ACHP Hydrochloride - ≥99% , CAS No.406209-26-5

CAS: 406209-26-5 Cat. No.: A648736 Molecular Weight: 400.90 PubChem CID: 136216943

GRADE & PURITY ≥99%

Storage

Store at 2-8°C

Shipped In

Wet ice

Overview

ACHP Hydrochloride (IKK-2 Inhibitor VIII) is a highly potent and selective IKK-β inhibitor with an IC 50 of 8.5 nM.

In Vitro

ACHP Hydrochloride (Compound 4j) exhibits potent IKK-β inhibitory (IC 50 : 8.5 nM) and cellular activities (IC 50 =40 nM, in A549 cells). ACHP moderately inhibits IKK-α with an IC 50 of 250 nM but exhibits good selectivity towards other kinases, such as IKK3, Syk and MKK4 (IC 50 >20,000 nM). Moreover, ACHP demonstrates quite potent activity in various cellular assays. ACHP inhibits NF-κB-dependent reporter gene activation in TNFα-activated HEK293 cells and PMA/calcium ionophore-activated Jurkat T cells. ACHP fails to inhibit PMA-induced AP-1 activation in MRC-5 cells and PMA/calcium ionophore induced NF-κB dependent reporter gene transcription in Jurkat cells even at concentrations exceeding 10 μM. ACHP selectively interferes with the NF-κB signaling cascade by inhibition of IKK-β in living cells. ACHP inhibits the growth of these cells in a dose-dependent manner. Tax-active cell lines are more susceptible to ACHP than Tax-inactive cell lines and Jurkat (IC 50 values in Tax-active cell lines, Tax-inactive cell lines or Jurkat are 3.1±1.3 μM, 10.7±1.7 μM and 23.6 μM, respectively), suggesting that the growth of Tax-active cells depends on NF-κB more than Tax-inactive cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

ACHP (Compound 4j) is orally bioavailable in mice and rats and demonstrates significant in vivo activity in anti-inflammatory models (arachidonic acid-induced mouse ear edema model). ACHP has reasonable aqueous solubility (0.12 mg/mL in pH 7.4 isotonic buffer) and excellent Caco-2 permeability (P app 62.3×10 -7 cm/s), and demonstrates orally bioavailability in mice (BA: 16%) and rats (BA: 60%). The favourable bioavailability of ACHP in rats is likely due to its low clearance (0.33 L/h/kg). In an acute inflammation model, ACHP exhibits oral efficacy at 1 mg/kg in a dose-dependent manner . MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay

HTLV-1-infected T-cell lines, ATL-35T, 81-66/45, MJ, and MT-2 cells, human ATL cell lines established from ATL patients, ATL-102, ED-40515(−) and TL-Om1 cells, and a HTLV-1-negative T-cell leukemia cell line Jurkat are used in this study. Approximately 1.5×10 4 cells are cultured in 96-well plate in triplicates at 37°C. Growth inhibitory effect of ACHP (0.01, 0.1, 1, 5, 10, 50 and 100 μM) is determined using MTT assay. Optical densities (OD) at 570 and 630 nm are measured with multiplate reader. Cell viability (%) is calculated. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Form:Solid

IC50& Target:IKK-β 8.5 nM (IC 50 ) IKK-α 250 nM (IC 50 )

Specifications

Specifications & Purity

≥99%

Biochemical and Physiological Mechanisms

ACHP Hydrochloride (IKK-2 Inhibitor VIII) is a highly potent and selective IKK-β inhibitor with an IC 50 of 8.5 nM.

Storage

Store at 2-8°C

Shipped In

Wet ice

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Purity

≥99%

Names and Identifiers

• Isomeric SMILES: C1CC1COC2=CC=CC(=C2C3=NC(=C(C(=C3)C4CCNCC4)C#N)N)O.Cl
• PubChem CID: 136216943
• Molecular Weight: 400.90

Chemical and Physical Properties

• Solubility: DMSO : 50 mg/mL (124.72 mM; Need ultrasonic) H2O : <0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)
• Molecular Weight: 400.900 g/mol
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 400.167 Da
• Monoisotopic Mass: 400.167 Da
• Topological Polar Surface Area: 104.000 Ų
• Heavy Atom Count: 28
• Formal Charge: 0
• Complexity: 540.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 2

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