[CAS NO. 1309357-15-0] Silmitasertibsodiumsalt
PRODUCTS SPECIFICATIONS [1309357-15-0]
DESCRIPTION [1309357-15-0]
Overview
| MDL | MFCD28385881 |
|---|---|
| Molecular Weight | 371.75 |
| Molecular Formula | C19H11ClN3NaO2 |
| SMILES | O=C(C1=CC=C2C3=C(C(NC4=CC=CC(Cl)=C4)=NC2=C1)C=CN=C3)O[Na] |
16 Publications Citing Use of MCE
- [1]Science. 2017 Dec 1;358(6367):eaan4368.
- [2]Nat Cell Biol. 2021 Mar;23(3):257-267.
- [3]Sci Transl Med. 2018 Jul 18;10(450):eaaq1093.
- [4]Nat Commun. 2023 Feb 9;14(1):731.
- [5]EMBO Mol Med. 2020 Aug 7;12(8):e11987.
- [6]Oncogene. 2022 Jan;41(4):571-585.
- [7]Oncogene. 2017 Aug 24;36(34):4943-4950.
- [8]Cancers (Basel). 2021, 13(5), 1127.
- [9]Int J Mol Sci. 2021 Jan 15;22(2):E819.
- [10]Int J Mol Sci. 2020 Mar 3;21(5):1718.
- [11]Cells. 2021 Jan 18;10(1):E181.
- [12]Invest Ophthalmol Vis Sci. 2022 Dec 1;63(13):14.
- [13]Oncol Rep. 2017 Feb;37(2):1141-1147.
- [14]Biochem Biophys Res Commun. 2020 Oct 20;531(3):409-415.
- [15]Patent. US20180263995A1.
- [16]Oncotarget. 2016 Aug 16;7(33):53191-53203.
Summary
Silmitasertib sodium salt is an orally bioavailable, highly selective and potent CK2 inhibitor, with IC 50 values of 1 nM against CK2α and CK2α'.
IC50 & Target
|
CK2α 1 nM (IC 50 ) |
CK2α' 1 nM (IC 50 ) |
In Vitro
Silmitasertib (CX-4945) causes cell-cycle arrest and selectively induces apoptosis in cancer cells relative to normal cells, attenuates PI3K/Akt signalingand, and the antiproliferative activity of Silmitasertib (CX-4945) is correlated with expression levels of the CK2α catalytic subunit, Attenuation of PI3K/Akt signaling [1] . Silmitasertib (CX-4945) with PS-341 treatment prevents leukemic cells from engaging a functional UPR in order to buffer the PS-341-mediated proteotoxic stress in ER lumen, and decreases pro-survival ER chaperon BIP/Grp78 expression [2] . Silmitasertib (CX-4945) induces cytotoxicity and apoptosis, and exerts anti-proliferative effects in hematological tumors by downregulating CK2 expression and suppressing activation of CK2-mediated PI3K/Akt/mTOR signaling pathways [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Silmitasertib (CX-4945) (25 or 75 mg/kg, p.o.) is well tolerated and demonstrated robust antitumor activity with concomitant reductions of the mechanism-based biomarker phospho-p21 (T145) in murine xenograft models [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT03904862 | Pediatric Brain Tumor Consortium|St. Jude Children´s Research Hospital|National Cancer Institute (NCI) |
Medulloblastoma, Childhood
|
March 18, 2019 | Phase 1|Phase 2 |
| NCT01199718 | Cylene Pharmaceuticals |
Multiple Myeloma
|
September 2010 | Phase 1 |
| NCT04668209 | University of Arizona|Senhwa Biosciences, Inc. |
Coronavirus
|
January 1, 2021 | Phase 2 |
| NCT04663737 | Chris Recknor, MD|Senhwa Biosciences, Inc. |
Covid19
|
December 3, 2020 | Phase 2 |
| NCT02128282 | Senhwa Biosciences, Inc. |
Cholangiocarcinoma
|
June 2014 | Phase 1|Phase 2 |
| NCT03897036 | Senhwa Biosciences, Inc. |
Carcinoma, Basal Cell
|
April 1, 2019 | Phase 1 |
| NCT00891280 | Cylene Pharmaceuticals |
Advanced Solid Tumors|Breast Cancer|Inflammatory Breast Cancer|Castleman´s Disease|Multiple Myeloma
|
February 2009 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
H 2 O : 16.67 mg/mL ( 44.84 mM ; Need ultrasonic)
DMSO : 6.67 mg/mL ( 17.94 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.6900 mL | 13.4499 mL | 26.8998 mL |
| 5 mM | 0.5380 mL | 2.6900 mL | 5.3800 mL |
| 10 mM | 0.2690 mL | 1.3450 mL | 2.6900 mL |
-
1.
Add each solvent one by one: PBS
Solubility: 25 mg/mL (67.25 mM); Clear solution; Need ultrasonic
-
2.
-
3.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.08 mg/mL (5.60 mM); Clear solution
-
4.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (5.60 mM); Clear solution
References
- [1] Siddiqui-Jain A, et al. CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy. Cancer Res. 2010 Dec 15;70(24):10288-98.
- [2] Kendall JJ, et al. CK2 blockade causes MPNST cell apoptosis and promotes degradation of β-catenin. Oncotarget. 2016 Aug 16;7(33):53191-53203.
- [3] Buontempo F, et al. Synergistic cytotoxic effects of PS-341 and CK2 inhibitor CX-4945 in acute lymphoblastic leukemia: turning off the prosurvival ER chaperone BIP/Grp78 and turning on the pro-apoptotic NF-κB. Oncotarget. 2016 Jan 12;7(2):1323-40.
- [4] Chon HJ, et al. The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies. Front Pharmacol. 2015 Mar 31;6:70.
