[CAS NO. 1056901-62-2] AT13148
PRODUCTS SPECIFICATIONS [1056901-62-2]
DESCRIPTION [1056901-62-2]
Overview
| MDL | MFCD25976789 |
|---|---|
| Molecular Weight | 313.78 |
| Molecular Formula | C17H16ClN3O |
| SMILES | ClC1=CC=C([C@](C2=CC=C(C3=CNN=C3)C=C2)(O)CN)C=C1 |
2 Publications Citing Use of MCE
Summary
IC50 & Target
|
Akt1 38 nM (IC 50 ) |
p70S6K 8 nM (IC 50 ) |
Akt3 50 nM (IC 50 ) |
Akt2 402 nM (IC 50 ) |
PKA 3 nM (IC 50 ) |
ROCKII 4 nM (IC 50 ) |
ROCKI 6 nM (IC 50 ) |
|||
|
SGK3 63 nM (IC 50 ) |
RSK1 85 nM (IC 50 ) |
CHK2 860 nM (IC 50 ) |
Aurora B 1840 nM (IC 50 ) |
||||||
In Vitro
AT13148 inhibits a panel of kinases at 10 μM, and the IC 50 values for p70S6K, PKA, ROCKI, and ROCKII are all less than 10 nM and those for AKT1, 2, and 3 are 38, 402, and 50 nM, respectively. For the related AGC kinases RSK1 and SGK3, the IC 50 values are 85 and 63 nM, respectively. In contrast, IC 50 values for the non-AGC kinases CHK2 and Aurora B are both greater than 800 nM. AT13148 potently inhibits proliferation with GI 50 values of 1.5 to 3.8 μM across a selected panel of cancer cell lines [1] . AT13148 treatment in gastric cancer cells dramatically suppresses activation of multiple AGC kinases, including Akt (at p-Thr-308), p70S6 kinase (p70S6K), glycogen synthase kinase 3β (GSK-3β) and p90 ribosomal S6 kinase (RSK) [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Oral drug administration of 5 mg/kg of AT13148 results in complete bioavailability. Clear inhibition of phosphorylation of the AKT substrates GSK3β, tuberin, and the p70S6K target S6RP are also observed in PTEN-deficient MES-SA human uterine tumor xenografts after treatment with 40 and 50 mg/kg p.o. of AT13148 [1] . Oral gavage of AT13148 at well-tolerated doses significantly inhibits HGC27 xenograft tumor growth in nude mice. AGC activity is also dramatically decreased in AT13148-administrated HGC27 tumors [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT01585701 | Cancer Research UK |
Advanced Solid Tumours
|
May 2012 | Phase 1 |
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 : 50 mg/mL ( 159.35 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.1869 mL | 15.9347 mL | 31.8695 mL |
| 5 mM | 0.6374 mL | 3.1869 mL | 6.3739 mL |
| 10 mM | 0.3187 mL | 1.5935 mL | 3.1869 mL |
References
- [1] Yap TA, et al. AT13148 is a novel, oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumor activity. Clin Cancer Res. 2012 Jul 15;18(14):3912-23.
- [2] Xi Y, et al. AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo. Biochem Biophys Res Commun. 2016 Sep 9;478(1):330-6