Tivantinib
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MedKoo CAT#: 200283

CAS#: 905854-02-6

Description: Tivantinib (ARQ-197) is an orally bioavailable small molecule inhibitor of c-Met with potential antineoplastic activity. c-Met inhibitor ARQ 197 binds to the c-Met protein and disrupts c-Met signal transduction pathways, which may induce cell death in tumor cells overexpressing c-Met protein or expressing consitutively activated c-Met protein. c-Met protein, the product of the proto-oncogene c-Met, is a receptor tyrosine kinase also known as hepatocyte growth factor receptor (HGFR); this protein is overexpressed or mutated in many tumor cell types and plays key roles in tumor cell proliferation, survival, invasion, and metastasis, and tumor angiogenesis.


Price and Availability

Size
Price

5mg
USD 195
Size
Price

10mg
USD 295
Size
Price

Tivantinib, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 200283
Name: Tivantinib
CAS#: 905854-02-6
Chemical Formula: C23H19N3O2
Exact Mass: 369.14773
Molecular Weight: 369.41
Elemental Analysis: C, 74.78; H, 5.18; N, 11.37; O, 8.66


Synonym: ARQ197; ARQ 197; ARQ-197; Tivantinib

IUPAC/Chemical Name: (3R,4R)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione

InChi Key: UCEQXRCJXIVODC-PMACEKPBSA-N

InChi Code: InChI=1S/C23H19N3O2/c27-22-19(16-11-24-18-9-2-1-7-14(16)18)20(23(28)25-22)17-12-26-10-4-6-13-5-3-8-15(17)21(13)26/h1-3,5,7-9,11-12,19-20,24H,4,6,10H2,(H,25,27,28)/t19-,20-/m0/s1

SMILES Code: O=C([C@@H](C1=CN2CCCC3=C2C1=CC=C3)[C@@H]4C5=CNC6=C5C=CC=C6)NC4=O


Technical Data

Appearance:
white solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Safety Data Sheet (MSDS):

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).

Harmonized System Code:
293490


References

1: Kang YK, Muro K, Ryu MH, Yasui H, Nishina T, Ryoo BY, Kamiya Y, Akinaga S, Boku N. A phase II trial of a selective c-Met inhibitor tivantinib (ARQ 197) monotherapy as a second- or third-line therapy in the patients with metastatic gastric cancer. Invest New Drugs. 2013 Dec 15. [Epub ahead of print] PubMed PMID: 24337769.

2: Previdi S, Scolari F, Chilà R, Ricci F, Abbadessa G, Broggini M. Combination of the c-Met inhibitor tivantinib and zoledronic acid prevents tumor bone engraftment and inhibits progression of established bone metastases in a breast xenograft model. PLoS One. 2013 Nov 18;8(11):e79101. doi: 10.1371/journal.pone.0079101. eCollection 2013. PubMed PMID: 24260160; PubMed Central PMCID: PMC3832513.

3: Remsing Rix LL, Kuenzi BM, Luo Y, Remily-Wood E, Kinose F, Wright G, Li J, Koomen JM, Haura EB, Lawrence HR, Rix U. GSK3 Alpha and Beta Are New Functionally Relevant Targets of Tivantinib in Lung Cancer Cells. ACS Chem Biol. 2013 Nov 20. [Epub ahead of print] PubMed PMID: 24215125.

4: Yamamoto N, Murakami H, Hayashi H, Fujisaka Y, Hirashima T, Takeda K, Satouchi M, Miyoshi K, Akinaga S, Takahashi T, Nakagawa K. CYP2C19 genotype-based phase I studies of a c-Met inhibitor tivantinib in combination with erlotinib, in advanced/metastatic non-small cell lung cancer. Br J Cancer. 2013 Nov 26;109(11):2803-9. doi: 10.1038/bjc.2013.588. Epub 2013 Oct 29. PubMed PMID: 24169346; PubMed Central PMCID: PMC3844902.

5: Rimassa L, Bruix J, Broggini M, Santoro A. Tivantinib (ARQ197) displays cytotoxic activity that is independent of its ability to bind MET--letter. Clin Cancer Res. 2013 Aug 1;19(15):4290. doi: 10.1158/1078-0432.CCR-13-1321. Epub 2013 Jun 13. PubMed PMID: 23766362.

6: Michieli P, Basilico C, Pennacchietti S. Tivantinib (ARQ197) displays cytotoxic activity that is independent of its ability to bind MET--response. Clin Cancer Res. 2013 Aug 1;19(15):4291. doi: 10.1158/1078-0432.CCR-13-1534. Epub 2013 Jun 13. PubMed PMID: 23766360.

7: Michieli P, Di Nicolantonio F. Targeted therapies: Tivantinib--a cytotoxic drug in MET inhibitor's clothes? Nat Rev Clin Oncol. 2013 Jul;10(7):372-4. doi: 10.1038/nrclinonc.2013.86. Epub 2013 May 28. PubMed PMID: 23712183.

8: Katayama R, Aoyama A, Yamori T, Qi J, Oh-hara T, Song Y, Engelman JA, Fujita N. Cytotoxic activity of tivantinib (ARQ 197) is not due solely to c-MET inhibition. Cancer Res. 2013 May 15;73(10):3087-96. doi: 10.1158/0008-5472.CAN-12-3256. Epub 2013 Apr 18. PubMed PMID: 23598276; PubMed Central PMCID: PMC3759033.

9: Basilico C, Pennacchietti S, Vigna E, Chiriaco C, Arena S, Bardelli A, Valdembri D, Serini G, Michieli P. Tivantinib (ARQ197) displays cytotoxic activity that is independent of its ability to bind MET. Clin Cancer Res. 2013 May 1;19(9):2381-92. doi: 10.1158/1078-0432.CCR-12-3459. Epub 2013 Mar 26. PubMed PMID: 23532890.

10: Feldman DR, Einhorn LH, Quinn DI, Loriot Y, Joffe JK, Vaughn DJ, Fléchon A, Hajdenberg J, Halim AB, Zahir H, Motzer RJ. A phase 2 multicenter study of tivantinib (ARQ 197) monotherapy in patients with relapsed or refractory germ cell tumors. Invest New Drugs. 2013 Aug;31(4):1016-22. doi: 10.1007/s10637-013-9934-y. Epub 2013 Feb 17. PubMed PMID: 23417696.

11: Rimassa L, Personeni N, Simonelli M, Santoro A. Tivantinib: a new promising mesenchymal-epithelial transition factor inhibitor in the treatment of hepatocellular carcinoma. Future Oncol. 2013 Feb;9(2):153-65. doi: 10.2217/fon.12.188. PubMed PMID: 23414466.

12: Yamamoto N, Murakami H, Nishina T, Hirashima T, Sugio K, Muro K, Takahashi T, Naito T, Yasui H, Akinaga S, Koh Y, Boku N. The effect of CYP2C19 polymorphism on the safety, tolerability, and pharmacokinetics of tivantinib (ARQ 197): results from a phase I trial in advanced solid tumors. Ann Oncol. 2013 Jun;24(6):1653-9. doi: 10.1093/annonc/mdt014. Epub 2013 Feb 14. PubMed PMID: 23413279.

13: Broggini M, Garassino MC, Damia G. Evaluation of safety and efficacy of tivantinib in the treatment of inoperable or recurrent non-small-cell lung cancer. Cancer Manag Res. 2013;5:15-20. doi: 10.2147/CMAR.S29995. Epub 2013 Jan 17. PubMed PMID: 23378782; PubMed Central PMCID: PMC3559079.

14: Santoro A, Simonelli M, Rodriguez-Lope C, Zucali P, Camacho LH, Granito A, Senzer N, Rimassa L, Abbadessa G, Schwartz B, Lamar M, Savage RE, Bruix J. A Phase-1b study of tivantinib (ARQ 197) in adult patients with hepatocellular carcinoma and cirrhosis. Br J Cancer. 2013 Jan 15;108(1):21-4. doi: 10.1038/bjc.2012.556. Epub 2013 Jan 3. PubMed PMID: 23287988; PubMed Central PMCID: PMC3553536.

15: Santoro A, Rimassa L, Borbath I, Daniele B, Salvagni S, Van Laethem JL, Van Vlierberghe H, Trojan J, Kolligs FT, Weiss A, Miles S, Gasbarrini A, Lencioni M, Cicalese L, Sherman M, Gridelli C, Buggisch P, Gerken G, Schmid RM, Boni C, Personeni N, Hassoun Z, Abbadessa G, Schwartz B, Von Roemeling R, Lamar ME, Chen Y, Porta C. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study. Lancet Oncol. 2013 Jan;14(1):55-63. doi: 10.1016/S1470-2045(12)70490-4. Epub 2012 Nov 20. PubMed PMID: 23182627.

16: Trojan J, Zeuzem S. Tivantinib in hepatocellular carcinoma. Expert Opin Investig Drugs. 2013 Jan;22(1):141-7. doi: 10.1517/13543784.2013.741586. Epub 2012 Nov 21. Review. PubMed PMID: 23167786.

17: Wagner AJ, Goldberg JM, Dubois SG, Choy E, Rosen L, Pappo A, Geller J, Judson I, Hogg D, Senzer N, Davis IJ, Chai F, Waghorne C, Schwartz B, Demetri GD. Tivantinib (ARQ 197), a selective inhibitor of MET, in patients with microphthalmia transcription factor-associated tumors: results of a multicenter phase 2 trial. Cancer. 2012 Dec 1;118(23):5894-902. doi: 10.1002/cncr.27582. Epub 2012 May 17. PubMed PMID: 22605650.

18: Goldman JW, Laux I, Chai F, Savage RE, Ferrari D, Garmey EG, Just RG, Rosen LS. Phase 1 dose-escalation trial evaluating the combination of the selective MET (mesenchymal-epithelial transition factor) inhibitor tivantinib (ARQ 197) plus erlotinib. Cancer. 2012 Dec 1;118(23):5903-11. doi: 10.1002/cncr.27575. Epub 2012 May 17. PubMed PMID: 22605616.

19: Scagliotti GV, Novello S, Schiller JH, Hirsh V, Sequist LV, Soria JC, von Pawel J, Schwartz B, Von Roemeling R, Sandler AB. Rationale and design of MARQUEE: a phase III, randomized, double-blind study of tivantinib plus erlotinib versus placebo plus erlotinib in previously treated patients with locally advanced or metastatic, nonsquamous, non-small-cell lung cancer. Clin Lung Cancer. 2012 Sep;13(5):391-5. doi: 10.1016/j.cllc.2012.01.003. Epub 2012 Mar 21. PubMed PMID: 22440336.

20: Previdi S, Abbadessa G, Dalò F, France DS, Broggini M. Breast cancer-derived bone metastasis can be effectively reduced through specific c-MET inhibitor tivantinib (ARQ 197) and shRNA c-MET knockdown. Mol Cancer Ther. 2012 Jan;11(1):214-23. doi: 10.1158/1535-7163.MCT-11-0277. Epub 2011 Oct 25. PubMed PMID: 22027690.s