Synonym
GLPG-1690; GLPG 1690; GLPG1690; ziritaxestat.
IUPAC/Chemical Name
2-((2-ethyl-6-(4-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperazin-1-yl)-8-methylimidazo[1,2-a]pyridin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile
InChi Key
REQQVBGILUTQNN-UHFFFAOYSA-N
InChi Code
InChI=1S/C30H33FN8O2S/c1-4-24-29(35(3)30-34-27(25(14-32)42-30)20-5-7-21(31)8-6-20)39-15-22(13-19(2)28(39)33-24)37-11-9-36(10-12-37)18-26(41)38-16-23(40)17-38/h5-8,13,15,23,40H,4,9-12,16-18H2,1-3H3
SMILES Code
CCC(N=C1N2C=C(C=C1C)N3CCN(CC3)CC(N4CC(C4)O)=O)=C2N(C)C5=NC(C6=CC=C(C=C6)F)=C(S5)C#N
Appearance
White 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, not in water
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
Note: chemical structure of GLPG-1690 was from: https://newdrugapprovals.org/2016/03/ (visited 4/7/2016).
Biological target:
Ziritaxestat (GLPG1690) is a first-in-class autotaxin (ATX) inhibitor, with an IC50 of 131 nM.
In vitro activity:
To assess GLPG1690-induced cell signaling changes, this study screened 43 P-kinase sites and 2 related proteins in the LAM patient-derived TSC2-deficient cells and the TSC2 add-back control cells treated with GLPG1690 (6 μM, 6 hr) or DMSO. Twenty-four of these P-kinase sites (or proteins) showed greater than 25% suppression by GLPG1690 treatment specifically in the TSC2-deficient cells; 8 of them showed greater than 50% change with the inhibitor, including Erk1/2 (T202/Y204, T185/Y187) and Akt1/2/3 (S473) (Supplementary Figure 5A), which are known to mediate signaling downstream of LPAR/S1PR 28–34. This study confirmed the effect of GLPG1690 on Akt and Erk phosphorylation by immunoblotting: 6 hr-treatment with GLPG1690 (6 μM) led to a decrease in P-Akt (S473) by 68 ± 10% and in P-Erk (T202/Y204) by 56 ± 12% in the human TSC2-deficient cells (Figure 4A–B). P-S6 (S235/236), a direct target of mTORC1, was not affected under this condition. Consistent results were obtained in Tsc2−/− MEFs (Supplementary Figure 5B).
Reference: Cancer Res. 2020 Jul 1; 80(13): 2751–2763. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335343/
In vivo activity:
Chronic inflammation is widely recognized as one of the “hallmarks” of cancer, and inflammation is augmented by irradiation, which
may be associated with irradiation-induced fibrosis. Blocking ATX with GLPG1690 decreased the concentrations of CCL11, IL9,
IL12 p40, M-CSF, and IFNγ in tumors or tumor-adjacent adipose tissue of irradiated mice. Importantly, these proinflammatory
cytokines are closely related to the pathogenesis of pulmonary fibrosis. Activation of LPA1 receptors drives fibrosis in several fibrotic
conditions, and consequently, blocking LPA formation with GLPG1690 should theoretically attenuate the development of irradiationinduced fibrosis as it does in the case of idiopathic pulmonary fibrosis.
Reference: Mol Cancer Ther. 2020 Jan; 19(1): 63-74. https://mct.aacrjournals.org/content/19/1/63.long
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
70.8 |
120.32 |
| Ethanol |
4.0 |
6.79 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
588.71
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.
| 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. Feng Y, Mischler WJ, Gurung AC, Kavanagh TR, Androsov G, Sadow PM, Herbert ZT, Priolo C. Therapeutic Targeting of the
Secreted Lysophospholipase D Autotaxin Suppresses Tuberous Sclerosis Complex-Associated Tumorigenesis. Cancer Res. 2020 Jul
1;80(13):2751-2763. doi: 10.1158/0008-5472.CAN-19-2884. Epub 2020 May 11. PMID: 32393662; PMCID: PMC7335343.
2. Tang X, Wuest M, Benesch MGK, Dufour J, Zhao Y, Curtis JM, Monjardet A, Heckmann B, Murray D, Wuest F, Brindley DN.
Inhibition of Autotaxin with GLPG1690 Increases the Efficacy of Radiotherapy and Chemotherapy in a Mouse Model of Breast
Cancer. Mol Cancer Ther. 2020 Jan;19(1):63-74. doi: 10.1158/1535-7163.MCT-19-0386. Epub 2019 Sep 23. PMID: 31548293.
In vitro protocol:
Feng Y, Mischler WJ, Gurung AC, Kavanagh TR, Androsov G, Sadow PM, Herbert ZT, Priolo C. Therapeutic Targeting of the
Secreted Lysophospholipase D Autotaxin Suppresses Tuberous Sclerosis Complex-Associated Tumorigenesis. Cancer Res. 2020 Jul
1;80(13):2751-2763. doi: 10.1158/0008-5472.CAN-19-2884. Epub 2020 May 11. PMID: 32393662; PMCID: PMC7335343.
In vivo protocol:
Tang X, Wuest M, Benesch MGK, Dufour J, Zhao Y, Curtis JM, Monjardet A, Heckmann B, Murray D, Wuest F, Brindley DN.
Inhibition of Autotaxin with GLPG1690 Increases the Efficacy of Radiotherapy and Chemotherapy in a Mouse Model of Breast
Cancer. Mol Cancer Ther. 2020 Jan;19(1):63-74. doi: 10.1158/1535-7163.MCT-19-0386. Epub 2019 Sep 23. PMID: 31548293.
1: Desroy N, Housseman C, Bock X, Joncour A, Bienvenu N, Cherel L, Labeguere V, Rondet E, Peixoto C, Grassot JM, Picolet O, Annoot D, Triballeau N, Monjardet A, Wakselman E, Roncoroni V, Le Tallec S, Blanque R, Cottereaux C, Vandervoort N, Christophe T, Mollat P, Lamers M, Auberval M, Hrvacic B, Ralic J, Oste L, van der Aar E, Brys R, Heckmann B. Discovery of 2-[[2-Ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1-yl]-8-methyli midazo[1,2-a]pyridin-3-yl]methylamino]-4-(4-fluorophenyl)thiazole-5-carbonitrile (GLPG1690), a First-in-Class Autotaxin Inhibitor Undergoing Clinical Evaluation for the Treatment of Idiopathic Pulmonary Fibrosis. J Med Chem. 2017 May 1. doi: 10.1021/acs.jmedchem.7b00032. [Epub ahead of print] PubMed PMID: 28414242.
