SKI-178 | CAS#1259484-97-3 | SphK1 inhibitor

MedKoo Cat#: 407474 | Name: SKI-178

Description:

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

SKI-178 is a sphingosine kinase 1 (SphK1) inhibitor (IC50 = 0.1-1.8 μM). SKI-178 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. SKI-178 is a novel therapeutic agent for the treatment of AML, including multidrug-resistant/recurrent AML subtypes.

Chemical Structure

SKI-178

CAS#1259484-97-3

Theoretical Analysis

MedKoo Cat#: 407474

Name: SKI-178

CAS#: 1259484-97-3

Chemical Formula: C21H22N4O4

Exact Mass: 394.1641

Molecular Weight: 394.43

Elemental Analysis: C, 63.95; H, 5.62; N, 14.20; O, 16.22

Price and Availability

Size	Price	Availability
25mg	USD 550.00	2 Weeks
50mg	USD 950.00	2 Weeks
100mg	USD 1,650.00	2 Weeks
1g	USD 4,650.00	2 Weeks

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Synonym

SKI-178; SKI 178; SKI178.

IUPAC/Chemical Name

N'-(1-(3,4-Dimethoxyphenyl)ethylidene)-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide

InChi Key

GMFUWEBOUKIKRP-LPYMAVHISA-N

InChi Code

InChI=1S/C21H22N4O4/c1-13(15-7-10-19(28-3)20(11-15)29-4)22-25-21(26)18-12-17(23-24-18)14-5-8-16(27-2)9-6-14/h5-12H,1-4H3,(H,23,24)(H,25,26)/b22-13+

SMILES Code

O=C(C1=CC(C2=CC=C(OC)C=C2)=NN1)N/N=C(C3=CC=C(OC)C(OC)=C3)\C

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 and DMF

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-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. SKI-178 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.

In vitro activity:

SKI-178 targeting SphK1 could be a novel therapeutic agent for the treatment of acute myeloid leukemia (AML), including multidrug-resistant/recurrent AML subtypes. This study found that SKI-178 induced prolonged mitosis followed by apoptotic cell death through the intrinsic apoptotic cascade. Also, multidrug resistance did not affect the sensitivity of AML cells to SKI-178. Reference: J Pharmacol Exp Ther. 2015 Mar;352(3):494-508. https://pubmed.ncbi.nlm.nih.gov/25563902/

In vivo activity:

Targeting SphK1/2 by SKI-178 potently inhibited prostate cancer cell growth in vivo. Daily intraperitoneal injection of a single dose of SKI-178 potently inhibited PC-3 xenograft growth in nude mice. SphK inhibition, ceramide production, ATP depletion and lipid peroxidation, Akt-mTOR inactivation and JNK activation were detected in PC-3 xenograft tissues with SKI-178 administration. Reference: Cell Death Dis. 2023 Aug 21;14(8):537. https://pubmed.ncbi.nlm.nih.gov/37604912/

	Solvent	mg/mL	mM
Solubility
	DMF	25.0	63.38
	DMSO	25.0	63.38

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 394.43 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. Medina-Moctezuma ZB, Hernández-Coronado CG, Marín-López L, Guzmán A, González-Aretia D, Gutiérrez CG, Rosales-Torres AM. Sphingosine-1-phosphate regulation of luteinising hormone-induced steroidogenesis and proliferation of bovine theca cells in vitro. Reprod Fertil Dev. 2023 Jun;35(9):518-526. doi: 10.1071/RD22289. PMID: 37225163. 2. Dick TE, Hengst JA, Fox TE, Colledge AL, Kale VP, Sung SS, Sharma A, Amin S, Loughran TP Jr, Kester M, Wang HG, Yun JK. The apoptotic mechanism of action of the sphingosine kinase 1 selective inhibitor SKI-178 in human acute myeloid leukemia cell lines. J Pharmacol Exp Ther. 2015 Mar;352(3):494-508. doi: 10.1124/jpet.114.219659. Epub 2015 Jan 6. PMID: 25563902; PMCID: PMC4352591. 3. Jin L, Zhu J, Yao L, Shen G, Xue BX, Tao W. Targeting SphK1/2 by SKI-178 inhibits prostate cancer cell growth. Cell Death Dis. 2023 Aug 21;14(8):537. doi: 10.1038/s41419-023-06023-4. PMID: 37604912; PMCID: PMC10442381. 4. Hengst JA, Dick TE, Sharma A, Doi K, Hegde S, Tan SF, Geffert LM, Fox TE, Sharma AK, Desai D, Amin S, Kester M, Loughran TP, Paulson RF, Claxton DF, Wang HG, Yun JK. SKI-178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models. Cancer Transl Med. 2017 Jul-Aug;3(4):109-121. doi: 10.4103/ctm.ctm_7_17. Epub 2017 Aug 14. PMID: 28890935; PMCID: PMC5590228.

In vitro protocol:

In vivo protocol:

1. Jin L, Zhu J, Yao L, Shen G, Xue BX, Tao W. Targeting SphK1/2 by SKI-178 inhibits prostate cancer cell growth. Cell Death Dis. 2023 Aug 21;14(8):537. doi: 10.1038/s41419-023-06023-4. PMID: 37604912; PMCID: PMC10442381. 2. Hengst JA, Dick TE, Sharma A, Doi K, Hegde S, Tan SF, Geffert LM, Fox TE, Sharma AK, Desai D, Amin S, Kester M, Loughran TP, Paulson RF, Claxton DF, Wang HG, Yun JK. SKI-178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models. Cancer Transl Med. 2017 Jul-Aug;3(4):109-121. doi: 10.4103/ctm.ctm_7_17. Epub 2017 Aug 14. PMID: 28890935; PMCID: PMC5590228.

1: González-Aretia D, Hernández-Coronado CG, Guzmán A, Medina-Moctezuma ZB, Gutiérrez CG, Rosales-Torres AM. Sphingosine-1-phosphate mediates FSH-induced cell viability but not steroidogenesis in bovine granulosa cells. Theriogenology. 2024 Jan 1;213:90-96. doi: 10.1016/j.theriogenology.2023.10.003. Epub 2023 Oct 5. PMID: 37820497. 2: Jin L, Zhu J, Yao L, Shen G, Xue BX, Tao W. Targeting SphK1/2 by SKI-178 inhibits prostate cancer cell growth. Cell Death Dis. 2023 Aug 21;14(8):537. doi: 10.1038/s41419-023-06023-4. PMID: 37604912; PMCID: PMC10442381. 3: Medina-Moctezuma ZB, Hernández-Coronado CG, Marín-López L, Guzmán A, González-Aretia D, Gutiérrez CG, Rosales-Torres AM. Sphingosine-1-phosphate regulation of luteinising hormone-induced steroidogenesis and proliferation of bovine theca cells in vitro. Reprod Fertil Dev. 2023 Jun;35(9):518-526. doi: 10.1071/RD22289. PMID: 37225163. 4: Hengst JA, Hegde S, Paulson RF, Yun JK. Development of SKI-349, a dual- targeted inhibitor of sphingosine kinase and microtubule polymerization. Bioorg Med Chem Lett. 2020 Oct 15;30(20):127453. doi: 10.1016/j.bmcl.2020.127453. Epub 2020 Jul 28. PMID: 32736077; PMCID: PMC7541634. 5: Alshaker H, Srivats S, Monteil D, Wang Q, Low CMR, Pchejetski D. Field template-based design and biological evaluation of new sphingosine kinase 1 inhibitors. Breast Cancer Res Treat. 2018 Nov;172(1):33-43. doi: 10.1007/s10549-018-4900-1. Epub 2018 Jul 24. PMID: 30043096; PMCID: PMC6208908. 6: Hengst JA, Dick TE, Sharma A, Doi K, Hegde S, Tan SF, Geffert LM, Fox TE, Sharma AK, Desai D, Amin S, Kester M, Loughran TP, Paulson RF, Claxton DF, Wang HG, Yun JK. SKI-178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models. Cancer Transl Med. 2017 Jul-Aug;3(4):109-121. doi: 10.4103/ctm.ctm_7_17. Epub 2017 Aug 14. PMID: 28890935; PMCID: PMC5590228. 7: LeBlanc FR, Liu X, Hengst J, Fox T, Calvert V, Petricoin EF 3rd, Yun J, Feith DJ, Loughran TP Jr. Sphingosine kinase inhibitors decrease viability and induce cell death in natural killer-large granular lymphocyte leukemia. Cancer Biol Ther. 2015;16(12):1830-40. doi: 10.1080/15384047.2015.1078949. PMID: 26252351; PMCID: PMC4847818. 8: Dick TE, Hengst JA, Fox TE, Colledge AL, Kale VP, Sung SS, Sharma A, Amin S, Loughran TP Jr, Kester M, Wang HG, Yun JK. The apoptotic mechanism of action of the sphingosine kinase 1 selective inhibitor SKI-178 in human acute myeloid leukemia cell lines. J Pharmacol Exp Ther. 2015 Mar;352(3):494-508. doi: 10.1124/jpet.114.219659. Epub 2015 Jan 6. PMID: 25563902; PMCID: PMC4352591. 9: Hengst JA, Wang X, Sk UH, Sharma AK, Amin S, Yun JK. Development of a sphingosine kinase 1 specific small-molecule inhibitor. Bioorg Med Chem Lett. 2010 Dec 15;20(24):7498-502. doi: 10.1016/j.bmcl.2010.10.005. Epub 2010 Nov 1. PMID: 21050755.

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MedKoo CAT#: 146230

CAS#: 1966-58-1