[CAS NO. 303162-79-0] TAK-715
PRODUCTS SPECIFICATIONS [303162-79-0]
DESCRIPTION [303162-79-0]
Overview
| MDL | MFCD17012805 |
|---|---|
| Molecular Weight | 399.51 |
| Molecular Formula | C24H21N3OS |
| SMILES | O=C(C1=CC=CC=C1)NC2=NC=CC(C3=C(N=C(S3)CC)C4=CC=CC(C)=C4)=C2 |
9 Publications Citing Use of MCE
- [1]Sci Transl Med. 2018 Jul 18;10(450):eaaq1093.
- [2]J Invest Dermatol. 2019 Jan;139(1):224-234.
- [3]FASEB J. 2020 Nov;34(11):14892-14904.
- [4]Front Pharmacol. 2018 Jun 21;9:660.
- [5]Sci Rep. 2022 Sep 2;12(1):15001.
- [6]Poultry Sci. 2021, 101085.
- [7]Research Square Print. September 15th, 2022.
- [8]bioRxiv. July 24, 2021.
- [9]Harvard Medical School LINCS LIBRARY
Summary
IC50 & Target
|
p38α 7.1 nM (IC 50 ) |
p38β 200 nM (IC 50 ) |
p38δ >10 μM (IC 50 ) |
p38γ >10 μM (IC 50 ) |
CK1δ
|
CK1ε
|
In Vitro
TAK-715 (compound 8h) inhibits LPS-stimulated release of TNF-α from THP-1 (IC
50
=48 nM) and has no inhibitory activity for major CYPs, including CYP3A4. TAK-715 has no inhibition to p38γ/δ, JNK1, ERK1, IKKβ, MEKK1 or TAK1 (IC
50
>10 μM of all)
[1]
.
TAK 715 (10 μM; 1 hour) inhibits Wnt-3a-induced hDvl2 phosphorylation and the hDvl2 shift in U2OS-EFC cells
[2]
.
TAK-715 (1 μM; pretreatment for 16 hours) dramatically suppresses Norepinephrine (NE)-stimulated induction of fibronectin, CTGF, and Snai1 expression in TGF-β1-treated HK-2 cells at both the mRNA and protein levels
[3]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
TAK-715 (compound 8h; 3-30 mg/kg; PO) significantly reduces the secondary paw volume
[1]
.
TAK-715 (10 mg/kg; PO) has a C
max
of 0.19 μg/mL and an AUC of 1.16 μg•h/mL.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | 7-week-old male Lewis rats with arthritis [1] |
| Dosage: | 3, 10, 30 mg/kg |
| Administration: | PO; single dose |
| Result: | Significantly reduced the secondary paw volume (25% inhibition) |
| Animal Model: | Rat [1] |
| Dosage: | 10 mg/kg (Pharmacokinetic Analysis) |
| Administration: | PO |
| Result: | Had a C max of 0.19 μg/mL and an AUC of 1.16 μg•h/mL. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00760864 | Takeda |
Arthritis, Rheumatoid
|
August 2004 | Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 100 mg/mL ( 250.31 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.5031 mL | 12.5153 mL | 25.0307 mL |
| 5 mM | 0.5006 mL | 2.5031 mL | 5.0061 mL |
| 10 mM | 0.2503 mL | 1.2515 mL | 2.5031 mL |
-
1.
-
2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (6.26 mM); Clear solution
References
- [1] Miwatashi S, et al. Novel inhibitor of p38 MAP kinase as an anti-TNF-alpha drug: discovery of N-[4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (TAK-715) as a potent and orally active anti-rheumatoid arthritis agent. J Med Chem, 2005, 48(19), 5966-5979.
- [2] Verkaar F, et al. Inhibition of Wnt/β-catenin signaling by p38 MAP kinase inhibitors is explained by cross-reactivity with casein kinase Iδ/ɛ. Chem Biol, 2011, 18(4), 485-494.
- [3] Huiwen Ren, et al. Inhibition of α1-adrenoceptor reduces TGF-β1-induced epithelial-to-mesenchymal transition and attenuates UUO-induced renal fibrosis in mice. FASEB J. 2020 Nov;34(11):14892-14904.