TP0463518
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MedKoo CAT#: 555388

CAS#: 1558021-37-0

Description: TP0463518 is a novel, highly potent HIF prolyl hydroxylase (PHD) inhibitor. TP0463518 competitively inhibited human PHD2 with a Ki value of 5.3 nM. TP0463518 also inhibited human PHD1/3 with IC50 values of 18 and 63 nM as well as monkey PHD2 with an IC50 value of 22 nM. In normal mice and rats, TP0463518 significantly increased the serum EPO levels at doses of 5 and 20 mg/kg, respectively.


Price and Availability

Size
Price

500mg
USD 2450
Size
Price

1g
USD 3450
Size
Price

2g
USD 5850

TP0463518, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

No image available

Theoretical Analysis

MedKoo Cat#: 555388
Name: TP0463518
CAS#: 1558021-37-0
Chemical Formula: C20H18ClN3O6
Exact Mass: 431.0884
Molecular Weight: 431.829
Elemental Analysis: C, 55.63; H, 4.20; Cl, 8.21; N, 9.73; O, 22.23


Synonym: TP0463518; TP-0463518; TP 0463518;

IUPAC/Chemical Name: (1-((6-(4-chlorophenoxy)pyridin-3-yl)methyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine

InChi Key: HMMHKGLPKAQOOH-UHFFFAOYSA-N

InChi Code: InChI=1S/C20H18ClN3O6/c21-13-2-4-14(5-3-13)30-16-6-1-12(9-22-16)11-24-8-7-15(25)18(20(24)29)19(28)23-10-17(26)27/h1-6,9,25H,7-8,10-11H2,(H,23,28)(H,26,27)

SMILES Code: O=C(O)CNC(C1=C(O)CCN(CC2=CC=C(OC3=CC=C(Cl)C=C3)N=C2)C1=O)=O


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO

Shelf Life:
>3 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
2934990300


Additional Information

The correlation factors for serum EPO and the serum TP0463518 levels were 0.95 in mice and 0.92 in rats. TP0463518 also increased the serum EPO level in 5/6 nephrectomized chronic kidney disease model rats at a dose of 10 mg/kg, with a correlation factor for serum EPO and the serum TP0463518 levels of 0.82. Finally, the effect of TP0463518 in monkeys was investigated. TP0463518 was promptly removed with a half-life of 5.2 h and increased the area under the curve (AUC) of EPO at a dose of 5 mg/kg. The EPO and TP0463518 levels were also correlated. P0463518 induces endogenous EPO with a strong pharmacokinetic-pharmacodynamic correlation and may contribute to desirable hemoglobin control in patients with renal anemia.


References

1: Kato S, Takayama N, Takano H, Koretsune H, Koizumi C, Kunioka EI, Uchida S,
Takahashi T, Yamamoto K. TP0463518, a novel inhibitor for hypoxia-inducible
factor prolyl hydroxylases, increases erythropoietin in rodents and monkeys with
a good pharmacokinetics-pharmacodynamics correlation. Eur J Pharmacol. 2018 Nov
5;838:138-144. doi: 10.1016/j.ejphar.2018.08.044. Epub 2018 Sep 1. PubMed PMID:
30179610.

2: Shinfuku A, Shimazaki T, Fujiwara M, Sato F, Watase H, Numazaki T, Kawakita Y,
Mutoh M, Yamasaki H, Takayama N, Kato S, Sugimoto T, Maruyama J. Novel Compound
Induces Erythropoietin Secretion through Liver Effects in Chronic Kidney Disease
Patients and Healthy Volunteers. Am J Nephrol. 2018;48(3):157-164. doi:
10.1159/000492181. Epub 2018 Sep 3. PubMed PMID: 30176654; PubMed Central PMCID:
PMC6214603.