LP533401 hcl Chemical Properties

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

solubility 

≥56.3 mg/mL in DMSO; insoluble in H2O; ≥19.4 mg/mL in EtOH

form 

solid

color 

Light yellow to yellow

LP533401 hcl Usage And Synthesis

Uses

LP-533401 hydrochloride is a tryptophan hydroxylase 1 inhibitor that regulates serotonin production in the gut.

Biological Activity

lp533401 hcl is an inhibitor of tph-1 [1].tryptophan hydroxylase-1 (tph-1) is an isoenzyme of tryptophan hydroxylase and the initial enzyme in gut- and lung-derived serotonin biosynthesis. tph-1 is mainly expressed in the gut and lung [2].lp533401 hcl is a tph-1 inhibitor. in rat rbl2h3 cells expressing tph1, lp533401 (1 μm) completely inhibited serotonin production. lp533401 reduced the activity of recombinant wild-type tph-1 by 70% by interacting with residues tyr235 and phe241 [1].in rodents, lp533401 orally administration was incapable of crossing the blood-brain barrier. in mice, lp533401 (250 mg/kg) dose-dependently reduced serum serotonin concentration by 30%. in ovariectomized female c57bl6/j mice, lp533401 (10, 100, 250 mg/kg for 28 days) increased bone mass and bone-formation parameters such as osteocalcin serum concentration, osteoblast numbers and bone formation rate. also, lp533401 dose-dependently decreased serum serotonin concentration but didn’t affect brain serotonin content. in ovariectomized female rats, lp533401 completely rescued the ovariectomy-induced osteopenia [1]. in transgenic sm22-5-htt+ mice overexpressing 5-ht transporter (5-htt) in smooth muscle cells and spontaneously developing pulmonary hypertension (ph), lp533401 (250 mg/kg for 21 days) significantly reduced lung and blood 5-ht levels, vascular ki67-positive cells, distal pulmonary artery muscularization, right ventricular (rv) hypertrophy and rv systolic pressure [2].

in vivo

References

[1]. yadav vk, balaji s, suresh ps, et al. pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. nat med, 2010, 16(3): 308-312.
[2]. abid s, houssaini a, chevarin c, et al. inhibition of gut- and lung-derived serotonin attenuates pulmonary hypertension in mice. am j physiol lung cell mol physiol, 2012, 303(6): l500-508.