Ziritaxestat
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MedKoo CAT#: 522696

CAS#: 1628260-79-6

Description: Ziritaxestat, also known as GLPG1690, is a selective autotaxin inhibitor discovered by Galapagos, with potential application in idiopathic pulmonary disease (IPF). In a Phase 1 study in healthy human volunteers, GLPG1690 demonstrated favorable safety and tolerability, as well as a strong pharmacodynamic signal implying target engagement.

Chemical Structure

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Ziritaxestat
CAS# 1628260-79-6
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 522696
Name: Ziritaxestat
CAS#: 1628260-79-6
Chemical Formula: C30H33FN8O2S
Exact Mass: 588.24
Molecular Weight: 588.710
Elemental Analysis: C, 61.21; H, 5.65; F, 3.23; N, 19.03; O, 5.44; S, 5.45

Price and Availability

Size Price Availability Quantity
10mg USD 110 Ready to ship
25mg USD 220 Ready to ship
50mg USD 380 Ready to ship
100mg USD 650 Ready to ship
200mg USD 1050 Ready to ship
500mg USD 2250 Ready to ship
1g USD 3950 Ready to ship
2g USD 6650 Ready to ship
Bulk inquiry

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

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 70.8 120.32
Ethanol 4.0 6.79

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.

Recalculate based on batch purity %
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.

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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.