SLx-2119

SLx-2119, also known as KD-025, is an orally bioavailable inhibitor of ROCK-II that is greater than 200-fold selective over ROCK-I (IC50s = 105 nM and 24 µM, respectively).

Product information

CAS Number: 911417-87-3

Molecular Weight: 452.51

Formula: C26H24N6O2

Synonym:

SLx2119

SLx 2119

KD-025

KD 025

KD025

ROCK inhibitor

Chemical Name: 2-[3-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]phenoxy]-N-(1-methylethyl)-acetamide

Smiles: CC(C)NC(=O)COC1=CC(=CC=C1)C1N=C(NC2C=C3C=NNC3=CC=2)C2=CC=CC=C2N=1

InChiKey: GKHIVNAUVKXIIY-UHFFFAOYSA-N

InChi: InChI=1S/C26H24N6O2/c1-16(2)28-24(33)15-34-20-7-5-6-17(13-20)25-30-23-9-4-3-8-21(23)26(31-25)29-19-10-11-22-18(12-19)14-27-32-22/h3-14,16H,15H2,1-2H3,(H,27,32)(H,28,33)(H,29,30,31)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

KD025 down-regulates the IL-17 and IL-21 secretion in human PBMCs, and leads to down-regulation of STAT3 phosphorylation, IRF4, and RORγt expression in CD4+ T cells. [2] KD025 inhibits the secretion of IL-21, IL-17, and IFNγ along with decreasing phosphorylated STAT3 and reduced protein expression of IRF4 and BCL6 in human peripheral blood mononuclear cells.

In Vivo:

In mice, KD025 (200 mg/kg, p.o.) inhibits ROCK activity in brain and heart, as measured by the degree of MYPT1 phosphorylation. KD025 (200 mg/kg, p.o.) significantly reduces the area of perfusion defect, and reduces tissue loss in the ipsilateral hemisphere. [1] In a collagen-induced arthritis (CIA) mouse model, KD025 (200 mg/kg, i.p.) downregulates the progression of collagen-induced arthritis via targeting of the Th17-mediated pathway. [2] KD025 ()150 mg/kg, i.p. or p.o.) effectively ameliorates cGVHD in a full MHC-mismatch model of multi-organ system cGVHD with bronchiolitis obliterans syndrome and a minor MHC-mismatch model of sclerodermatous GVHD.

References:

1. Lee JH, et al. Ann Clin Transl Neurol. 2014, 1(1), 2-14.
2. Zanin-Zhorov A, et al. Proc Natl Acad Sci U S A. 2014, 111(47), 16814-16819.
3. Flynn R, et al. Blood. 2016. pii: blood-2015-10-678706.
4. Chen W, et al. Screening RhoA/ROCK inhibitors for the ability to prevent chronic rejection of mouse cardiac allografts.Transpl Immunol. 2018 Jun 6. pii: S0966-3274(18)30029-7.

Products are for research use only. Not for human use.