Cat. No.: HY-146662

HPGDS inhibitor 3

HPGDS inhibitor 3 is an orally active and highly potent peripherally restricted hematopoietic prostaglandin D synthase (H-PGDS) inhibitor with IC₅₀ value of 9.4 nM and EC₅₀ of 42 nM, respectively. HPGDS inhibitor 3 exhibits good selectivity, good pharmacokinetic parameters in mouse, rat, and dog, and no CNS toxicity. HPGDS inhibitor 3 has anti-inflammatory activity.

For research use only. We do not sell to patients.

CAS No.: 2255311-93-2
Formula: C₂₁H₂₇N₃O₂
Molecular Weight:353.46

Storage:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (278 KB)

HPGDS inhibitor 3 Chemical Structure

CAS No.: 2255311-93-2

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vivo
Chemical Information
Protocols (5)
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

IC₅₀: 9.4 nM (H-PGDS)^[1]
EC₅₀: 42 nM (H-PGDS)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
Mast cell	EC₅₀	3.4 nM Compound: 1y	Anti-inflammatory activity against mast cell degranulation inflammatory C57BL/6J mouse model assessed as blood EC50 required for reduction in compound 48/80-induced PGD2 release into peritoneal lavage fluid administered orally with compound and 1 hr later Anti-inflammatory activity against mast cell degranulation inflammatory C57BL/6J mouse model assessed as blood EC50 required for reduction in compound 48/80-induced PGD2 release into peritoneal lavage fluid administered orally with compound and 1 hr later	[PMID: 33059303]
Mast cell	ED₅₀	0.009 mg/kg Compound: 1y	Anti-inflammatory activity against mast cell degranulation inflammatory C57BL/6J mouse model assessed as reduction in compound 48/80-induced PGD2 release into peritoneal lavage fluid administered orally with compound and 1 hr later treated with compound 4 Anti-inflammatory activity against mast cell degranulation inflammatory C57BL/6J mouse model assessed as reduction in compound 48/80-induced PGD2 release into peritoneal lavage fluid administered orally with compound and 1 hr later treated with compound 4	[PMID: 33059303]

In Vivo

HPGDS inhibitor 3 (compound 1y) (1-3 mg/kg; PO and IV; single) has a lower IV clearance, similar steady state volume of distribution, longer terminal half-life, and high oral bioavailability, as well as very low brain exposures in mouse, rat and dog^[1].
HPGDS inhibitor 3 (0.003-1 mg/kg; PO; single) attenuates PGD₂ release to baseline levels in a dose-dependent manner; also inhibits LPS-induced PGD₂ increase in plasma and skeletal muscle in a dose-dependent manner^[1].
HPGDS inhibitor 3 (0.003-1 mg/kg; PO; single) ^[1].
HPGDS inhibitor 3 (1, 3, and 10 mg/kg; PO; q.d., for 16 days) significantly enhances functional recovery of injured limbs, and hastens the time to full functional recovery of injured limb muscles^[1].
HPGDS inhibitor 3 (10, 30 and 100 mg/kg; PO; once daily, for 7 days or 4 days) exhibits well tolerated at 30 mg/kg/day in rat but not tolerated at 100 mg/kg/day; shows well tolerated at 30 mg/kg/day in dogs but not tolerated at 75 mg/kg/day^[1].
Pharmacokinetic Parameters of HPGDS inhibitor 3 in mice, rats and dogs^[1].

	Mouse IV, 1 mg/kg PO, 3 mg/kg	Rat IV, 0.4 mg/kg PO, 2.4 mg/kg	Dog IV, 0.5 mg/kg PO, 1 mg/kg
T_1/2 (h)	2.9	5.1	6.2
CL (mL/min/kg)	9.0	4.5	1.9
V_ss (L/kg)	1.6	1.6	1.0
F (%)	71	100	92
Brain:blood ratio	0.06

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Male C57BL/6J mice (murine mast cell degranulation model of inflammation)^[1]
Dosage:

0.003, 0.01, 0.03, 0.1, 0.3 and 1.0 mg/kg
Administration:

PO; single (anesthetized 1 hour later, intraperitoneally injected with 0.2 mL PBS or 48/80 (0.75 mg/mL))
Result:

Attenuated PGD₂ release to baseline levels in a dose-dependent manner with an ED₅₀ of 0.009 mg/kg (blood EC₅₀ = 3.4 nM) in this acute inflammation model.

Animal Model:

Male C57BL6/N mice (12 weeks, n=6)^[1]
Dosage:

0.003, 0.01, 0.03, 0.1, 0.3 and 1.0 mg/kg
Administration:

PO; single (intraperitoneally injection of PBS or 20 ng/kg LPS 1 hour later)
Result:

Inhibited LPS-induced PGD2 increase in plasma and skeletal muscle in a dose-dependent manner.

Animal Model:

Male C57Bl/6 mice (10-12 weeks, n=7-8; chronic eccentric contraction-induced muscle injury models)^[1]
Dosage:

1, 3, and 10 mg/kg
Administration:

PO; q.d., for 16 days
Result:

Significantly enhanced functional recovery of injured limbs, and significantly hastened the time to full functional recovery of injured limb muscles, with maximal efficacy observed at ≥ 10 mg/kg q.d..

Animal Model:

Mdx mouse (6-8 mouths, duchenne muscular dystrophy model)^[1]
Dosage:

0.1, 0.3, 1, 3, and 10 mg/kg
Administration:

PO; q.d., for 43 days
Result:

Significantly improved functional recovery (~90% to 100% restoration), following eccentric contraction-induced muscle injury in mdx mice.

Animal Model:

Male Wistar Han rat and dog^[1]
Dosage:

10, 30 and 100 mg/kg for rat; 10, 30, and 75 mg/kg for dog
Administration:

PO; once daily; for 7 days (rat) or for 4 days (dog)
Result:

In rat, the AUC values at 10, 30, and 100 mg/kg/day were 120, 410, and 820 µg•hr/mL, respectively; respective C_max values were 8.7, 24, and 57 μg/mL. In dog, it showed well tolerated at dose levels up to 30 mg/kg/day with no abnormal microscopic findings; but exhibited discoloration in the small intestine and esophagus (female) at 75 mg/kg/day.

Animal Model:

Mice, rats, dongs^[1]
Dosage:

1 mg/kg IV and 3 mg/kg p.o in mice, 0.4 mg/kg IV and 2.4 mg/kg PO in rat, 0.5 mg/kg IV and 1 mg/kg PO in dog
Administration:

IV and PO; single (Pharmacokinetics Analysis)
Result:

Had a lower IV clearance, similar steady state volume of distribution, longer terminal half-life, and high oral bioavailability, as well as very low brain exposures in mouse, rat and dog.

Chemical Information

CAS No. 2255311-93-2
Molecular Weight 353.46
Formula C₂₁H₂₇N₃O₂
SMILES

CC(O)([C@H]1CC[C@@H](CC1)NC(C2=CC3=CC=C(N=C3N=C2)C4CC4)=O)C
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Protocols

All Animals and Diseases Cell Biology Signal Pathway Related

Neurotoxicity Study
This protocol assesses in vitro neurotoxicity by combining neuronal viability, mitochondrial/metabolic activity, neurite outgrowth, and optional neuronal network function readouts. Calcein-AM or resazurin/PrestoBlue readouts estimate viable or metabolically active cells; βIII-tubulin immunofluorescence detects neuronal morphology and neurite networks; TMRE detects mitochondrial membrane potential; and MEA recordings detect functional changes in neuronal network activity.
Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
Cotton Pellet Granuloma
Cotton pellet granuloma is a classical in vivo chronic inflammation model used to evaluate the anti-inflammatory potential of test substances by measuring their ability to inhibit granuloma tissue formation around an implanted foreign body (cotton pellet) in rodents. The method is based on the biological response to a sterile implanted material, which induces proliferative phase inflammation characterized by fibroblast proliferation and collagen-rich granuloma formation, and the final readout reflects the extent of chronic inflammatory tissue growth surrounding the pellet. In multiple preclinical pharmacological evaluations, inhibition of cotton pellet-induced granuloma formation has been used as an indicator of anti-inflammatory activity in both synthetic and natural product screening contexts.
Carrageenan-Induced Paw Edema
Carrageenan-induced paw edema is an acute inflammation model in which intraplantar injection of carrageenan induces localized inflammatory swelling characterized by vascular permeability, leukocyte infiltration, and production of inflammatory mediators such as prostaglandins and cytokines, making it widely used to evaluate anti-inflammatory agents in vivo. The resulting paw volume or thickness increase is quantified over time as a direct readout of inflammatory intensity and drug efficacy, typically reflecting cyclooxygenase-mediated prostaglandin-driven edema formation and immune cell recruitment in peripheral tissue[20].
Research Protocol for Inflammation-related Diseases
The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (278 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Cadilla R, Deaton DN, Do Y, et al. The exploration of aza-quinolines as hematopoietic prostaglandin D synthase (H-PGDS) inhibitors with low brain exposure. Bioorg Med Chem. 2020;28(23):115791. [Content Brief]

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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HPGDS inhibitor 3