sphingosine kinase

Phorbol 12-myristate 13-acetate (PMA) is a natural phorbol ester that acts as an activator of PKC, SphK, and NF-κB, and is commonly used to induce differentiation of THP-1 cells and establish dermatitis models.

K145 hydrochloride is a selective sphk2 inhibitor with substrate competitiveness and oral activity, with IC₅₀ of 4.3 µM and Ki of 6.4 µM. K145 hydrochloride can induce apoptosis and has strong antitumor activity.

MP-A08 is a highly selective, ATP-competitive inhibitor of sphingosine kinase (SPHK1) that targets both SphK1 and SphK2 [Ki: 6.9 ± 0.8 μM and 27 ± 3 μM, respectively].

MK-571 sodium (L-660711 sodium salt) is a selective, orally active antagonist of the CysLT1 receptor. MK-571 sodium is a multidrug resistance protein-2 (ABCC2, Mrp2) inhibitor used to demonstrate the role of Mrp2 in the cellular efflux of drugs, xenobiotics, and their conjugates. MK-571 sodium can inhibit the synthesis of K-4′-O-GlcA (19.7 μM). MK571 dose-dependently inhibits the intracellular biosynthesis of all flavonol sulphates and glucuronides by Caco-2 cells. MK-571 sodium significantly inhibits phase-2 conjugation of kaempferol by cell-free extracts of Caco-2, and production of kaempferol-4′-O-glucuronide was competitively inhibited. In addition to inhibiting MRP2, MK571 is a potent inhibitor of enterocyte phase-2 conjugation.

Methyl caprooyl tyrosinate (MHP) is an activator of sphingosine kinase (SPHK1) and significantly stimulates CAMP mRNA and protein production in KC.

PF-543 (Sphingosine Kinase 1 Inhibitor II), a novel sphingosine-competitive inhibitor of SphK1, inhibits SphK1 with IC₅₀ of 2.0 nM and Ki of 3.6 nM.

SKI II (SphK-I2) is a highly selective and non-ATP-competitive S1P receptor inhibitor (IC₅₀: 0.5 μM) while exhibiting no inhibitory action on other kinases including PKCα, PI3K, and ERK2.

Opaganib (ABC294640) is an orally active and specific sphingosine kinase-2 (SphK2) inhibitor (IC₅₀: 60 μM).

SKI V is a potent and noncompetitive non-lipid sphingosine kinase (SPHK; SK) inhibitor (GST-hSK,IC₅₀ : 2 μM), and is a PI3K inhibitor(hPI3k,IC₅₀ : 6 μM), induces apoptosis and has antitumor activity

PF-543 hydrochloride (PF-543) inhibits SphK1 with a K(i) of 3.6 nM, is sphingosine-competitive and is more than 100-fold selective for SphK1 over the SphK2 isoform.

SKI-178 is a sphingosine kinase 1 (SphK1) inhibitor with IC₅₀ of 0.1-1.8 μM. It induces prolonged mitosis followed by apoptotic cell death through the intrinsic apoptotic cascade. The sustained activation of CDK1 during prolonged mitosis, mediated by SKI-178 leads to the simultaneous phosphorylation of the prosurvival Bcl-2 family members, Bcl-2 and Bcl-xl, as well as the phosphorylation and subsequent degradation of Mcl-1.

Peretinoin (NIK333) is an oral acyclic retinoid with a vitamin A-like structure that targets retinoid nuclear receptors such as RXR and RAR.

PF-543 Citrate (Sphingosine Kinase 1 Inhibitor II Citrate) is a selective and potent inhibitor of sphingosine kinase 1 (SPHK1) and is an efficient inhibitor of 1-phosphate sphingosine (S1P) formation. It possesses anticancer, antifibrotic, and anti-inflammatory activities and can be used in research on colorectal cancer.

SLP9101555 is a potent and selective sphingosine kinase 2 (SphK2) inhibitor with a Ki of 90 nM.SLP9101555 has a high affinity for SphK2, which is 200-fold higher than that of SphK1.SLP9101555 dramatically reduces extracellular S1P sphingosine 1-phosphate (S1P) levels.

Iso-SLR 080811 is an isomer of SLR 080811, suitable for relevant research in the life sciences. SLR080811 is a selective SphK2 inhibitor (Ki=1.3 μM) that elevates blood S1P levels in wild-type mice, reduces S1P levels in sphk1 knockout mice, and leaves S1P levels unchanged in SphK2 knockout mice.

SphK1&2-IN-1, a sphingosine kinase inhibitor, exhibits anti-inflammatory, antitumor, and hemostatic properties.

N-Desmethyltamoxifen hydrochloride is the primary metabolite of tamoxifen in humans.

N-Desmethyltamoxifen, the principal metabolite of tamoxifen in humans, serves as an efficacious modulator of ceramide metabolism within human AML cells by inhibiting ceramide glycosylation, hydrolysis, and sphingosine phosphorylation. Although it demonstrates weak antiestrogenic properties, it acts as a protein kinase C (PKC) inhibitor with a potency ten times greater than that of tamoxifen.

SK1-IN-1 is an orally available and potent sphingosine kinase 1 (SPHK1) inhibitor (IC₅₀: 58 nM), with potential anticancer activity, and can be used to study cancer and neurodegenerative diseases.

(R)-AAL is an immunomodulatory agent with an ID50 of 0.009 mg/kg for reducing circulating T lymphocytes in rats. It also acts as a substrate for sphingosine kinase (SphK), which catalyzes the phosphorylation of (R)-AAL.

SphK2-IN-3 (compound 12q) is a selective sphingosine kinase 2 inhibitor. It exhibits antiproliferative effects on various cancer cells and can induce G2 phase arrest and apoptosis in HepG2 liver cancer cells.

SLR080811 is a guanidine-based selective inhibitor of sphingosine kinase 2 (SphK2) with a Ki value of 1.3 μM, demonstrating approximately 10-fold selectivity over SphK1 (Ki = 12 μM). In vitro, it reduces sphingosine-1-phosphate (S1P) levels, but in mice, it can induce SphK1-dependent S1P level increases. SLR080811 is applicable in cancer and fibrosis research.

L-threo-Sphingosine C-18 is a protein kinase C inhibitor.

N,N-Dimethylsphingosine, an endogenous metabolite, is a potent competitive sphingosine kinase (SphK) inhibitor that selectively inhibits sphingosine phosphorylation without affecting its N-acylation.DMS is elevated in models of neuropathic pain, and may mediate mechanical nociception by increasing the release of IL-1β and MCP-1.