WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205842
CAS#: 1320346-97-1
Description: GLPG0187 is a small molecule integrin receptor antagonist (IRA) with potential antineoplastic activity. Upon administration, GLPG0187 binds to and blocks the activity of 5 RGD-integrin receptor subtypes, including alphavbeta1, alphavbeta3, alphavbeta5, alphavbeta6 and alpha5beta1. This may result in the inhibition of endothelial cell-cell interactions and endothelial cell-matrix interactions, and the prevention of angiogenesis and metastasis in tumor cells expressing these integrin receptors. Integrin receptors are transmembrane glycoproteins expressed on the surface of tumor vessel endothelial cells and some types of cancer cells, and play a crucial role in endothelial cell adhesion and migration.
MedKoo Cat#: 205842
Name: GLPG0187
CAS#: 1320346-97-1
Chemical Formula: C29H37N7O5S
Exact Mass: 595.2577
Molecular Weight: 595.719
Elemental Analysis: C, 58.47; H, 6.26; N, 16.46; O, 13.43; S, 5.38
Synonym: GLPG0187; GLPG 0187; GLPG-0187
IUPAC/Chemical Name: (S)-3-((2,5-dimethyl-6-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)piperidin-1-yl)pyrimidin-4-yl)amino)-2-((4-methoxyphenyl)sulfonamido)propanoic acid.
InChi Key: CXHCNOMGODVIKB-VWLOTQADSA-N
InChi Code: InChI=1S/C29H37N7O5S/c1-18-26(31-17-25(29(37)38)35-42(39,40)23-9-7-22(41-3)8-10-23)32-19(2)33-28(18)36-15-12-20(13-16-36)24-11-6-21-5-4-14-30-27(21)34-24/h6-11,20,25,35H,4-5,12-17H2,1-3H3,(H,30,34)(H,37,38)(H,31,32,33)/t25-/m0/s1
SMILES Code: O=C(O)[C@H](CNC1=NC(C)=NC(N2CCC(C3=NC4=C(CCCN4)C=C3)CC2)=C1C)NS(=O)(C5=CC=C(OC)C=C5)=O
Appearance: Solid powder
Purity: >98%
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: >5 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
| Biological target: | GLPG0187 is a broad spectrum integrin receptor antagonist with antitumor activity; inhibits αvβ1-integrin with an IC50 of 1.3 nM. |
| In vitro activity: | In this study, Cell viability, proliferation and migration in vitro were also quantified following treatment with GLPG0187. Cell viability was not affected by GLPG0187 at varying concentrations over 72 hr (Fig. 3a, data shown for 50 ng/ml only). However, GLPG0187 treatment resulted in cell rounding and clumping, in contrast vehicle-control treated cells were adherent and elongated in shape. GLPG0187 demonstrated a dose-dependent significant reduction (p < 0.05) in tumour cell migration compared to control after 16 hr (Fig. 3b), with 50 ng/ml stimulating the maximal response (p < 0.005). GLPG0187 at all concentrations significantly reduced cell proliferation compared to vehicle control at 24 (p < 0.05), 48, 72 and 96 hr (p < 0.005; Fig. 3c). Reference: Int J Cancer. 2015 Apr 1;136(7):1731-40. https://pubmed.ncbi.nlm.nih.gov/25156971/ |
| In vivo activity: | A single murine metatarsal was engrafted into a dorsal skinfold chamber implanted on a SCID mouse. Fluorescently-labeled human prostate (PC3-GFP) or oral (SCC4-GFP) cancer cells were administered via intracardiac (i.c) injection, with simultaneous daily GLPG0187 or vehicle-control treatment (i.p. 100 mg/kg/day) for the experimental duration. The metatarsal-DSC model was then used to investigate any modulation of PC3-GFP cells homing to bone, in the presence of the αν integrin antagonist. GLPG0187 significantly (p < 0.05) reduced the number of tumour cells present in the implanted metatarsal from day 17 onward (Fig. 3d). Tumour cell numbers remained significantly lower (p < 0.05) in treatment groups compared to controls throughout the duration of the experiment. Whole body imaging of the mouse during the experimental period did not detect tumour cells in either treated or control groups, in the skeleton or organs. However, at post mortem following removal of the muscle from the bone, small tumours were visible in the tibia of control animals but this did not occur in GLPG0187-treated mice. Reference: Int J Cancer. 2015 Apr 1;136(7):1731-40. https://pubmed.ncbi.nlm.nih.gov/25156971/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 8.0 | 13.43 |
The following data is based on the product molecular weight 595.719 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. Reeves KJ, Hurrell JE, Cecchini M, van der Pluijm G, Down JM, Eaton CL, Hamdy F, Clement-Lacroix P, Brown NJ. Prostate cancer cells home to bone using a novel in vivo model: modulation by the integrin antagonist GLPG0187. Int J Cancer. 2015 Apr 1;136(7):1731-40. doi: 10.1002/ijc.29165. Epub 2014 Sep 4. PMID: 25156971. 2. van der Horst G, van den Hoogen C, Buijs JT, Cheung H, Bloys H, Pelger RC, Lorenzon G, Heckmann B, Feyen J, Pujuguet P, Blanque R, Clément-Lacroix P, van der Pluijm G. Targeting of α(v)-integrins in stem/progenitor cells and supportive microenvironment impairs bone metastasis in human prostate cancer 3. Li Y, Drabsch Y, Pujuguet P, Ren J, van Laar T, Zhang L, van Dam H, Clément-Lacroix P, Ten Dijke P. Genetic depletion and pharmacological targeting of αv integrin in breast cancer cells impairs metastasis in zebrafish and mouse xenograft models. Breast Cancer Res. 2015 Feb 25;17(1):28. doi: 10.1186/s13058-015-0537-8. PMID: 25849225; PMCID: PMC4381510. |
| In vitro protocol: | 1. Reeves KJ, Hurrell JE, Cecchini M, van der Pluijm G, Down JM, Eaton CL, Hamdy F, Clement-Lacroix P, Brown NJ. Prostate cancer cells home to bone using a novel in vivo model: modulation by the integrin antagonist GLPG0187. Int J Cancer. 2015 Apr 1;136(7):1731-40. doi: 10.1002/ijc.29165. Epub 2014 Sep 4. PMID: 25156971. 2. van der Horst G, van den Hoogen C, Buijs JT, Cheung H, Bloys H, Pelger RC, Lorenzon G, Heckmann B, Feyen J, Pujuguet P, Blanque R, Clément-Lacroix P, van der Pluijm G. Targeting of α(v)-integrins in stem/progenitor cells and supportive microenvironment impairs bone metastasis in human prostate cancer |
| In vivo protocol: | 1.Li Y, Drabsch Y, Pujuguet P, Ren J, van Laar T, Zhang L, van Dam H, Clément-Lacroix P, Ten Dijke P. Genetic depletion and pharmacological targeting of αv integrin in breast cancer cells impairs metastasis in zebrafish and mouse xenograft models. Breast Cancer Res. 2015 Feb 25;17(1):28. doi: 10.1186/s13058-015-0537-8. PMID: 25849225; PMCID: PMC4381510. 2. Reeves KJ, Hurrell JE, Cecchini M, van der Pluijm G, Down JM, Eaton CL, Hamdy F, Clement-Lacroix P, Brown NJ. Prostate cancer cells home to bone using a novel in vivo model: modulation by the integrin antagonist GLPG0187. Int J Cancer. 2015 Apr 1;136(7):1731-40. doi: 10.1002/ijc.29165. Epub 2014 Sep 4. PMID: 25156971. |
1: van der Horst G, van den Hoogen C, Buijs JT, Cheung H, Bloys H, Pelger RC, Lorenzon G, Heckmann B, Feyen J, Pujuguet P, Blanque R, Clément-Lacroix P, van der Pluijm G. Targeting of α(v)-integrins in stem/progenitor cells and supportive microenvironment impairs bone metastasis in human prostate cancer. Neoplasia. 2011 Jun;13(6):516-25. PubMed PMID: 21677875; PubMed Central PMCID: PMC3114245.
GalapagosÂ’ candidate drug, GLPG0187, is an integrin receptor antagonist (IRA) that binds to six integrin receptors known to be present in many metastatic cancers, affording a unique anti-integrin profile. In animal studies, oral administration of GLPG0187 as a single agent has been shown to inhibit multiple processes involved in the spread and growth of metastatic tumors. GLPG0187 therefore offers a new approach to treat metastases, a severe complication of many cancers. In the first-in-human trial, GLPG0187 showed good safety and a promising biomarker profile in healthy volunteers. Based on these results, Galapagos initiated a Phase Ib study in March 2011. In this Phase Ib study, Galapagos plans to assess the safety and explore the preliminary efficacy of GLPG0187 in cancer patients. (source: http://www.glpg.com/index.php/randd/pipeline/glpg0187-cancer/).
