Home Cytoskeletal Signaling Integrin inhibitor Cilengitide trifluoroacetate

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Cilengitide trifluoroacetate Integrin inhibitor

Cat.No.S7077

Cilengitide (EMD 121974, NSC 707544) is a potent integrin inhibitor for αvβ3 receptor and αvβ5 receptor with IC50 of 4.1 nM and 79 nM in cell-free assays, respectively; ~10-fold selectivity against gpIIbIIIa. Phase 2.
Cilengitide trifluoroacetate Integrin inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 702.68

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Quality Control

Batch: Purity: 99.50%
99.50

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
G28 Function Assay 50 μg/ml 30/60/120 min inhibits phosphorylation of FAK, Src and Akt 19114005
HMEC-1  Function Assay 20/40/60 μg/ml inhibits FAK and Src  19114005
G44 Apoptosis Assay 1/5/50 μg/ml 24 h induces apoptosis 19114005
G28 Apoptosis Assay 1/5/50 μg/ml 24 h induces apoptosis 19114005
G44 Proliferation Assay 1/5/50 μg/ml 24/48/72 h inhibits proliferation in a dose dependent manner 19114005
G28 Proliferation Assay 1/5/50 μg/ml 24/48/72 h inhibits proliferation in a dose dependent manner 19114005
HMEC-1  Apoptosis Assay 1/5/50 μg/ml 24 h induces apoptosis 19114005
HMEC-1  Proliferation Assay 1/5/50 μg/ml 24/48/72 h inhibits proliferation in a dose dependent manner 19114005
HMEC-1  Function Assay 1/5/50 μg/ml 24 h induces a dose dependent detachment  19114005
LNT-229  Function Assay 0.1/1/10 μM 24 h impairs the adhesion of cells to vitronectin in a dose dependent manner 19221171
T98G Function Assay 0.1/1/10 μM 24 h impairs the adhesion of cells to vitronectin in a dose dependent manner 19221171
LN-18 Function Assay 0.1/1/10 μM 24 h impairs the adhesion of cells to vitronectin in a dose dependent manner 19221171
LN-308 Function Assay 0.1/1/10 μM 24 h impairs the adhesion of cells to vitronectin in a dose dependent manner 19221171
U87MG Function Assay 0.1/1/10 μM 24 h impairs the adhesion of cells to vitronectin in a dose dependent manner 19221171
U87  Function Assay 0-25 μg/mL 12 h  induces autophagy dose dependently 21788343
U251 Function Assay 0-25 μg/mL 12 h  induces autophagy dose dependently 21788343
U87  Apoptosis Assay 25 μg/mL 24/48 h induces apoptosis at 48 h significantly 21788343
U251 Apoptosis Assay 25 μg/mL 24/48 h induces apoptosis at 48 h significantly 21788343
U87  Growth Inhibition Assay 0-25 μg/mL 0-48 h inhibits cell growth in dose and time dependent manner 21788343
U251 Growth Inhibition Assay 0-25 μg/mL 0-48 h inhibits cell growth in dose and time dependent manner 21788343
U251MG Apoptosis Assay 1 µM 48 h induces apoptosis 23354807
U87MG Apoptosis Assay 1 µM 48 h induces apoptosis 23354807
U251MG Growth Inhibition Assay 0-25 μM 24/48 h inhibits cell growth in dose and time dependent manner 23354807
U87MG Growth Inhibition Assay 0-25 μM 24/48 h inhibits cell growth in dose and time dependent manner 23354807
MCF-7  Apoptosis Assay 0-20 μM 48 h induces apoptosis 24153102
T-47D Apoptosis Assay 0-20 μM 48 h induces apoptosis 24153102
MCF-7  Growth Inhibition Assay 0-20 μM 96 h inhibits cell growth in a dose dependent manner 24153102
T-47D Growth Inhibition Assay 0-20 μM 96 h inhibits cell growth in a dose dependent manner 24153102
FaDu  Apoptosis Assay 25 µM  48 h  induces apoptosis 24557056
CAL27 Apoptosis Assay 25 µM  48 h  induces apoptosis 24557056
SCC25 Apoptosis Assay 25 µM  48 h  induces apoptosis 24557056
FaDu  Growth Inhibition Assay 6.25–200 µM 72 h results moderate, dose-dependent growth inhibition 24557056
CAL27 Growth Inhibition Assay 6.25–200 µM 72 h results moderate, dose-dependent growth inhibition 24557056
SCC25 Growth Inhibition Assay 6.25–200 µM 72 h results moderate, dose-dependent growth inhibition 24557056
H28 Cell Viability Assay 1 nM-200 μM 72 h decreases cell viability in a dose dependent manner 24595274
MM05 Cell Viability Assay 1 nM-200 μM 72 h decreases cell viability in a dose dependent manner 24595274
MSTO-211H Cell Viability Assay 1 nM-200 μM 72 h decreases cell viability in a dose dependent manner 24595274
REN Cell Viability Assay 1 nM-200 μM 72 h decreases cell viability in a dose dependent manner 24595274
LN-308  Function Assay 10 μm 24 h DMSO  reduces AhR protein levels and DRE reporter activity 26500056
HaCaT  Function Assay 10 μm 48 h DMSO  reduces TGF-β2 mRNA expression 26500056
S-24 Function Assay 1/10 μm 24 h DMSO  reduces DRE reporter activity 26500056
ZH-161 Function Assay 1/10 μm 24 h DMSO  reduces DRE reporter activity 26500056
LN-308  Function Assay 1/10/100 μm 24 h DMSO  reduces DRE reporter activity in a concentration-dependent manner 26500056
M21 Function assay 1 hr Binding affinity to integrin alphav/beta3 heterodimer in human M21 cells assessed as inhibition of integrin-mediated human M21 cell adhesion to vitronectin after 1 hr in presence of MnCl2, IC50 = 0.0004 μM. 26753814
HEK293T Function assay 2 hrs Binding affinity to soluble truncated human recombinant Fc-tagged alphaVbeta3 and integrins were expressed in HEK293T cells after 2 hrs by competition ELISA-like assay, IC50 = 0.00051 μM. 24095096
HT-29 Function assay 2 hrs Antagonist activity at integrin alphaVbeta5 (unknown origin) expressed in HT-29 cells assessed as reduction in cell adhesion to vitronectin after 2 hrs by MTT assay, IC50 = 0.12 μM. 28351594
HEK293 Function assay 2 hrs Antagonist activity at integrin alphaVbeta3 (unknown origin) expressed in HEK293 cells assessed as reduction in cell adhesion to fibrinogen after 2 hrs by MTT assay, IC50 = 0.22 μM. 28351594
SKOV3 Function assay 2 hrs Antagonist activity at integrin alphaVbeta3alphaVbeta5 (unknown origin) expressed in SKOV3 cells assessed as reduction in cell adhesion to fibrinogen after 2 hrs by MTT assay, IC50 = 0.37 μM. 28351594
U87MG Function assay 100 nM 24 hrs Inhibition of alphaVbeta3 integrin in human U87MG cells assessed as increase in p53 accumulation at 100 nM after 24 hrs by Western blot method 29775303
U87MG Function assay 100 nM 24 hrs Inhibition of alphaVbeta3 integrin in human U87MG cells assessed as increase in p53 accumulation at 100 nM after 24 hrs in presence of MDM2 inhibitor nutlin-3 by Western blot method 29775303
U87MG Function assay 100 nM 24 hrs Inhibition of alphaVbeta3 integrin in human U87MG cells assessed as increase in p53 accumulation at 100 nM after 24 hrs in presence of MDM2 inhibitor nutlin-3 and MDM4 inhibitor SJ-1722550 by Western blot method 29775303
U87MG Function assay 100 nM 8 hrs Inhibition of alphaVbeta3 integrin in human U87MG cells assessed as increase in MDM2 mRNA expression at 100 nM after 8 hrs in presence of MDM2 inhibitor nutlin-3 and MDM4 inhibitor SJ-1722550 by RT-PCR method 29775303
U87MG Function assay 100 nM 24 hrs Inhibition of alphaVbeta3 integrin in human U87MG cells assessed as increase in PUMA mRNA expression at 100 nM after 24 hrs by RT-PCR method 29775303
U87MG Function assay 100 nM 24 hrs Inhibition of alphaVbeta3 integrin in human U87MG cells assessed as increase in PUMA mRNA expression at 100 nM after 24 hrs in presence of MDM2 inhibitor nutlin-3 by RT-PCR method 29775303
U87MG Function assay 100 nM 24 hrs Inhibition of alphaVbeta3 integrin in human U87MG cells assessed as increase in PUMA mRNA expression at 100 nM after 24 hrs in presence of MDM4 inhibitor SJ-1722550 by RT-PCR method 29775303
U87MG Function assay 100 nM 24 hrs Inhibition of alphaVbeta3 integrin in human U87MG cells assessed as increase in PUMA mRNA expression at 100 nM after 24 hrs in presence of MDM2 inhibitor nutlin-3 and MDM4 inhibitor SJ-1722550 by RT-PCR method 29775303
U87MG Function assay 100 nM 24 hrs Inhibition of alphaVbeta3 integrin in human U87MG cells assessed as increase in p21 mRNA expression at 100 nM after 24 hrs by RT-PCR method 29775303
U87MG Antiproliferative assay 100 nM 72 hrs Antiproliferative activity against human U87MG cells at 100 nM after 72 hrs in presence of MDM2 inhibitor nutlin-3 by MTS assay 29775303
U87MG Antiproliferative assay 100 nM 72 hrs Antiproliferative activity against human U87MG cells at 100 nM after 72 hrs in presence of MDM2 inhibitor nutlin-3 and MDM4 inhibitor SJ-1722550 by MTS assay 29775303
U87MG Cell cycle assay 100 nM 24 hrs Cell cycle arrest in human U87MG cells assessed as accumulation at G0/G1 phase at 100 nM after 24 hrs 29775303
U87MG Anti-invasive assay 10 uM 24 hrs Anti-invasive activity in human U87MG cells at 10 uM after 24 hrs by transwell assay 29775303
U87MG Anti-invasive assay 10 uM 24 hrs Anti-invasive activity in human U87MG cells at 10 uM after 24 hrs in presence of MDM2 inhibitor nutlin-3 and MDM4 inhibitor SJ-1722550 by transwell assay 29775303
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight 702.68 Formula

C29H41F3N8O9

 Storage (From the date of receipt)
CAS No. 199807-35-7 Download SDF Storage of Stock Solutions

Synonyms EMD 121974, NSC 707544 Smiles CC(C)C1C(=O)NC(C(=O)NCC(=O)NC(C(=O)NC(C(=O)N1C)CC2=CC=CC=C2)CC(=O)O)CCCN=C(N)N.C(=O)(C(F)(F)F)O

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (142.31 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : 6.25 mg/mL

Ethanol : Insoluble

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Mass Concentration Volume Molecular Weight
Dilution Calculator Molecular Weight Calculator

In vivo
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Mechanism of Action

Targets/IC50/Ki
αvβ3 receptor
(Cell-free assay)
4.1 nM
αvβ5 receptor
(Cell-free assay)
79 nM
In vitro
Cilengitide is a cyclized pentapeptide peptidomimetic designed to compete for the arginine-glycine-aspartic acid (RGD) peptide sequence that regulates integrin-ligand binding. Cilengitide selectively and potently blocks the ligation of the αvβ3 and αvβ5 integrins to provisional matrix proteins such as vitronectin, fibronectin, fibrinogen, von Willebrand factor, osteopontin, and others. Cilegitide inhibits angiogenesis in vitro. 10 μM Cilengitide completely inhibits attachment of BAE, BME and HUVE cells on vitronectin and fibronectin. Cilengitide inhibits in vitro angiogenesis of BAE cells on three-dimensional collagen and fibrin gels pretreated with FGF-2(or VEGF-A) with IC50 of 15 μM and 8 μM, 4 μM and 3 μM, respectively. Cilengitide blocks proliferation and induces apoptosis of endothelial cells as well as differentiation of human endothelial precursor cells (EPCs). 50 μg/mL Cilengitide completely inhibits the proliferation of human microvascular endothelial cell line HMEC-1 and leads to apoptosis in ~30% cells. 1.0 μM Cilengitide treating for 9 days inhibits the proliferation of EPCs by nearly 40%. 1 μM Cilengitide inhibits the differentiation of EPCs by more than 80% at 14 days. Cilengitide inhibits adhesion and induces apoptosis of tumour cells. 25 μg/mL Cilengitide causes detachment of DAOY cells (medulloblastoma) and U87MG cells (glioblastoma) from vitronectin and tenascin by more than 60%. 25 μg/mL Cilengitide induces a nearly 50% apoptosis rate of these cells.
Kinase Assay
Integrin-binding competition assay
Recombinant soluble Integrins are immobilised, and peptides, which are serially diluted in Tris-buffered saline (TBS++) (0.1% (w/v) BSA, 150 mM NaCl, 1 mM CaCl2, 1 mM MgCl2 10 μM MnCl2, 20 mM Tris-HCl; pH 7.4), are added in parallel with biotinylated vitronectin (to 1μg/mL). After a 3-h incubation at 37℃ and washing with Tris–buffered saline, bound ligand is detected by incubation with an antibiotin alkaline phosphatase-conjugated antibody (BioRad) followed by development with p-nitrophenyl phosphatase substrate. The reaction is stopped by the addition of NaOH and the colour intensity read at 405 nm.
In vivo
Cilengitide is active against tumour growth and angiogenesis as a single-agent. 100 μg Cilengitide induces a significant decrease in the number of CD31+ vessels seen in tumours (2/high-power field) compared with control tumours (56/high-power field). 100 μg Cilengitide increases cellular apoptosis in the brain tumours of animals (2.2% apoptotic cells/high-power field) compared with those receiving the inactive peptide (1.7% cells/high-power field). Cilengitide treatment results in prolonged survival of the mice bearing melanoma xenografts M21 compared with control treatment group. (36.5 vs 17.3 days). Cilengitide can augment the therapeutic benefit associated with cytotoxic agents including chemotherapy and radiation therapy in tumour models. Cilengitide (250 mg/dose) alone does not alter tumour growth of breast cancer xenografts when compared with untreated mice, but combined modality RIT (CMRIT) using RIT and six doses of Cilengitide (250 mg/dose) increases efficacy of treatment, with the cure rate for mice that receives only RIT increasing from 15 to 53%. CMRIT significantly increases apoptosis of tumour and endothelial cells 5 days, and decreases tumour proliferation.
References
  • [4] https://pubmed.ncbi.nlm.nih.gov/17466276/
  • [5] https://pubmed.ncbi.nlm.nih.gov/11920637/
  • [6] https://pubmed.ncbi.nlm.nih.gov/12154028/

Applications

Methods Biomarkers Images PMID
Western blot GLI1 pFAK / p-AKT
S7077-WB2
31366904
Immunofluorescence VE-cadherin / β3 integrin
S7077-IF1
19212436
Growth inhibition assay Cell number
S7077-viability1
24153102

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01517776 Terminated
Gliomas
Martin-Luther-Universität Halle-Wittenberg|Merck KGaA Darmstadt Germany
 January 2012 Phase 2
NCT01118676 Completed
Locally Advanced Non Small Cell Lung Cancer (NSCLC)
Institut Claudius Regaud|Merck KGaA Darmstadt Germany
 March 2010 Phase 1

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Frequently Asked Questions

Question 1:
The recommended vehicle for it is 30% propylene glycol, 5% Tween 80, 65% D5W at 30mg/ml. Can you let me know if this is a suspension or clear solution?

Answer:
S7077 can be dissolved in 30% propylene glycol/5% Tween 80/65% D5W at 10 mg/ml as a clear solution.

Question 2:
Is it a TFA salt?

Answer:
S7077 is actually a TFA salt, and the ratio between it and TFA is 1:1.