EST64454 HCl
new
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 555898

CAS#: 1950569-11-5 (HCl)

Description: EST64454 is a Highly Soluble σ1 Receptor Antagonist Clinical Candidate for Pain Management. EST64454 shows an outstanding aqueous solubility, which together with its high permeability in Caco-2 cells will allow its classification as a BCS class I compound. It also shows high metabolic stability in all species, linked to an adequate pharmacokinetic profile in rodents, and antinociceptive properties in the capsaicin and partial sciatic nerve ligation models in mice.


Chemical Structure

img
EST64454 HCl
CAS# 1950569-11-5 (HCl)

Theoretical Analysis

MedKoo Cat#: 555898
Name: EST64454 HCl
CAS#: 1950569-11-5 (HCl)
Chemical Formula: C18H23ClF2N4O2
Exact Mass: 0.00
Molecular Weight: 400.855
Elemental Analysis: C, 53.93; H, 5.78; Cl, 8.84; F, 9.48; N, 13.98; O, 7.98

Price and Availability

Size Price Availability Quantity
5mg USD 125 Ready to ship
10mg USD 210 Ready to ship
25mg USD 450 Ready to ship
50mg USD 750 Ready to ship
100mg USD 1250 Ready to ship
200mg USD 1950 Ready to ship
500mg USD 2950 Ready to ship
1g USD 3950 Ready to ship
Bulk inquiry

Related CAS #: 1351438-26-0 (free base)   1950569-11-5 (HCl)    

Synonym: EST64454 HCl; EST64454 hydrochloride; EST64454; EST-64454; EST 64454;

IUPAC/Chemical Name: 1-(4-(2-((1-(3,4-difluorophenyl)-1H-pyrazol-3-yl)methoxy)ethyl)piperazin-1-yl)ethan-1-one hydrochloride

InChi Key: YJZGDOPAALDWAT-UHFFFAOYSA-N

InChi Code: InChI=1S/C18H22F2N4O2.ClH/c1-14(25)23-8-6-22(7-9-23)10-11-26-13-15-4-5-24(21-15)16-2-3-17(19)18(20)12-16;/h2-5,12H,6-11,13H2,1H3;1H

SMILES Code: CC(N1CCN(CCOCC2=NN(C3=CC=C(F)C(F)=C3)C=C2)CC1)=O.[H]Cl

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: >2 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).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: EST64454 hydrochloride is a selective and orally active sigma-1 receptor antagonist with a Ki of 22 nM.
In vitro activity: EST64454 is a selective sigma-1 receptor ligand intended for orally administered pain treatment that showed a promising profile in the lead optimization process. As part of the preliminary compound profiling, the potential for future drug-drug interactions was explored in vitro. Both direct and time-dependent CYP inhibition for CYP1A2, 2C9, 2C19, 2D6 and 3A4 was studied in human liver microsomes. EST64454 showed a low potential for CYP inhibition (IC50 between 100 and 1000 µM) and as time-dependent inhibitor (IC50 shift mainly around 1). CYP induction studies with HepaRG™ cells revealed no CYP induction at concentrations ≤50 µM, as shown by the CYP1A2, 3A4 and 2B6 activities measured. EST64454 was not a P-glycoprotein (P-gp) substrate and was highly permeable in Caco-2 cells. Reference: Biol Pharm Bull. 2020;43(1):68-76. https://pubmed.ncbi.nlm.nih.gov/31902934/
In vivo activity: The compound 9k (EST64454) showed in vivo efficacy after oral administration in two different pain models in mice: intraplantar capsaicin-induced mechanical hypersensitivity and partial sciatic nerve ligation (PSNL)-induced mechanical hypersensitivity, a model representative of neuropathic pain. In the capsaicin test, the antiallodynic potency of 9k was similar to that of the compound 1 (ED50 33 vs 28 mg/kg, respectively, Figure 3, Table 2). In the PSNL model, oral administration of 9k at 80 mg/kg, revealed an increased antiallodynic efficacy when comparing with the same dose of the compound 1 (95% vs 54%, respectively). Reference: J Med Chem. 2020 Dec 10;63(23):14979-14988. https://pubmed.ncbi.nlm.nih.gov/31902934/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 249.47

Preparing Stock Solutions

The following data is based on the product molecular weight 400.85 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Díaz JL, García M, Torrens A, Caamaño AM, Enjo J, Sicre C, Lorente A, Port A, Montero A, Yeste S, Álvarez I, Martín M, Maldonado R, de la Puente B, Vidal-Torres A, Cendán CM, Vela JM, Almansa C. EST64454: a Highly Soluble σ1 Receptor Antagonist Clinical Candidate for Pain Management. J Med Chem. 2020 Dec 10;63(23):14979-14988. doi: 10.1021/acs.jmedchem.0c01575. Epub 2020 Nov 25. PMID: 33237785. 2. Yeste S, Reinoso RF, Ayet E, Pretel MJ, Balada A, Serafini MT. Preliminary in Vitro Assessment of the Potential of EST64454, a Sigma-1 Receptor Antagonist, for Pharmacokinetic Drug-Drug Interactions. Biol Pharm Bull. 2020;43(1):68-76. doi: 10.1248/bpb.b19-00542. PMID: 31902934.
In vitro protocol: 1. Yeste S, Reinoso RF, Ayet E, Pretel MJ, Balada A, Serafini MT. Preliminary in Vitro Assessment of the Potential of EST64454, a Sigma-1 Receptor Antagonist, for Pharmacokinetic Drug-Drug Interactions. Biol Pharm Bull. 2020;43(1):68-76. doi: 10.1248/bpb.b19-00542. PMID: 31902934.
In vivo protocol: 1. Díaz JL, García M, Torrens A, Caamaño AM, Enjo J, Sicre C, Lorente A, Port A, Montero A, Yeste S, Álvarez I, Martín M, Maldonado R, de la Puente B, Vidal-Torres A, Cendán CM, Vela JM, Almansa C. EST64454: a Highly Soluble σ1 Receptor Antagonist Clinical Candidate for Pain Management. J Med Chem. 2020 Dec 10;63(23):14979-14988. doi: 10.1021/acs.jmedchem.0c01575. Epub 2020 Nov 25. PMID: 33237785.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Díaz JL, García M, Torrens A, Caamaño AM, Enjo J, Sicre C, Lorente A, Port A, Montero A, Yeste S, Álvarez I, Martín M, Maldonado R, de laPuente B, Vidal- Torres A, Cendán CM, Vela JM, Almansa C. EST64454: a Highly Soluble σ1 Receptor Antagonist Clinical Candidate for Pain Management. J Med Chem. 2020 Dec 10;63(23):14979-14988. doi: 10.1021/acs.jmedchem.0c01575. Epub 2020 Nov 25. PMID: 33237785.


2: Yeste S, Reinoso RF, Ayet E, Pretel MJ, Balada A, Serafini MT. Preliminary in Vitro Assessment of the Potential of EST64454, a Sigma-1 Receptor Antagonist, for Pharmacokinetic Drug-Drug Interactions. Biol Pharm Bull. 2020;43(1):68-76. doi: 10.1248/bpb.b19-00542. PMID: 31902934.