Name: LP-533401
Brand: Adooq Bioscience
SKU: A14325
Availability: InStock
Rating: 5 (1 reviews)

Biological Activity

Bioactivity / Mechanism

LP-533401 inhibited purified human TPH1 competitively with tryptophan and predominantly uncompetitively with 6-methyltetrahydropterin. Reported Ki values were 0.31 ± 0.01 μM and 0.81 ± 0.03 μM, respectively (mean ± SEM; two independent experiments, each in triplicate). These substrate-dependent kinetic values do not establish isoform selectivity. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Cellular Effect

Cell Line	Activity	Value	Description	Reference
RBL-2H3	IC50	0.4 μM	Inhibition of TPH-1-mediated serotonin biosynthesis in rat RBL2H3 cells after 48 hrs by RP-HPLC analysis	[PMID: 24844139]

In Vitro Studies

Substrate-dependent inhibition of human TPH1

Biochemical assay · Purified recombinant full-length human TPH1 [1]

A single kinetic design varied tryptophan or 6-methyltetrahydropterin separately. LP-533401 was competitive with tryptophan and predominantly uncompetitive with the pterin cofactor. Ki values are assay parameters, not treatment doses or IC50 values.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Inhibition with tryptophan varied; 200 μM 6-MePH4 fixed	Ki, mean ± SEM 0.31 ± 0.01 μM	[1]
Inhibition with 6-MePH4 varied; 50 μM tryptophan fixed	Ki, mean ± SEM 0.81 ± 0.03 μM	[1]

Literature-Reported Treatment Conditions

Treatment concentration: Trp-variable series: 0, 0.25, 0.5 and 1.0 μM LP-533401; pterin-variable series: 0, 0.5, 1.0 and 2.0 μM.
Exposure duration: 5 min reaction at room temperature.
Method: Recombinant full-length human TPH1 assay; HPLC fluorescence measurement of 5-HTP. Zero-inhibitor conditions served as controls.
Reported limits: Solvent fraction for the kinetic assay is not specified in the read methods. The DMSO stock described for crystallization was not assigned to this assay.

Methods and source locations

Compound reported in the paper: LP-533401; Compound label in the paper: LP-533401

Compound-level biochemical evidence; does not establish A14325 lot performance, bulk salt equivalence, isoform selectivity or cellular potency.

Materials; Enzyme Kinetic Studies; Kinetic Analysis of Inhibition; Table 1; Figure 6A–B

Inhibition with tryptophan varied; 200 μM 6-MePH4 fixed: HPLC quantification of 5-HTP; nonlinear competitive-inhibition fit; two independent experiments, each in triplicate. — Table 1, LP-533401/Trp row and footnotes; Figure 6A; Enzyme Kinetic Studies

Inhibition with 6-MePH4 varied; 50 μM tryptophan fixed: HPLC quantification of 5-HTP; nonlinear uncompetitive-inhibition fit; two independent experiments, each in triplicate. — Table 1, LP-533401/6-MePH4 row and footnotes; Figure 6B; Enzyme Kinetic Studies

In Vivo Studies

In neonatal rats, LP533401 at 30 mg/kg by oral gavage every other day from postnatal day 4 reduced colonic serotonin at day 11. The same design showed reduced myenteron thickness and increased crypt depth, with no significant change in colon length (n = 6 per group). These short-term developmental findings limit assumptions of uniformly beneficial gastrointestinal effects; long-term consequences remain unknown. [2]

Colonic serotonin and morphology after early-life LP533401 exposure

Animal study · Sprague Dawley neonatal rat pups; 18 pups randomized to naïve, solvent-gavage or LP533401-gavage groups (n = 6 per group); endpoint postnatal day 11. [2]

One randomized exposure design reduced colonic 5-HT and was accompanied by lower myenteron thickness and greater crypt depth. Colon length did not differ significantly. TPH1 fluorescence showed a nonsignificant downward trend. These are neonatal short-term observations; lasting effects and generalization to adult animals were not established.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Colonic tissue 5-HT after LP533401 versus naïve and solvent controls	Direction and reported significance Lower; P < 0.01 versus each control group in Figure 1B.	[2]
Colonic myenteron thickness and crypt depth	Direction and reported significance Lower myenteron thickness and greater crypt depth versus both controls (P < 0.05).	[2]
Colon length	Reported significance No significant difference between groups; P > 0.05.	[2]
Colonic TPH1 immunofluorescence, LP versus solvent control	P value P = 0.06; downward trend, not statistically significant.	[2]

Study groups and reported outcomes
Group / dose	Comparator	Observed result	Reference
Naïve control	Untreated baseline group.	Comparator for colonic serotonin, morphology and colon length.	[2]
Solvent-gavage control Equal solvent volume	Naïve animals and LP-treated animals.	Gavage alone did not significantly change colonic 5-HT versus naïve animals.	[2]
LP533401 30 mg/kg	Solvent-gavage and naïve groups.	Lower colonic 5-HT, lower myenteron thickness, increased crypt depth; no significant colon-length difference; TPH1 fluorescence P = 0.06 versus solvent control.	[2]

Naïve control: Model: Neonatal Sprague Dawley rats; n = 6.; Reported limits: Sex and litter allocation not specified in the read experimental design.

Solvent-gavage control: Model: Neonatal Sprague Dawley rats; n = 6.; Route: Oral gavage; Frequency: Every other day at 08:00; Treatment course: Starting day 4; assessed day 11.; Vehicle: PEG200:5% dextrose solution, 40:60 (v/v).; Reported limits: Sex and litter allocation not specified in the read experimental design.

LP533401: Model: Neonatal Sprague Dawley rats; n = 6.; Route: Oral gavage; Frequency: Every other day at 08:00; Treatment course: Starting day 4; assessed day 11.; Vehicle: PEG200:5% dextrose solution, 40:60 (v/v).; Reported limits: Sex and litter allocation not specified in the read experimental design.

Methods and source locations

Compound reported in the paper: LP-533401; Compound label in the paper: LP group

Named-compound neonatal-rat observations. No Adooq product or lot equivalence, adult safety, therapeutic benefit or causal mechanism for morphology is inferred.

Experimental design; Measurement of 5-HT levels; Histology and immunofluorescence; Statistics and visualization; Figures 1–2

Colonic tissue 5-HT after LP533401 versus naïve and solvent controls: ELISA of colon tissue; n = 6 per group; figure data shown as mean ± SEM. — Results: LP533401 gavage altered host tryptophan–5-HT metabolism; Figure 1B and caption; Measurement of 5-HT levels

Colonic myenteron thickness and crypt depth: H&E histology and Image-Pro Plus measurement; n = 6 per group; mean ± SEM; one-way ANOVA with Fisher LSD. — Results: Inhibition of peripheral 5-HT affected colonic phenotype; Figure 2B–D and caption; Histology and immunofluorescence; Statistics

Colon length: Colon length comparison; n = 6 per group; mean ± SEM. — Results: Inhibition of peripheral 5-HT affected colonic phenotype; Figure 2A and caption

Colonic TPH1 immunofluorescence, LP versus solvent control: Quantified mean immunofluorescence intensity; n = 6 per group; mean ± SEM. — Figure 1D; Results: LP533401 gavage altered host tryptophan–5-HT metabolism

Naïve control · Experimental design; Figure 1A–D; Figure 2A–D

Solvent-gavage control · Experimental design; Figure 1A–D; Figure 2A–D

LP533401 · Experimental design; Figure 1A–D; Figure 2A–D

Specifications

Manufacturer	Adooq Bioscience
Actions	Inhibitor
CAS Number	945976-43-2
Applications	Tph1 inhibitor
Formula	C₂₇H₂₂F₄N₄O₃
Molecular Weight	526.5
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

Storage & Solubility

In Vitro Solubility

Reported Solubility

No reported solubility data are available for this product.

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

[1] Giovanni Cianchetta, Terry Stouch, Wangsheng Yu, et al. Mechanism of Inhibition of Novel Tryptophan Hydroxylase Inhibitors Revealed by Co-crystal Structures and Kinetic Analysis Current Chemical Genomics (2010). PMID: 20556201 DOI: 10.2174/1875397301004010019 Source material
[2] Yidan Ling, Ziyu Liu, Shuibing Han, et al. Integrated omics revealed the altered colonic microenvironment after inhibition of peripheral serotonin synthesis by LP533401 iMetaOmics (2024). PMID: 41676120 DOI: 10.1002/imo2.34 Source material

Publications

1 publication citing this product

Dongna Li, .et al. , Sci Rep, 2024, Aug 2;14(1):17951 PMID: 39095450

Documents & Downloads

LP-533401

Publications for LP-533401

Select a Size

Package Sizes

LP-533401 5 mg

Free Aliquoting for Your Order