WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201920
Description: MKC-1 is an orally bioavailable, small-molecule, bisindolylmaleimide cell cycle inhibitor with potential antineoplastic activity. MKC-1 and its metabolites inhibit tubulin polymerization, blocking the formation of the mitotic spindle, which may result in cell cycle arrest at the G2/M phase and apoptosis. In addition, this agent has been shown to inhibit the activities of the oncogenic kinase Akt, the mTOR pathway, and importin-beta, a protein essential to the transport of other proteins from the cytosol into the nucleus. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus). (Last updated:: 4/26/2016).
MedKoo Cat#: 201920
Chemical Formula: C22H16N4O4
Exact Mass: 400.11716
Molecular Weight: 400.39
Elemental Analysis: C, 66.00; H, 4.03; N, 13.99; O, 15.98
Synonym: MKC1; MKC 1; MKC-1; R 440; R-440; R440; Ro 317453; Ro-317453; Ro317453
IUPAC/Chemical Name: 3-(1-methyl-1H-indol-3-yl)-4-(1-methyl-6-nitro-1H-indol-3-yl)-1H-pyrrole-2,5-dione
InChi Key: OVSKGTONMLKNPZ-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H16N4O4/c1-24-10-15(13-5-3-4-6-17(13)24)19-20(22(28)23-21(19)27)16-11-25(2)18-9-12(26(29)30)7-8-14(16)18/h3-11H,1-2H3,(H,23,27,28)
SMILES Code: O=C(C(C1=CN(C)C2=C1C=CC=C2)=C3C4=CN(C)C5=C4C=CC([N+]([O-])=O)=C5)NC3=O
Appearance: Solid powder
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
The following data is based on the product molecular weight 400.39 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|
1: Zagouri F, Sergentanis TN, Chrysikos D, Filipits M, Bartsch R. mTOR inhibitors in breast cancer: A systematic review. Gynecol Oncol. 2012 Dec;127(3):662-72. doi: 10.1016/j.ygyno.2012.08.040. Epub 2012 Sep 9. PubMed PMID: 22967800.
2: Faris JE, Arnott J, Zheng H, Ryan DP, Abrams TA, Blaszkowsky LS, Clark JW, Enzinger PC, Hezel AF, Ng K, Wolpin BM, Kwak EL. A phase 2 study of oral MKC-1, an inhibitor of importin-β, tubulin, and the mTOR pathway in patients with unresectable or metastatic pancreatic cancer. Invest New Drugs. 2012 Aug;30(4):1614-20. doi: 10.1007/s10637-011-9708-3. Epub 2011 Jul 29. PubMed PMID: 21800081.
3: Tevaarwerk A, Wilding G, Eickhoff J, Chappell R, Sidor C, Arnott J, Bailey H, Schelman W, Liu G. Phase I study of continuous MKC-1 in patients with advanced or metastatic solid malignancies using the modified Time-to-Event Continual Reassessment Method (TITE-CRM) dose escalation design. Invest New Drugs. 2012 Jun;30(3):1039-45. Epub 2011 Jan 12. PubMed PMID: 21225315; PubMed Central PMCID: PMC3139017.
4: Wang M, Gao M, Miller KD, Sledge GW, Hutchins GD, Zheng QH. The first design and synthesis of [11C]MKC-1 ([11C]Ro 31-7453), a new potential PET cancer imaging agent. Nucl Med Biol. 2010 Oct;37(7):763-75. PubMed PMID: 20870151.
5: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Oct;30(8):643-72. PubMed PMID: 19088949.
6: Worker C. AACR -91st meeting. Interview with Dr Lars Breimer. IDrugs. 2000 Jul;3(7):723-5. PubMed PMID: 16080035.
7: BayÃ©s M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2005 Mar;27(2):145-59. PubMed PMID: 15834466.
8: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Jun;26(5):357-91. PubMed PMID: 15319815.
9: Dupont J, Bienvenu B, Aghajanian C, Pezzulli S, Sabbatini P, Vongphrachanh P, Chang C, Perkell C, Ng K, Passe S, Breimer L, Zhi J, DeMario M, Spriggs D, Soignet SL. Phase I and pharmacokinetic study of the novel oral cell-cycle inhibitor Ro 31-7453 in patients with advanced solid tumors. J Clin Oncol. 2004 Aug 15;22(16):3366-74. PubMed PMID: 15310782.
10: Salazar R, Bissett D, Twelves C, Breimer L, DeMario M, Campbell S, Zhi J, Ritland S, Cassidy J. A phase I clinical and pharmacokinetic study of Ro 31-7453 given as a 7- or 14-day oral twice daily schedule every 4 weeks in patients with solid tumors. Clin Cancer Res. 2004 Jul 1;10(13):4374-82. PubMed PMID: 15240525.
11: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Jun;25(5):387-408. PubMed PMID: 12851663.
12: Troy TC, Turksen K. In vitro characteristics of early epidermal progenitors isolated from keratin 14 (K14)-deficient mice: insights into the role of keratin 17 in mouse keratinocytes. J Cell Physiol. 1999 Sep;180(3):409-21. PubMed PMID: 10430181.
Phase 2 clinical trial results: 20 of an original target of 33 patients were accrued, with a median age of 61 (range 44-81). No objective responses were observed, with one patient demonstrating stable disease. Overall survival was 101 days from the start of MKC-1 administration, and median time to progression was 42 days. The most common adverse events listed as related or possibly related to MKC-1 administration were hematologic toxicities and fatigue. One patient developed grade 5 (fatal) pancytopenia. Grade 3 and 4 events included cytopenias (lymphopenia, anemia), hyperbilirubinemia, pneumonia, mucositis, fatigue, infusion reaction, anorexia, and hypoalbuminemia. CONCLUSIONS: MKC-1 administration was associated with substantial toxicity and did not demonstrate sufficient activity in patients with advanced pancreatic cancer to justify further exploration in this patient population. (source: Invest New Drugs. 2012 Aug;30(4):1614-20. ).