SKI-II | CAS#312636-16-1 | sphingosine kinase inhibitior

MedKoo Cat#: 407255 | Name: SKI-II

Description:

WARNING: This product is for research use only, not for human or veterinary use.

SKI-II is a selective non-lipid inhibitor of sphingosine kinase (IC50 = 0.5 μM). It inhibits acute myelogenous leukemia cell growth in vitro and in vivo. SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, and concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells.

Chemical Structure

SKI-II

CAS#312636-16-1

Theoretical Analysis

MedKoo Cat#: 407255

Name: SKI-II

CAS#: 312636-16-1

Chemical Formula: C15H11ClN2OS

Exact Mass: 302.0281

Molecular Weight: 302.78

Elemental Analysis: C, 59.50; H, 3.66; Cl, 11.71; N, 9.25; O, 5.28; S, 10.59

Price and Availability

Size	Price	Availability
10mg	USD 285.00	2 Weeks
25mg	USD 450.00	2 Weeks
50mg	USD 750.00	2 Weeks
100mg	USD 1,250.00	2 Weeks
200mg	USD 1,950.00	2 Weeks

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Synonym

SKI-II; SKI II. Sphingosine kinase inhibitor II;

IUPAC/Chemical Name

4-[[4-(4-Chlorophenyl)-2-thiazolyl]amino]phenol

InChi Key

ZFGXZJKLOFCECI-UHFFFAOYSA-N

InChi Code

InChI=1S/C15H11ClN2OS/c16-11-3-1-10(2-4-11)14-9-20-15(18-14)17-12-5-7-13(19)8-6-12/h1-9,19H,(H,17,18)

SMILES Code

OC1=CC=C(NC2=NC(C3=CC=C(Cl)C=C3)=CS2)C=C1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

SKI-II is a selective non-lipid inhibitor of sphingosine kinase (IC50 = 0.5 μM); does not act at ATP-binding site. Displays no inhibition of ERK2, PI 3-kinase, or PKCα at concentrations up to 60 μM. Reduces levels of sphingosine-1-phosphate in MDA-MB-231 breast cancer cells. Induces apoptosis and inhibits proliferation in several other tumor cell lines in vitro (IC50 = 0.9 - 4.6 μM).

In vitro activity:

SKI-II might be a promising anti-acute myeloid leukemia (AML) agent. SKI-II was more efficient than two known SphK1 inhibitors (SK1-I and FTY720) in inhibiting AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. Reference: Biochem Biophys Res Commun. 2015 May 15;460(4):903-8. https://pubmed.ncbi.nlm.nih.gov/25824043/

In vivo activity:

This study found that SKI-II treatment significantly reduced plasma sphingosine 1-phosphate (S1P) levels associated with high-density lipoproteins (HDL). SKI-II treatment increased atherosclerotic lesions in the thoracic aorta in mice on high but not low cholesterol diet. SKI-II did not affect body weight, blood cell counts and plasma total and HDL cholesterol, but decreased triglycerides. Mice on high cholesterol diet receiving SKI-II showed elevated levels of tumor necrosis factor-α and endothelial adhesion molecules. Reference: Atherosclerosis. 2015 May;240(1):212-5. https://pubmed.ncbi.nlm.nih.gov/25801013/

	Solvent	mg/mL	mM
Solubility
	DMSO	30.3	100.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 302.78 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Yang L, Weng W, Sun ZX, Fu XJ, Ma J, Zhuang WF. SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo. Biochem Biophys Res Commun. 2015 May 15;460(4):903-8. doi: 10.1016/j.bbrc.2015.03.114. Epub 2015 Mar 28. PMID: 25824043. 2. Li PH, Wu JX, Zheng JN, Pei DS. A sphingosine kinase-1 inhibitor, SKI-II, induces growth inhibition and apoptosis in human gastric cancer cells. Asian Pac J Cancer Prev. 2014;15(23):10381-5. doi: 10.7314/apjcp.2014.15.23.10381. PMID: 25556479. 3. Potì F, Ceglarek U, Burkhardt R, Simoni M, Nofer JR. SKI-II--a sphingosine kinase 1 inhibitor--exacerbates atherosclerosis in low-density lipoprotein receptor-deficient (LDL-R-/-) mice on high cholesterol diet. Atherosclerosis. 2015 May;240(1):212-5. doi: 10.1016/j.atherosclerosis.2015.03.020. Epub 2015 Mar 16. PMID: 25801013. 4. Chiba Y, Takeuchi H, Sakai H, Misawa M. SKI-II, an inhibitor of sphingosine kinase, ameliorates antigen-induced bronchial smooth muscle hyperresponsiveness, but not airway inflammation, in mice. J Pharmacol Sci. 2010;114(3):304-10. doi: 10.1254/jphs.10202fp. Epub 2010 Oct 8. PMID: 20948165.

In vitro protocol:

In vivo protocol:

1. Potì F, Ceglarek U, Burkhardt R, Simoni M, Nofer JR. SKI-II--a sphingosine kinase 1 inhibitor--exacerbates atherosclerosis in low-density lipoprotein receptor-deficient (LDL-R-/-) mice on high cholesterol diet. Atherosclerosis. 2015 May;240(1):212-5. doi: 10.1016/j.atherosclerosis.2015.03.020. Epub 2015 Mar 16. PMID: 25801013. 2. Chiba Y, Takeuchi H, Sakai H, Misawa M. SKI-II, an inhibitor of sphingosine kinase, ameliorates antigen-induced bronchial smooth muscle hyperresponsiveness, but not airway inflammation, in mice. J Pharmacol Sci. 2010;114(3):304-10. doi: 10.1254/jphs.10202fp. Epub 2010 Oct 8. PMID: 20948165.

1: Prell A, Wigger D, Huwiler A, Schumacher F, Kleuser B. The sphingosine kinase 2 inhibitors ABC294640 and K145 elevate (dihydro)sphingosine 1-phosphate levels in various cells. J Lipid Res. 2024 Aug 23;65(10):100631. doi: 10.1016/j.jlr.2024.100631. Epub ahead of print. PMID: 39182604; PMCID: PMC11465068. 2: Nguyen Van Long F, Le T, Caron P, Valcourt-Gendron D, Sergerie R, Laverdière I, Vanura K, Guillemette C. Targeting sphingolipid metabolism in chronic lymphocytic leukemia. Clin Exp Med. 2024 Jul 30;24(1):174. doi: 10.1007/s10238-024-01440-x. PMID: 39078421; PMCID: PMC11289351. 3: Nojima H, Shimizu H, Murakami T, Shuto K, Koda K. Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy. Cancers (Basel). 2024 Feb 20;16(5):850. doi: 10.3390/cancers16050850. PMID: 38473211; PMCID: PMC10931359. 4: Wang X, Li B, Yu X, Zhou Y, Wang K, Gao Y. Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells. Mol Med Rep. 2024 Jan;29(1):16. doi: 10.3892/mmr.2023.13139. Epub 2023 Dec 8. PMID: 38063180; PMCID: PMC10716814. 5: Zwölfer M, Heinrich D, Wandt B, Rhodin H, Spörri J, Nachbauer W. A graph- based approach can improve keypoint detection of complex poses: a proof-of- concept on injury occurrences in alpine ski racing. Sci Rep. 2023 Dec 5;13(1):21465. doi: 10.1038/s41598-023-47875-2. PMID: 38052814; PMCID: PMC10697942. 6: Sousa N, Geiß C, Bindila L, Lieberwirth I, Kim E, Régnier-Vigouroux A. Targeting sphingolipid metabolism with the sphingosine kinase inhibitor SKI-II overcomes hypoxia-induced chemotherapy resistance in glioblastoma cells: effects on cell death, self-renewal, and invasion. BMC Cancer. 2023 Aug 16;23(1):762. doi: 10.1186/s12885-023-11271-w. PMID: 37587449; PMCID: PMC10433583. 7: Sarapura Martinez VJ, Buonincontro B, Cassarino C, Bernatowiez J, Colado A, Cordini G, Custidiano MDR, Mahuad C, Pavlovsky MA, Bezares RF, Favale NO, Vermeulen M, Borge M, Giordano M, Gamberale R. Venetoclax resistance induced by activated T cells can be counteracted by sphingosine kinase inhibitors in chronic lymphocytic leukemia. Front Oncol. 2023 Mar 20;13:1143881. doi: 10.3389/fonc.2023.1143881. PMID: 37020867; PMCID: PMC10067719. 8: Li Q, Shi Y, Li X, Yang Y, Zhang X, Xu L, Ma Z, Wang J, Fan L, Wu L. Proteomic-Based Approach Reveals the Involvement of Apolipoprotein A-I in Related Phenotypes of Autism Spectrum Disorder in the BTBR Mouse Model. Int J Mol Sci. 2022 Dec 4;23(23):15290. doi: 10.3390/ijms232315290. PMID: 36499620; PMCID: PMC9737945. 9: Yuan F, Hao X, Cui Y, Huang F, Zhang X, Sun Y, Hao T, Wang Z, Xia W, Su Y, Zhang M. SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation. Cell Death Dis. 2022 Nov 17;13(11):963. doi: 10.1038/s41419-022-05415-2. PMID: 36396932; PMCID: PMC9671891. 10: Chithelen J, Franke H, Länder N, Grafen A, Schneider-Schaulies J. The Sphingolipid Inhibitors Ceranib-2 and SKI-II Reduce Measles Virus Replication in Primary Human Lymphocytes: Effects on mTORC1 Downstream Signaling. Front Physiol. 2022 Mar 17;13:856143. doi: 10.3389/fphys.2022.856143. PMID: 35370781; PMCID: PMC8968423. 11: Castell AL, Vivoli A, Tippetts TS, Frayne IR, Angeles ZE, Moullé VS, Campbell SA, Ruiz M, Ghislain J, Des Rosiers C, Holland WL, Summers SA, Poitout V. Very-Long-Chain Unsaturated Sphingolipids Mediate Oleate-Induced Rat β-Cell Proliferation. Diabetes. 2022 Jun 1;71(6):1218-1232. doi: 10.2337/db21-0640. PMID: 35287172; PMCID: PMC9163557. 12: Ye AF, Liu XC, Chen LJ, Xia YP, Yang XB, Sun WJ. Endogenous Ca2+ release was involved in 50-Hz MF-induced proliferation via Akt-SK1 signal cascade in human amniotic epithelial cells. Electromagn Biol Med. 2022 Apr 3;41(2):142-151. doi: 10.1080/15368378.2022.2031211. Epub 2022 Feb 7. PMID: 35129008. 13: Ersöz NŞ, Adan A. Resveratrol triggers anti-proliferative and apoptotic effects in FLT3-ITD-positive acute myeloid leukemia cells via inhibiting ceramide catabolism enzymes. Med Oncol. 2022 Jan 20;39(3):35. doi: 10.1007/s12032-021-01627-2. PMID: 35059910. 14: Oğuz O, Adan A. Involvement of Sphingolipid Metabolism Enzymes in Resveratrol-Mediated Cytotoxicity in Philadelphia-Positive Acute Lymphoblastic Leukemia. Nutr Cancer. 2022;74(7):2508-2521. doi: 10.1080/01635581.2021.2005806. Epub 2021 Nov 22. PMID: 34806508. 15: Companioni O, Mir C, Garcia-Mayea Y, LLeonart ME. Targeting Sphingolipids for Cancer Therapy. Front Oncol. 2021 Oct 19;11:745092. doi: 10.3389/fonc.2021.745092. PMID: 34737957; PMCID: PMC8560795. 16: Chahar KR, Kumar V, Sharma PK, Brünnert D, Kaushik V, Gehlot P, Shekhawat I, Kumar S, Sharma AK, Kumari S, Goyal P. Sphingosine kinases negatively regulate the expression of matrix metalloproteases (MMP1 and MMP3) and their inhibitor TIMP3 genes via sphingosine 1-phosphate in extravillous trophoblasts. Reprod Med Biol. 2021 Mar 22;20(3):267-276. doi: 10.1002/rmb2.12379. PMID: 34262394; PMCID: PMC8254167. 17: Sun D, Wang S. Sphingosine kinases are involved in the regulation of all- trans retinoic acid sensitivity of K562 chronic myeloid leukemia cells. Oncol Lett. 2021 Aug;22(2):581. doi: 10.3892/ol.2021.12842. Epub 2021 Jun 2. PMID: 34122632; PMCID: PMC8190775. 18: Corman A, Kanellis DC, Michalska P, Häggblad M, Lafarga V, Bartek J, Carreras-Puigvert J, Fernandez-Capetillo O. A chemical screen for modulators of mRNA translation identifies a distinct mechanism of toxicity for sphingosine kinase inhibitors. PLoS Biol. 2021 May 25;19(5):e3001263. doi: 10.1371/journal.pbio.3001263. PMID: 34033645; PMCID: PMC8183993. 19: Sah DK, Rai Y, Chauhan A, Kumari N, Chaturvedi MM, Bhatt AN. Sphingosine kinase inhibitor, SKI-II confers protection against the ionizing radiation by maintaining redox homeostasis most likely through Nrf2 signaling. Life Sci. 2021 Aug 1;278:119543. doi: 10.1016/j.lfs.2021.119543. Epub 2021 Apr 30. PMID: 33933460. 20: Li Y, Gao Y, Liang B, Nie W, Zhao L, Wang L. Combined effects on leukemia cell growth by targeting sphingosine kinase 1 and sirtuin 1 signaling. Exp Ther Med. 2020 Dec;20(6):262. doi: 10.3892/etm.2020.9392. Epub 2020 Oct 27. PMID: 33199987; PMCID: PMC7664611.