SLM6031434 HCl | CAS#1897379-34-8 | 1897379-33-7 | SphK2-selective inhibitor

MedKoo Cat#: 530617 | Name: SLM6031434 HCl

Featured

Description:

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

SLM6031434 is a SphK2-selective inhibitor.

Chemical Structure

SLM6031434 HCl

CAS#1897379-34-8 (HCl)

Theoretical Analysis

MedKoo Cat#: 530617

Name: SLM6031434 HCl

CAS#: 1897379-34-8 (HCl)

Chemical Formula: C22H31ClF3N5O2

Exact Mass: 0.0000

Molecular Weight: 489.97

Elemental Analysis: C, 53.93; H, 6.38; Cl, 7.24; F, 11.63; N, 14.29; O, 6.53

Price and Availability

Size	Price	Availability
5mg	USD 450.00	2 Weeks
10mg	USD 750.00	2 Weeks
25mg	USD 1,650.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

1897379-34-8 (HCl) 1897379-33-7 (free base) 1897381-17-7 (free base)

Synonym

SLM6031434 HCl; SLM-6031434 HCl; SLM 6031434 HCl; SLM-6031434 hydrochloride

IUPAC/Chemical Name

(S)-2-(3-(4-(octyloxy)-3-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide hydrochloride

InChi Key

YIGAQKBPLMSWOD-LMOVPXPDSA-N

InChi Code

InChI=1S/C22H30F3N5O2.ClH/c1-2-3-4-5-6-7-13-31-18-11-10-15(14-16(18)22(23,24)25)19-28-20(32-29-19)17-9-8-12-30(17)21(26)27;/h10-11,14,17H,2-9,12-13H2,1H3,(H3,26,27);1H/t17-;/m0./s1

SMILES Code

N=C(N1CCC[C@H]1C2=NC(C3=CC=C(C(C(F)(F)F)=C3)OCCCCCCCC)=NO2)N.[H]Cl

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

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

Certificate of Analysis

View CoA: current batch, Lot#T20O09R24

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SLM6031434 is a SPHK2 inhibitor (Ki = 0.4 μM for the recombinant mouse enzyme). It is selective for SPHK2 over SPHK1 (Kis = >20 μM). It decreases S1P and increases sphingosine levels in U937 monocytic leukemia cells in a concentration-dependent manner. SLM6031434 reduces blood S1P levels in Sphk1-/-, but not Sphk2-/-, mice. SLM6031434 also increases blood S1P levels in wild-type mice and rats.

In vitro activity:

This study found that SphK2 plays a pro-inflammatory role in microglia, and inhibiting it with SLM6031434 contributed to suppressing inflammatory responses. Inhibiting SphK2 with SLM6031434 significantly reduced the lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) in BV2 mouse microglia cells. Reference: Int J Mol Sci. 2023 May 9;24(10):8508. https://pubmed.ncbi.nlm.nih.gov/37239854/

In vivo activity:

This study suggests that SK2 inhibition has anti-fibrotic effects, making it a promising target for treating fibrosis in chronic kidney disease. In a mouse model of progressive kidney damage, results showed that mice treated with SLM6031434 and HWG-35D exhibited reduced fibrotic responses compared to those treated with a vehicle control. In SLM6031434 and HWG-35D treated mice, there was decreased collagen accumulation and lower expression of key fibrosis-related proteins. Reference: Cell Signal. 2021 Mar;79:109881. https://pubmed.ncbi.nlm.nih.gov/33301900/

	Solvent	mg/mL	mM
Solubility
	DMSO	49.0	100.00
	Water	9.8	20.00

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 489.97 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. Standoli S, Rapino C, Di Meo C, Rudowski A, Kämpfer-Kolb N, Volk LM, Thomas D, Trautmann S, Schreiber Y, Meyer Zu Heringdorf D, Maccarrone M. Sphingosine Kinases at the Intersection of Pro-Inflammatory LPS and Anti-Inflammatory Endocannabinoid Signaling in BV2 Mouse Microglia Cells. Int J Mol Sci. 2023 May 9;24(10):8508. doi: 10.3390/ijms24108508. PMID: 37239854; PMCID: PMC10217805. 2. Schwalm S, Beyer S, Hafizi R, Trautmann S, Geisslinger G, Adams DR, Pyne S, Pyne N, Schaefer L, Huwiler A, Pfeilschifter J. Validation of highly selective sphingosine kinase 2 inhibitors SLM6031434 and HWG-35D as effective anti-fibrotic treatment options in a mouse model of tubulointerstitial fibrosis. Cell Signal. 2021 Mar;79:109881. doi: 10.1016/j.cellsig.2020.109881. Epub 2020 Dec 8. PMID: 33301900.

In vitro protocol:

In vivo protocol:

1. Schwalm S, Beyer S, Hafizi R, Trautmann S, Geisslinger G, Adams DR, Pyne S, Pyne N, Schaefer L, Huwiler A, Pfeilschifter J. Validation of highly selective sphingosine kinase 2 inhibitors SLM6031434 and HWG-35D as effective anti-fibrotic treatment options in a mouse model of tubulointerstitial fibrosis. Cell Signal. 2021 Mar;79:109881. doi: 10.1016/j.cellsig.2020.109881. Epub 2020 Dec 8. PMID: 33301900.

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 Oct;65(10):100631. doi: 10.1016/j.jlr.2024.100631. Epub 2024 Aug 23. PMID: 39182604; PMCID: PMC11465068. 2: Wallen TE, Morris M, Ammann A, Baucom MR, Price A, Schuster R, Makley AT, Goodman MD. Platelet Function is Independent of Sphingolipid Manipulation. J Surg Res. 2024 Aug;300:25-32. doi: 10.1016/j.jss.2024.04.063. Epub 2024 May 24. PMID: 38795670. 3: Standoli S, Rapino C, Di Meo C, Rudowski A, Kämpfer-Kolb N, Volk LM, Thomas D, Trautmann S, Schreiber Y, Meyer Zu Heringdorf D, Maccarrone M. Sphingosine Kinases at the Intersection of Pro-Inflammatory LPS and Anti-Inflammatory Endocannabinoid Signaling in BV2 Mouse Microglia Cells. Int J Mol Sci. 2023 May 9;24(10):8508. doi: 10.3390/ijms24108508. PMID: 37239854; PMCID: PMC10217805. 4: Imeri F, Stepanovska Tanturovska B, Schwalm S, Saha S, Zeng-Brouwers J, Pavenstädt H, Pfeilschifter J, Schaefer L, Huwiler A. Loss of sphingosine kinase 2 enhances Wilm's tumor suppressor gene 1 and nephrin expression in podocytes and protects from streptozotocin-induced podocytopathy and albuminuria in mice. Matrix Biol. 2021 Apr;98:32-48. doi: 10.1016/j.matbio.2021.05.003. Epub 2021 May 17. PMID: 34015468. 5: Schwalm S, Beyer S, Hafizi R, Trautmann S, Geisslinger G, Adams DR, Pyne S, Pyne N, Schaefer L, Huwiler A, Pfeilschifter J. Validation of highly selective sphingosine kinase 2 inhibitors SLM6031434 and HWG-35D as effective anti- fibrotic treatment options in a mouse model of tubulointerstitial fibrosis. Cell Signal. 2021 Mar;79:109881. doi: 10.1016/j.cellsig.2020.109881. Epub 2020 Dec 8. PMID: 33301900. 6: Sibley CD, Morris EA, Kharel Y, Brown AM, Huang T, Bevan DR, Lynch KR, Santos WL. Discovery of a Small Side Cavity in Sphingosine Kinase 2 that Enhances Inhibitor Potency and Selectivity. J Med Chem. 2020 Feb 13;63(3):1178-1198. doi: 10.1021/acs.jmedchem.9b01508. Epub 2020 Jan 28. PMID: 31895563; PMCID: PMC8215855.