PXS-5153A monohydrochloride

• CAT Number: I046046
• Molecular Formula: C20H24ClFN4O2S
• Molecular Weight: 438.95
• Purity: ≥95%
• Synonyms: 3-[1-[(Z)-4-amino-2-fluorobut-2-enyl]-2-methylpyrrolo[3,2-b]pyridin-3-yl]-N,N-dimethylbenzenesulfonamide;hydrochloride
• InChI: InChI=1S/C20H23FN4O2S.ClH/c1-14-19(15-6-4-7-17(12-15)28(26,27)24(2)3)20-18(8-5-11-23-20)25(14)13-16(21)9-10-22;/h4-9,11-12H,10,13,22H2,1-3H3;1H/b16-9-
• InChIKey: KLWZKAGUIGUVAY-LFMIJCLESA-N
• SMILES: CC1=C(C2=C(N1CC(=CCN)F)C=CC=N2)C3=CC(=CC=C3)S(=O)(=O)N(C)C.Cl

PXS-5153A monohydrochloride is a potent, selective, orally active and fast-acting lysyl oxidase like 2/3 enzymatic (LOXL2/LOXL3) inhibitor, with an IC50 of <40 nM for LOXL2 across all mammalian species and an IC50 of 63 nM for human LOXL3. PXS-5153A monohydrochloride could reduce crosslinks and ameliorates fibrosis.
PXS-5153A exhibits an IC50 of <40 nM for LOXL2 across all mammalian species tested. PXS-5153A also inhibits human LOXL3 with an IC50 value of 63 nM. PXS-5153A is >40-fold selective for LOXL2 over both LOX and LOXL1 and >700-fold selective over other related amine oxidases. PXS-5153A is a fast acting inhibitor, with enzymatic activity almost entirely blocked within 15 minutes [1].
As expected, rhLOXL2 dose-dependently induce oxidation of collagen with PXS-5153A dose-dependently impeding collagen oxidation. Therapeutic treatment of PXS-5153A substantially reduces immature crosslink formation compared with the CCl4 treated animals. Mature crosslink formation is also reduced by PXS-5153A treatment. All groups with therapeutic treatment of PXS-5153A show a significant reduction in DHLNL formation compared to the CCl4 treated animals. Treatment with PXS-5153A causes a significantly reduction in HYP compared to the CCl4 group. In addition, the amount of fibrillar collagen is markedly augmented by disease as seen by the 2.2-fold increase in percentage coverage area by Picrosirius red staining, which is reduced by PXS-5153A[1].

Reference

[1]. Schilter H, et al. The lysyl oxidase like 2/3 enzymatic inhibitor, PXS-5153A, reduces crosslinks and ameliorates fibrosis. J Cell Mol Med. 2018 Dec 9.
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