(3S)-N-[3-Hydroxy-5-[(1,4,5,6-tetrahydro-5-hydroxy-2-pyriMidinyl)aMino] benzoyl]glycyl-3-(3-broMo-5-t-butylphenyl)-beta-alanine

Product Name(3S)-N-[3-Hydroxy-5-[(1,4,5,6-tetrahydro-5-hydroxy-2-pyriMidinyl)aMino] benzoyl]glycyl-3-(3-broMo-5-t-butylphenyl)-beta-alanine
CAS1564286-55-0
MFC26H32BrN5O6
MW590.47
EINECS200-110-4
MOL File1564286-55-0.mol

Chemical Properties

Density	1.52±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMSO : 10.5 mg/mL (17.78 mM; Need ultrasonic and warming);
form	Powder
pka	4.10±0.10(Predicted)
color	White to light brown
InChIKey	CHDFBRXDZCBZFZ-DLINEHSKNA-N
SMILES	C(O)(=O)[C@@H](C1=CC(C(C)(C)C)=CC(Br)=C1)CN(C(=O)CN)C(=O)C1=CC(NC2NCC(O)CN=2)=CC(O)=C1 \|&1:3,r\|

Usage And Synthesis

Description

CWHM12 is an analog of RGD peptide , a tripeptide that inhibits integrin-ligand interactions in studies related to cell adhesion, migration, growth, and differentiation. CWHM12 selectively inhibits αv integrins (IC₅₀s = 1.8, 0.8, 61, 1.5, and 0.2 nM for αvβ1, αvβ3, αvβ5, αvβ6, and αvβ8, respectively) over αIIbβ3, α2β1, and α10β1. CWHM 12 attenuates liver, lung, and pancreatic fibrosis in mice treated with CCl₄ or cerulein.

Uses

CWHM-12 is a potent inhibitor of αV integrins with IC50s of 0.2, 0.8, 1.5, and 1.8 nM for αvβ8, αvβ3, αvβ6, and αvβ1.

in vivo

Mice are treated with CCl₄ for 3 weeks to establish fibrotic disease and then treated with CWHM-12 (CWHM 12) or vehicle for the final 3 weeks of CCl₄. CWHM-12 significantly reduces liver fibrosis even after fibrotic disease have been established. Digital image quantitation demonstrates significantly reduced p-SMAD3 signaling in the livers of CWHM-12 treated mice compare to controls, demonstrating that the protection from CCl₄-induced hepatic fibrosis observed in CWHM-12 treated mice is due at least in part to a reduction in TGF-β activation by αv integrins. Besides, administration of CWHM-12 significantly inhibited progression of pulmonary fibrosis^[1].

References

[1] Henderson NC, et al. Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013 Dec;19(12):1617-24. DOI:10.1038/nm.3282
[2] Basta J, Robbins L, Stout L, Prinsen MJ, Griggs DW, Rauchman M. Pharmacologic inhibition of RGD-binding integrins ameliorates fibrosis and improves function following kidney injury. Physiol Rep. 2020;8(7):e14329. DOI:10.14814/phy2.14329

Preparation Products And Raw materials

(3S)-N-[3-Hydroxy-5-[(1,4,5,6-tetrahydro-5-hydroxy-2-pyriMidinyl)aMino] benzoyl]glycyl-3-(3-broMo-5-t-butylphenyl)-beta-alanine Supplier

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