Cilengitide TFA salt
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MedKoo CAT#: 200780A

CAS#: 199807-35-7 (TFA)

Description: Cilengitide is a cyclic Arg-Gly-Asp peptide with potential antineoplastic activity. Cilengitide binds to and inhibits the activities of the alpha(v)beta(3) and alpha(v)beta(5) integrins, thereby inhibiting endothelial cell-cell interactions, endothelial cell-matrix interactions, and angiogenesis.


Chemical Structure

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Cilengitide TFA salt
CAS# 199807-35-7 (TFA)

Theoretical Analysis

MedKoo Cat#: 200780A
Name: Cilengitide TFA salt
CAS#: 199807-35-7 (TFA)
Chemical Formula: C27H40N8O7
Exact Mass:
Molecular Weight: 702.7
Elemental Analysis: C, 55.09; H, 6.85; N, 19.04; O, 19.03

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50.0mg USD 250.0 Same day
100.0mg USD 450.0 Same day
200.0mg USD 850.0 Same day
500.0mg USD 1850.0 Same day
1.0g USD 2850.0 Same day
2.0g USD 4750.0 Same day
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Related CAS #: 199807-35-7 (TFA)   188968-51-6 (free base)   188969-00-8 (HCl)  

Synonym: EMD-85189; EMD 85189; EMD85189; EMD-121974; EMD121974; EMD 121974; NSC-707544; D03497; Cilengitide TFA salt; Cyclo(L-arginylglycyl-L-aspartyl-D-phenylalanyl-N-methyl-L-valyl)

IUPAC/Chemical Name: 2-((2S,5R,8S,11S)-5-benzyl-11-(3-((diaminomethylene)amino)propyl)-8-isopropyl-7-methyl-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaazacyclopentadecan-2-yl)acetic acid trifluroacetic acid

InChi Key: WHJCSACXAPYNTG-LOPTWHKWSA-N

InChi Code: InChI=1S/C27H40N8O7.C2HF3O2/c1-15(2)22-25(41)33-17(10-7-11-30-27(28)29)23(39)31-14-20(36)32-18(13-21(37)38)24(40)34-19(26(42)35(22)3)12-16-8-5-4-6-9-16;3-2(4,5)1(6)7/h4-6,8-9,15,17-19,22H,7,10-14H2,1-3H3,(H,31,39)(H,32,36)(H,33,41)(H,34,40)(H,37,38)(H4,28,29,30);(H,6,7)/t17-,18-,19+,22-;/m0./s1

SMILES Code: O=C(O)C[C@@H](C(N[C@H](CC1=CC=CC=C1)C(N(C)[C@@H](C(C)C)C(N[C@@H](CCC/N=C(N)\N)C(NC2)=O)=O)=O)=O)NC2=O.O=C(O)C(F)(F)F

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 water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in water

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: Cilengitide is an integrin inhibitor for αvβ3 and αvβ5 receptor, with IC50 values of 4 nM and 79 nM, respectively.
In vitro activity: Cilengitide inhibited adhesion of M14C2/MK18 cells to vitronectin in a dose-dependent manner, with an EC50 of 6.66 ± 1.77 µg/ml (Fig. 2a), whereas this agent did not affect adhesion to fibronectin (used as negative control since it mainly interacts with the α5β1 integrin). The concentration of cilengitide causing the maximal inhibitory effect on adhesion to vitronectin (i.e., 20 µg/ml), strongly reduced the invasion of matrigel by M14C2/MK18 cells (Fig. 2b) without affecting cell viability (data not shown). Since cilengitide specifically interacts with the αvβ3 and αvβ5 integrins, these results confirmed the relevance of these integrins in melanoma invasiveness. Reference: Int J Cancer. 2015 Mar 15;136(6):E545-58. https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.29252
In vivo activity: In control rats, bone metastases contained tumor cells (representing the soft tissue tumor) within areas of bone resorption corresponding to VCT and MR imaging (Fig. 5a). After treatment with cilengitide, newly formed bone was confirmed on hematoxylin/eosin-stained sections (Fig. 5b) taken from the proximal tibia of the animal, as shown in Fig. 3c. Immunofluorescence analysis in control animals revealed irregular vessels with small diameters, indicated by collagen IV staining in the basal lamina of vessels, which were not colocalized with SMA, along with larger vessels showing collagen IV/SMA colocalization (Fig. 5c). After 4 weeks treatment with cilengitide essentially only small and mesh-like vessels were seen without clear co-localization of SMA and collagen IV (Fig. 5d). Quantification of the immunofluorescent analysis resulted in significantly decreased mean positive area fractions of SMA (p < 0.05) and significantly increased area fractions of collagen IV (p < 0.01) in treated animals as compared to controls (Fig. 6a). The ratio of SMA and collagen IV (treated rats: 0.60/3.32; control rats: 0.83/2.37) was significantly decreased in animals after 4 weeks treatment with cilengitide (p < 0.01), and the mean vessel diameter in cilengitide-treated bone metastases (6.6 μm) was significantly smaller than in control rats (8.8 μm, p < 0.01; Fig. 6b). Reference: Int J Cancer. 2011 May 15;128(10):2453-62. https://pubmed.ncbi.nlm.nih.gov/20648558/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 142.31
Water 15.63 22.24

Preparing Stock Solutions

The following data is based on the product molecular weight 702.7 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. Ruffini F, Graziani G, Levati L, Tentori L, D'Atri S, Lacal PM. Cilengitide downmodulates invasiveness and vasculogenic mimicry of neuropilin 1 expressing melanoma cells through the inhibition of αvβ5 integrin. Int J Cancer. 2015 Mar 15;136(6):E545-58. doi: 10.1002/ijc.29252. Epub 2014 Nov 28. PMID: 25284767. 2. Cheng NC, van Zandwijk N, Reid G. Cilengitide inhibits attachment and invasion of malignant pleural mesothelioma cells through antagonism of integrins αvβ3 and αvβ5. PLoS One. 2014 Mar 3;9(3):e90374. doi: 10.1371/journal.pone.0090374. PMID: 24595274; PMCID: PMC3940880. 3. Bäuerle T, Komljenovic D, Merz M, Berger MR, Goodman SL, Semmler W. Cilengitide inhibits progression of experimental breast cancer bone metastases as imaged noninvasively using VCT, MRI and DCE-MRI in a longitudinal in vivo study. Int J Cancer. 2011 May 15;128(10):2453-62. doi: 10.1002/ijc.25563. PMID: 20648558. 4. Wilisch-Neumann A, Kliese N, Pachow D, Schneider T, Warnke JP, Braunsdorf WE, Böhmer FD, Hass P, Pasemann D, Helbing C, Kirches E, Mawrin C. The integrin inhibitor cilengitide affects meningioma cell motility and invasion. Clin Cancer Res. 2013 Oct 1;19(19):5402-12. doi: 10.1158/1078-0432.CCR-12-0299. Epub 2013 Aug 15. PMID: 23948974.
In vitro protocol: 1. Ruffini F, Graziani G, Levati L, Tentori L, D'Atri S, Lacal PM. Cilengitide downmodulates invasiveness and vasculogenic mimicry of neuropilin 1 expressing melanoma cells through the inhibition of αvβ5 integrin. Int J Cancer. 2015 Mar 15;136(6):E545-58. doi: 10.1002/ijc.29252. Epub 2014 Nov 28. PMID: 25284767. 2. Cheng NC, van Zandwijk N, Reid G. Cilengitide inhibits attachment and invasion of malignant pleural mesothelioma cells through antagonism of integrins αvβ3 and αvβ5. PLoS One. 2014 Mar 3;9(3):e90374. doi: 10.1371/journal.pone.0090374. PMID: 24595274; PMCID: PMC3940880.
In vivo protocol: 1. Bäuerle T, Komljenovic D, Merz M, Berger MR, Goodman SL, Semmler W. Cilengitide inhibits progression of experimental breast cancer bone metastases as imaged noninvasively using VCT, MRI and DCE-MRI in a longitudinal in vivo study. Int J Cancer. 2011 May 15;128(10):2453-62. doi: 10.1002/ijc.25563. PMID: 20648558. 2. Wilisch-Neumann A, Kliese N, Pachow D, Schneider T, Warnke JP, Braunsdorf WE, Böhmer FD, Hass P, Pasemann D, Helbing C, Kirches E, Mawrin C. The integrin inhibitor cilengitide affects meningioma cell motility and invasion. Clin Cancer Res. 2013 Oct 1;19(19):5402-12. doi: 10.1158/1078-0432.CCR-12-0299. Epub 2013 Aug 15. PMID: 23948974.

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https://repositorio.uade.edu.ar/xmlui/handle/123456789/13471

1: Zhang L, Gülses A, Purcz N, Weimer J, Wiltfang J, Açil Y. A comparative assessment of the effects of integrin inhibitor cilengitide on primary culture of head and neck squamous cell carcinoma (HNSCC) and HNSCC cell lines. Clin Transl Oncol. 2019 Jan 10. doi: 10.1007/s12094-018-02025-3. [Epub ahead of print] PubMed PMID: 30632010.

2: Stojanović N, Dekanić A, Paradžik M, Majhen D, Ferenčak K, Ruščić J, Bardak I, Supina C, Tomicic MT, Christmann M, Osmak M, Ambriović-Ristov A. Differential Effects of Integrin αv Knockdown and Cilengitide on Sensitization of Triple-Negative Breast Cancer and Melanoma Cells to Microtubule Poisons. Mol Pharmacol. 2018 Dec;94(6):1334-1351. doi: 10.1124/mol.118.113027. Epub 2018 Sep 27. PubMed PMID: 30262596.

3: Xu HL, Yang JJ, ZhuGe DL, Lin MT, Zhu QY, Jin BH, Tong MQ, Shen BX, Xiao J, Zhao YZ. Glioma-Targeted Delivery of a Theranostic Liposome Integrated with Quantum Dots, Superparamagnetic Iron Oxide, and Cilengitide for Dual-Imaging Guiding Cancer Surgery. Adv Healthc Mater. 2018 May;7(9):e1701130. doi: 10.1002/adhm.201701130. Epub 2018 Jan 19. PubMed PMID: 29350498.

4: Massabeau C, Khalifa J, Filleron T, Modesto A, Bigay-Gamé L, Plat G, Dierickx L, Aziza R, Rouquette I, Gomez-Roca C, Mounier M, Delord JP, Toulas C, Olivier P, Chatelut E, Mazières J, Cohen-Jonathan Moyal E. Continuous Infusion of Cilengitide Plus Chemoradiotherapy for Patients With Stage III Non-Small-cell Lung Cancer: A Phase I Study. Clin Lung Cancer. 2018 May;19(3):e277-e285. doi: 10.1016/j.cllc.2017.11.002. Epub 2017 Nov 21. PubMed PMID: 29221762.

5: Garciarena CD, McHale TM, Martin-Loeches I, Kerrigan SW. Pre-emptive and therapeutic value of blocking bacterial attachment to the endothelial alphaVbeta3 integrin with cilengitide in sepsis. Crit Care. 2017 Sep 26;21(1):246. doi: 10.1186/s13054-017-1838-3. PubMed PMID: 28946901; PubMed Central PMCID: PMC5613315.

6: Cedra S, Wiegand S, Kolb M, Dietz A, Wichmann G. Reduced Cytokine Release in Ex Vivo Response to Cilengitide and Cetuximab Is a Marker for Improved Survival of Head and Neck Cancer Patients. Cancers (Basel). 2017 Sep 5;9(9). pii: E117. doi: 10.3390/cancers9090117. PubMed PMID: 28872582; PubMed Central PMCID: PMC5615332.

7: Jiao Z, Li Y, Pang H, Zheng Y, Zhao Y. Pep-1 peptide-functionalized liposome to enhance the anticancer efficacy of cilengitide in glioma treatment. Colloids Surf B Biointerfaces. 2017 Oct 1;158:68-75. doi: 10.1016/j.colsurfb.2017.03.058. Epub 2017 Apr 13. PubMed PMID: 28672205.

8: Nalkiran HS, McDonald KL. Is neuroglial antigen 2 a potential contributor to cilengitide response in glioblastoma? J Cancer Res Ther. 2017 Apr-Jun;13(2):329-336. doi: 10.4103/0973-1482.188438. PubMed PMID: 28643756.

9: Haddad T, Qin R, Lupu R, Satele D, Eadens M, Goetz MP, Erlichman C, Molina J. A phase I study of cilengitide and paclitaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2017 Jun;79(6):1221-1227. doi: 10.1007/s00280-017-3322-9. Epub 2017 May 5. PubMed PMID: 28477227.

10: Wichmann G, Cedra S, Schlegel D, Kolb M, Wiegand S, Boehm A, Hofer M, Dietz A. Cilengitide and Cetuximab Reduce Cytokine Production and Colony Formation of Head and Neck Squamous Cell Carcinoma Cells Ex Vivo. Anticancer Res. 2017 Feb;37(2):521-527. PubMed PMID: 28179297.

11: Kurozumi K, Ishida J, Ichikawa T, Date I. [Cilengitide]. Nihon Rinsho. 2016 Sep;74 Suppl 7:672-676. Japanese. PubMed PMID: 30634832.

12: Dolgos H, Freisleben A, Wimmer E, Scheible H, Krätzer F, Yamagata T, Gallemann D, Fluck M. In vitro and in vivo drug disposition of cilengitide in animals and human. Pharmacol Res Perspect. 2016 Mar 17;4(2):e00217. doi: 10.1002/prp2.217. eCollection 2016 Apr. PubMed PMID: 27069630; PubMed Central PMCID: PMC4804314.

13: Khasraw M, Lee A, McCowatt S, Kerestes Z, Buyse ME, Back M, Kichenadasse G, Ackland S, Wheeler H. Cilengitide with metronomic temozolomide, procarbazine, and standard radiotherapy in patients with glioblastoma and unmethylated MGMT gene promoter in ExCentric, an open-label phase II trial. J Neurooncol. 2016 May;128(1):163-171. doi: 10.1007/s11060-016-2094-0. Epub 2016 Mar 2. PubMed PMID: 26935578.

14: Weller M, Nabors LB, Gorlia T, Leske H, Rushing E, Bady P, Hicking C, Perry J, Hong YK, Roth P, Wick W, Goodman SL, Hegi ME, Picard M, Moch H, Straub J, Stupp R. Cilengitide in newly diagnosed glioblastoma: biomarker expression and outcome. Oncotarget. 2016 Mar 22;7(12):15018-32. doi: 10.18632/oncotarget.7588. PubMed PMID: 26918452; PubMed Central PMCID: PMC4924768.

15: Lu LQ, Fang T, Zhou D, Tong XX, Wu J, Yi L. [Efficiency of integrin αvβ3 inhibitor Cilengitide in acute cerebral ischemia in rats]. Zhonghua Yi Xue Za Zhi. 2016 Feb 23;96(7):559-64. doi: 10.3760/cma.j.issn.0376-2491.2016.07.015. Chinese. PubMed PMID: 26902199.

16: Zhao YZ, Lin Q, Wong HL, Shen XT, Yang W, Xu HL, Mao KL, Tian FR, Yang JJ, Xu J, Xiao J, Lu CT. Glioma-targeted therapy using Cilengitide nanoparticles combined with UTMD enhanced delivery. J Control Release. 2016 Feb 28;224:112-125. doi: 10.1016/j.jconrel.2016.01.015. Epub 2016 Jan 11. PubMed PMID: 26792571.

17: Tucci M, Stucci S, Felici C, Cafforio P, Resta L, Rossi R, Silvestris F. Cilengitide restrains the osteoclast-like bone resorbing activity of myeloma plasma cells. Br J Haematol. 2016 Apr;173(1):59-69. doi: 10.1111/bjh.13922. Epub 2016 Jan 5. PubMed PMID: 26728969.

18: Chillà A, Bianconi D, Geetha N, Dorda A, Poettler M, Unseld M, Sykoutri D, Redlich K, Zielinski CC, Prager GW. Effects of cilengitide in osteoclast maturation and behavior. Exp Cell Res. 2015 Sep 10;337(1):68-75. doi: 10.1016/j.yexcr.2015.07.018. Epub 2015 Jul 21. PubMed PMID: 26209605.

19: O'Donnell PH, Karovic S, Karrison TG, Janisch L, Levine MR, Harris PJ, Polite BN, Cohen EE, Fleming GF, Ratain MJ, Maitland ML. Serum C-Telopeptide Collagen Crosslinks and Plasma Soluble VEGFR2 as Pharmacodynamic Biomarkers in a Trial of Sequentially Administered Sunitinib and Cilengitide. Clin Cancer Res. 2015 Nov 15;21(22):5092-9. doi: 10.1158/1078-0432.CCR-15-0427. Epub 2015 Jul 21. PubMed PMID: 26199386; PubMed Central PMCID: PMC4677671.

20: Lam S, Li G, Zada G, Pelargos P, Choy W, Yang I, Smith ZA. Neurosurgery Concepts: Key perspectives on quality of life in children with spina bifida, cilengitide for the treatment of newly diagnosed glioblastoma, surgery and stereotactic radiosurgery in the management of intracranial metastasis, Gamma Knife radiosurgery in patients with Neurofibromatosis Type 2, patient misconceptions on the diagnosis and treatment of lumbar spondylosis. Surg Neurol Int. 2015 Jun 18;6:110. doi: 10.4103/2152-7806.159075. eCollection 2015. PubMed PMID: 26167362; PubMed Central PMCID: PMC4483781.



Additional Information

Related CAS#
199807-35-7 (TFA salt); 188968-51-6 (free base).

Recent publications related to cilengitide supplied by MedKoo
1: Cheshenko N, Trepanier JB, González PA, Eugenin EA, Jacobs WR Jr, Herold BC. Herpes simplex virus type 2 glycoprotein H interacts with integrin αvβ3 to facilitate viral entry and calcium signaling in human genital tract epithelial cells. J Virol. 2014 Sep 1;88(17):10026-38. doi: 10.1128/JVI.00725-14. Epub 2014  Jun 18. PubMed PMID: 24942591; PubMed Central PMCID: PMC4136333.
1: Cheshenko N, Trepanier JB, González PA, Eugenin EA, Jacobs WR Jr, Herold BC. Herpes simplex virus type 2 glycoprotein H interacts with integrin αvβ3 to facilitate viral entry and calcium signaling in human genital tract epithelial cells. J Virol. 2014 Sep 1;88(17):10026-38. doi: 10.1128/JVI.00725-14. Epub 2014  Jun 18. PubMed PMID: 24942591; PubMed Central PMCID: PMC4136333.