1259484-97-3

1259484-97-3 structure

Name: SKI-178
Chemical Name: N'-[1-(3,4-dimethoxyphenyl)ethylidene]-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide
CAS Number: 1259484-97-3
Molecular Formula: C₂₁H₂₂N₄O₄
Molecular Weight: 394.42400
Catalog: Signaling Pathways Apoptosis Apoptosis
Create Date: 2018-04-13 05:57:35
Modify Date: 2024-01-14 09:11:58
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 drug sensitive and multi-drug resistant cancer cell lines (i.e., MTR3, NCI-ADR and HL60/VCR). SKI-178 induces apoptosis in a CDK1-dependent manner in human acute myeloid leukemia cell lines[1][2].

Name	N'-[1-(3,4-dimethoxyphenyl)ethylidene]-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide

Description	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 drug sensitive and multi-drug resistant cancer cell lines (i.e., MTR3, NCI-ADR and HL60/VCR). SKI-178 induces apoptosis in a CDK1-dependent manner in human acute myeloid leukemia cell lines[1][2].
Related Catalog	Signaling Pathways >> Apoptosis >> Apoptosis Research Areas >> Cancer Signaling Pathways >> Immunology/Inflammation >> SPHK
In Vitro	SKI-178 (5 μM; 24 hours)-induced apoptotic cell death correlates with prolonged Bcl-2 phosphorylation[1]. Apoptosis Analysis[1] Cell Line: HL-60 cells Concentration: 5 μM Incubation Time: 24 hours Result: JNK activity (indicated by phosphorylation at Thr183/Tyr185) increased in a time-dependent manner starting as early as 2 hours continued to increase for at least 24 hours. There was a concomitant increase in apoptotic cell death indicated by the cleavage of caspase-7. Bcl-2 phosphorylation at Ser70 increased with time in response to SKI-178 treatment, reaching maximal levels at 8 hours, which was consistent with the timing of caspase-7 activation.
In Vivo	SKI-178 (20mg/kg; retro-orbital injection under isoflurane anesthesia) inhibits leukemic progression in the MLL-AF9 model[3]. Animal Model: MLL-AF9 mouse model (leukemic mice)[3] Dosage: 20 mg/kg Administration: Retro-orbital injection under isoflurane anesthesia; three times per week for 1 and 3 weeks Result: White blood cell (WBC) counts decreased from their initial 104 cells/μL levels and continued to decline after 3 weeks of treatment until they reached normal levels (~4×103 cells/μL).
References	[1]. Hengst JA, et al. SKI-178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models. Cancer Transl Med. 2017;3(4):109-121. [2]. Hengst JA, et al. Development of a sphingosine kinase 1 specific small-molecule inhibitor. Bioorg Med Chem Lett. 2010;20(24):7498-7502. [3]. Dick TE, et al. 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;352(3):494-508.

Molecular Formula	C₂₁H₂₂N₄O₄
Molecular Weight	394.42400
Exact Mass	394.16400
PSA	97.83000
LogP	3.64740

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