LP533401 hcl

LP533401 hcl Property

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

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

LP533401 hcl Chemical Properties,Usage,Production

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.