in research related to pancreatic adenocarcinoma and renal cell carcinoma.

SphK1&2-IN-1 is a SphK inhibitor targeting to SphK1 and SphK2. SphK1&2-IN-1 has thermal stability.

SphK2-IN-1 is a SphK2 inhibitor (IC₅₀: 0.359 μM). SphK2-IN-1 can be used in the research of cancer, inflammation, neurological and cardiovascular disorders.

SphK1-IN-2 is a potent, selective SphK1 inhibitor with IC₅₀ values of 19.81 nM and ＞10 μM for SphK1 and SphK2, respectively. SphK1-IN-2 exhibits anti-proliferative activities and induces cell cycle arrest and apoptosis. SphK1-IN-2 can be used for cancer research.

SLM6031434 is a highly selective sphingosine kinase 2 (SphK2) inhibitor with an IC₅₀ value of 0.4 μM for SphK2. SLM6031434 exerts anti-fibrotic effects by increasing sphingosine accumulation and Smad7 expression. SLM6031434 demonstrates effective anti-fibrotic efficacy in a unilateral ureteral obstruction (UUO)-induced tubulointerstitial fibrosis mouse model. SLM6031434 can be used for the study of proteinuric kidney diseases or chronic kidney disease (CKD).

SLR080811 is a guanidine-based selective sphingosine kinase 2 (SphK2) inhibitor with a K_i of 1.3 μM, exhibiting ~10-fold selectivity over SphK1 (K_i = 12 μM). SLR080811 reduces sphingosine 1-phosphate (S1P) levels in vitro, but drives a SphK1-dependent increase in S1P in mice. SLR080811 can be used for cancers and fibrosis research.

(R)-FTY720-OMe is a selective SphK2 inhibitor with an IC₅₀ of 16.5  μM. (R)-FTY720-OMe can be used for cancer, fibrosis, and Alzheimer’s and sickle cell diseases research.

SphK2-IN-4 is a selective SphK2 inhibitor (IC₅₀=6.2 μM) with extremely low activity against SphK1 (IC₅₀ > 50 μM). SphK2-IN-4 exhibits broad-spectrum antiproliferative activity against colorectal cancer cells and induces apoptosis.

VT-ME6 is a selective SphK2 inhibitor with a K_i of 8 µM. VT-ME6 can be used in the research of inflammatory diseases.

SphK2-IN-5 is a selective SphK2 inhibitor with an IC₅₀ of 0.55 μM. SphK2-IN-5 exhibits anticancer activity against colon cancer and liver cancer.

SKI-II hydrochloride is an orally active dual-target inhibitor of SphK1/2 and DES1, with K_i values of 16 µM and 0.3 µM against SphK1 and DES1, respectively. SKI-II hydrochloride activates the PERK-Nrf2 antioxidant pathway by stabilizing Nrf2, and synergizes with Temozolomide (HY-17364) to induce oxidative/endoplasmic reticulum stress and cancer cell death under hypoxic conditions. SKI-II hydrochloride inhibits SphK activity, promotes ceramide accumulation and apoptosis, and synergizes with Cisplatin (HY-17394) to reverse drug resistance via the ras/MAPK pathway in vivo. SKI-II hydrochloride reduces measles virus replication by inhibiting mTORC1 activity. SKI-II hydrochloride binds to VCP to induce M1 polarization, enhances host tolerance to Staphylococcus aureus infection, and exerts radioprotective effects through Nrf2 activation and accelerated DNA repair. SKI-II hydrochloride can be used in research related to glioblastoma, acute myeloid leukemia, gastric cancer, measles virus infection, Staphylococcus aureus infection, and acute radiation syndrome.