LP533401 (LP-533401) is a novel and potent inhibitor of tryptophan hydroxylase 1 with the potential for the treatment for osteoporosis. It is able tp regulate serotonin production in the gut.

Physicochemical Properties

Molecular Formula	C27H22F4N4O3
Molecular Weight	526.4916
Exact Mass	526.162
CAS #	945976-43-2
Related CAS #	LP-533401 hydrochloride;1040526-12-2
PubChem CID	44560455
Appearance	Brown to breen solid powder
Density	1.4±0.1 g/cm3
Boiling Point	699.0±65.0 °C at 760 mmHg
Flash Point	376.5±34.3 °C
Vapour Pressure	0.0±2.3 mmHg at 25°C
Index of Refraction	1.609
LogP	5.62
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	8
Heavy Atom Count	38
Complexity	759
Defined Atom Stereocenter Count	1
SMILES	C1=CC(=CC(=C1)F)C2=CC=C(C=C2)C(C(F)(F)F)OC3=NC(=NC(=C3)C4=CC=C(C=C4)C[C@@H](C(=O)O)N)N
InChi Key	JZWUKILTKYJLCN-XEGCMXMBSA-N
InChi Code	InChI=1S/C27H22F4N4O3/c28-20-3-1-2-19(13-20)16-8-10-18(11-9-16)24(27(29,30)31)38-23-14-22(34-26(33)35-23)17-6-4-15(5-7-17)12-21(32)25(36)37/h1-11,13-14,21,24H,12,32H2,(H,36,37)(H2,33,34,35)/t21-,24?/m0/s1
Chemical Name	(2S)-2-amino-3-[4-[2-amino-6-[2,2,2-trifluoro-1-[4-(3-fluorophenyl)phenyl]ethoxy]pyrimidin-4-yl]phenyl]propanoic acid
Synonyms	LP-533401 LP 533401 LP533401
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	At a dosage of 1 μM, LP-533401 totally suppresses the synthesis of serotonin in Tph1-expressing cells (RBL2H3 cells)[1].
ln Vivo	Due to a distinct increase in bone production, oral administration of this small molecule once daily for up to 6 weeks completely rescues and prevents the onset of osteoporosis in ovariectomized rodents in a dose-dependent way. After oral treatment, LP-533401 levels in the brain are insignificant, according to pharmacokinetic tests conducted on mice, suggesting that it is essentially unable to penetrate the blood-brain barrier[1]. Repeated administration of LP-533401 (30–250 mg/kg per day) to mice results in significant decreases in 5-HT levels in the blood, lungs, and stomach but not in the brain. Lung and gut 5-HT contents drop by 50% following a single LP533401 dose (250 mg/kg), while blood 5-HT levels stay constant, indicating gut and lung 5-HT synthesis[2]. When administered with the Tph-1 inhibitor LP-533401, adult, healthy mice exhibit a 30% drop in serotonin levels in the blood, which is followed by a 30% increase in osteoblast counts. Giving LP533401 to mice that have received an EL4 cell injection prevents the loss in trabecular bone volume and osteoblast counts, prolongs survival, and lowers leukemic infiltration[3].
References	[1]. Inhibition of gut-derived serotonin synthesis: A potential bone anabolic treatment. Nat. Med. 16(3), 308-312 (2010). [2]. Inhibition of gut- and lung-derived serotonin attenuates pulmonary hypertension in mice. Am J Physiol Lung Cell Mol Physiol. 2012 Sep 15;303(6):L500-8. [3]. Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts. Blood. 2014 Oct 30;124(18):2834-46.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8994 mL	9.4969 mL	18.9937 mL
	5 mM	0.3799 mL	1.8994 mL	3.7987 mL
	10 mM	0.1899 mL	0.9497 mL	1.8994 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.