YQ128 | CAS#2454246-18-3 | inflammasome inhibitor

MedKoo Cat#: 556036 | Name: YQ128

Description:

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

YQ128 is a potent and selective second-generation NLRP3 (NOD-like receptor P3) inflammasome inhibitor with an IC50 of 0.30 ± 0.01 μM. Further studies from in vitro and in vivo models confirmed its selective inhibition on the NLRP3 inflammasome and its brain penetration. Furthermore, pharmacokinetic studies in rats at 20 mg/kg indicated extensive systemic clearance and tissue distribution, leading to a half-life of 6.6 h. However, the oral bioavailability is estimated to be only 10%, which may reflect limited GI permeability and possibly high first-pass effects.

Chemical Structure

YQ128

CAS#2454246-18-3

Theoretical Analysis

MedKoo Cat#: 556036

Name: YQ128

CAS#: 2454246-18-3

Chemical Formula: C27H29ClN2O4S2

Exact Mass: 544.1257

Molecular Weight: 545.11

Elemental Analysis: C, 59.49; H, 5.36; Cl, 6.50; N, 5.14; O, 11.74; S, 11.76

Price and Availability

Size	Price	Availability
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,350.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,450.00	2 Weeks
2g	USD 5,650.00	2 Weeks

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Synonym

YQ128; YQ-128; YQ 128;

IUPAC/Chemical Name

N-(5-chloro-2-propoxybenzyl)-N-(4-(N-(prop-2-yn-1-yl)sulfamoyl)phenethyl)-2-(thiophen-3-yl)acetamide

InChi Key

SFPYRFRNYALLHS-UHFFFAOYSA-N

InChi Code

InChI=1S/C27H29ClN2O4S2/c1-3-13-29-36(32,33)25-8-5-21(6-9-25)11-14-30(27(31)17-22-12-16-35-20-22)19-23-18-24(28)7-10-26(23)34-15-4-2/h1,5-10,12,16,18,20,29H,4,11,13-15,17,19H2,2H3

SMILES Code

O=S(C1=CC=C(CCN(CC2=C(C=CC(Cl)=C2)OCCC)C(CC3=CSC=C3)=O)C=C1)(NCC#C)=O

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

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

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:

YQ128 is a selective second-generation NLRP3 (NOD-like receptor P3) inflammasome inhibitor with an IC50 of 0.30 µMthat significantly and selectively suppresses the production of IL-1β, but not TNF-α, and it can cross the BBB to reach the CNS.

In vitro activity:

To test whether YQ128 is a brain penetrant, its permeability and transport directionality using immortalized human cerebral microvascular endothelial cells hCMEC/D3 as the human BBB model was determined. This model expresses functional efflux transporters such as P-glycoprotein which are also expressed at the BBB; it has been widely used as a surrogate for human BBB. The potential cytotoxicity of YQ128 on hCMEC/D3 cells was first examined to rule out any potential interference with results interpretation, and the results demonstrated that YQ128 at 20 μM did not show significant toxic effects on these cells. The apical-to-basolateral (A to B) and basolateral-to-apical (B to A) Papp of 17 was 5.21 ± 0.56 × 10−6 and 1.11 ± 0.12 × 10−6 cm/sec, respectively. Thus, YQ128 exhibits an efflux ratio of 0.22, suggesting that YQ128 is not likely subject to active efflux. Reference: J Med Chem. 2019 Nov 14;62(21):9718-9731. https://pubmed.ncbi.nlm.nih.gov/31626545/

In vivo activity:

The in vivo engagement of and selectivity to the NLRP3 inflammasome by YQ128 was tested. C57BL/6 mice (n=4 per group) were pretreated with YQ128 or MCC950 (positive control) at 10 mg/kg before intraperitoneal injection of LPS, which has been shown to trigger IL-1β production in a NLRP3-dependent manner. Serum level of IL-1β was significantly reduced while no significant inhibition on the TNF-α level (Figure 6D) was observed by the treatment of both compounds at the tested dose, thus strongly suggesting the selective in vivo engagement of NLRP3 inflammasome in the observed effects by YQ128 and MCC950. Lastly, the selective inhibition on NLRP3 inflammasome by YQ128 in nlrp3−/− mice (n=3 per group) was confirmed. As expected, upon stimulation with LPS, nlrp3 deficiency abolished the production of IL-1β while the production of TNF-α is normal (Figure 6E). Treatment of nlrp3−/− mice with 17 (10 mg/kg) did not produce inhibition on the level of TNF-α and this again confirmed the selective inhibition on the NLRP3 inflammasome by our compound. Reference: J Med Chem. 2019 Nov 14;62(21):9718-9731. https://pubmed.ncbi.nlm.nih.gov/31626545/

	Solvent	mg/mL	mM
Solubility
	DMSO	175.0	321.04

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 545.11 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. Jiang Y, He L, Green J, Blevins H, Guo C, Patel SH, Halquist MS, McRae M, Venitz J, Wang XY, Zhang S. Discovery of Second-Generation NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization. J Med Chem. 2019 Nov 14;62(21):9718-9731. doi: 10.1021/acs.jmedchem.9b01155. Epub 2019 Oct 31. PMID: 31626545; PMCID: PMC6856409.

In vitro protocol:

In vivo protocol:

Jiang Y, He L, Green J, Blevins H, Guo C, Patel SH, Halquist MS, McRae M, Venitz J, Wang XY, Zhang S. Discovery of Second-Generation NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization. J Med Chem. 2019 Nov 14;62(21):9718-9731. doi: 10.1021/acs.jmedchem.9b01155. Epub 2019 Oct 31. PMID: 31626545; PMCID: PMC6856409.