This is an open-label study to determine the highest dose of MKC-1 that may be administered daily on a continuous basis for patients with advanced or refractory solid tumors.

Start Date01 Mar 2008

Sponsor / Collaborator

CASI Pharmaceuticals, Inc.

NCT00607607 / CompletedPhase 2

A Phase 2 Study of Oral MKC-1 Administered Twice Daily for 14 Consecutive Days Every 4 Weeks in Patients With Recurrent or Resistant Epithelial Ovarian Cancer or Advanced Endometrial Cancer

Patients will be treated with MKC-1, twice daily for 14 consecutive days every four weeks (a cycle of MKC-1 chemotherapy), until disease progression or unacceptable toxicities. Patients will be stratified to Arm A (ovarian cancer) or Arm B (endometrial cancer), and will receive identical treatment regimens.

Start Date01 Jan 2008

Sponsor / Collaborator

CASI Pharmaceuticals, Inc.

NCT00568646 / CompletedPhase 2

A Phase 2 Study of Oral MKC 1, Administered Twice Daily for 14 Consecutive Days in a 28-Day Cycle, in Patients With Unresectable or Metastatic Pancreatic Cancer Who Have Failed at Least One Prior Chemotherapy Regimen in Either the Neoadjuvant, Adjuvant, or First-line Metastatic Setting

To determine the antitumor activity of MKC-1 in patients with unresectable or metastatic pancreatic cancer who have failed at least one prior chemotherapy regimen in either the neoadjuvant, adjuvant, or first-line metastatic setting

Start Date01 Nov 2007

Sponsor / Collaborator

CASI Pharmaceuticals, Inc.

100 Clinical Results associated with MKC-1

100 Translational Medicine associated with MKC-1

100 Patents (Medical) associated with MKC-1

Literatures (Medical) associated with MKC-1

01 Aug 2012·Investigational new drugsQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: Eunice L. Kwak ; Jeffrey W. Clark ; Brian M. Wolpin ; Jamie Arnott ; Jason E. Faris ; Lawrence S. Blaszkowsky ; Hui Zheng ; David P. Ryan ; Aram F. Hezel ; Kimmie Ng ; Thomas A. Abrams ; Peter C. Enzinger

BACKGROUND:

MKC-1 is an orally available cell cycle inhibitor with downstream targets that include tubulin and the importin-β family. We conducted an open-label Phase II study with MKC-1 in patients with advanced pancreatic cancer.

METHODS:

Eligibility criteria included unresectable or metastatic pancreatic cancer, performance status of 1 or better, and failure of at least one prior regimen of chemotherapy. MKC-1 was administered orally, twice daily, initially at 100 mg/m(2) dosing for 14 consecutive days of a 28-day cycle. This schedule was modified during the trial to fixed and continuous dosing of 150 mg per day.

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.

01 Jun 2012·Investigational new drugsQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: Carolyn Sidor ; Jamie Arnott ; Rick Chappell ; Amye Tevaarwerk ; William Schelman ; Jens Eickhoff ; Howard Bailey ; Glenn Liu ; George Wilding

BACKGROUND:

MKC-1 is an oral cell-cycle inhibitor with broad antitumor activity in preclinical models. Clinical studies demonstrated modest antitumor activity using intermittent dosing schedule, however additional preclinical data suggested continuous dosing could be efficacious with additional effects against the mTor/AKT pathway. The primary objectives were to determine the maximum tolerated dose (MTD) and response of continuous MKC-1. Secondary objectives included characterizing the dose limiting toxicities (DLTs) and pharmacokinetics (PK).

METHODS:

Patients with solid malignancies were eligible, if they had measurable disease, ECOG PS ≤1, and adequate organ function. Exclusions included brain metastases and inability to receive oral drug. MKC-1 was dosed twice daily, continuously in 28-day cycles. Other medications were eliminated if there were possible drug interactions. Doses were assigned using a TITE-CRM algorithm following enrollment of the first 3 pts. Disease response was assessed every 8 weeks.

RESULTS:

Between 5/08-9/09, 24 patients enrolled (15 M/9 F, median 58 years, range 44-77). Patients 1-3 received 120 mg/d of MKC-1; patients 4-24 were dosed per the TITE-CRM algorithm: 150 mg [n = 1], 180 [2], 200 [1], 230 [1], 260 [5], 290 [6], 320 [5]. The median time on drug was 8 weeks (range 4-28). The only DLT occurred at 320 mg (grade 3 fatigue). Stable disease occurred at 150 mg/d (28 weeks; RCC) and 320 mg/d (16 weeks; breast, parotid). Escalation halted at 320 mg/d. Day 28 pharmacokinetics indicated absorption and active metabolites.

CONCLUSION:

Continuous MKC-1 was well-tolerated; there were no RECIST responses, although clinical benefit occurred in 3/24 pts. Dose escalation stopped at 320 mg/d, and this is the MTD as defined by the CRM dose escalation algorithm; this cumulative dose/cycle exceeds that determined from intermittent dosing studies. A TITE-CRM allowed for rapid dose escalation and was able to account for late toxicities with continuous dosing via a modified algorithm.

01 Oct 2010·Nuclear medicine and biologyQ4 · MEDICINE

The first design and synthesis of [11C]MKC-1 ([11C]Ro 31-7453), a new potential PET cancer imaging agent

Q4 · MEDICINE

Article

Author: Gao, Mingzhang ; Hutchins, Gary D. ; Miller, Kathy D. ; Wang, Min ; Sledge, George W. ; Zheng, Qi-Huang

Bisindolylmaleimide MKC-1 (formerly known as Ro 31-7453) is a novel, orally active, small-molecule, cell cycle inhibitor with broad-spectrum antitumor effects. [(11)C]MKC-1 ([(11)C]Ro 31-7453) was first designed and synthesized as a new potential positron emission tomography cancer imaging agent through two different strategies. The first strategy was to prepare a carbon-11-labeled bisindolyl maleic anhydride intermediate followed by the conversion to maleimide. The second strategy involved the condensation of either carbon-11-labeled indole-3-acetamides with indole-3-glyoxalates, or indole-3-acetamides with carbon-11-labeled indole-3-glyoxalates. The radiochemical yields were 15-30%, decay corrected to end of bombardment (EOB), based on [(11)C]CO(2). The specific activity was 222-296 GBq/μmol at EOB and 111-148 GBq/μmol at the end of synthesis, respectively.

News (Medical) associated with MKC-1

05 Feb 2010

·www.biospace.com

EntreMed, Inc. Raises Additional $2.5 Million In Registered Direct Offering

ROCKVILLE, Md., Feb. 4 /PRNewswire-FirstCall/ -- EntreMed, Inc. today announced that it completed a registered direct offering of 3,846,154 shares of its common stock, at a purchase price of $0.65 per share, to a single accredited institutional investor. The sale resulted in gross proceeds to the Company of $2.5 million. The terms of the purchase were set forth in a stock purchase agreement entered into by the parties on February 3, 2010. The per share purchase price reflects a 10% discount to the five-day average closing sale price ending on February 2, 2010. EntreMed plans to use the net proceeds of the offering, which are expected to be approximately $2.3 million after deducting the placement agent's fee and estimated offering expenses payable by EntreMed, to further clinical development of its Aurora A/angiogenic kinase inhibitor, ENMD-2076, and for other general corporate purposes. This press release does not and shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities, nor shall there be any sale of the securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any state. About EntreMed EntreMed, Inc. is a clinical-stage pharmaceutical company committed to developing primarily ENMD-2076, a selective angiogenic kinase inhibitor, for the treatment of cancer. ENMD-2076 is currently in Phase 1 studies in advanced cancers, multiple myeloma, and leukemia. The Company's other therapeutic candidates include MKC-1, an oral cell-cycle regulator with activity against the mTOR pathway currently in multiple Phase 2 clinical trials for cancer, and ENMD-1198, a novel antimitotic agent currently in Phase 1 studies in advanced cancers. The Company also has an approved IND application for Panzem(R) in rheumatoid arthritis. Additional information about EntreMed is available on the Company's web site at and in various filings with the Securities and Exchange Commission. CONTACT: Ginny Dunn, Associate Director, Corporate Communications & Investor Relations of EntreMed, Inc., +1-240-864-2643 Web site:

16 Oct 2007

·www.biospace.com

EntreMed, Inc. Appoints Senior Vice President of Research and Development Dr. Kenneth W. Bair Joins Senior Management Team

ROCKVILLE, Md., Oct. 16 /PRNewswire-FirstCall/ -- EntreMed, Inc. , a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, today announced that Kenneth W. Bair, Ph.D. has been appointed its Senior Vice President, Research and Development. Dr. Bair has also been elected an executive officer of EntreMed by the Board of Directors, reporting to James S. Burns, President & CEO. (Logo: ) Dr. Bair brings to EntreMed over 25 years of management experience in oncology drug discovery, development and chemistry. Prior to joining EntreMed, Dr. Bair served as Senior Vice President and Head, BioPharmaceuticals Research at Chiron Corporation in Emeryville, California. Prior to joining Chiron Corporation in 2003, Dr. Bair was Vice President, Discovery Oncology at Pharmacia Corporation in Peapack, New Jersey. From 1982 until joining Pharmacia, Dr. Bair held positions of increasing responsibility within the pharmaceutical industry, including Unit Head of Oncology at Novartis Pharmaceuticals Corporation and Executive Director and Head, Oncology Research Program, Sandoz Pharmaceuticals Corporation; and various oncology research positions at Burroughs Wellcome, Research Triangle Park, North Carolina. Dr. Bair received his Ph.D. in organic chemistry from Brandeis University, Waltham, Massachusetts, and was a Postdoctoral Fellow at the Massachusetts Institute of Technology, Cambridge, Massachusetts. Dr. Bair commented on his appointment at EntreMed, "I am delighted to be joining the EntreMed team. The Company has extensive scientific expertise in angiogenesis, cell cycle regulation, kinase inhibition and inflammation, which provide a strong foundation for building a leading oncology franchise. EntreMed's pipeline of HIF-1 alpha and kinase inhibitors fit well with my background and research interests. I look forward to leading the advancement of EntreMed's mechanism-based drugs for the treatment of cancer and inflammatory diseases." James S. Burns, EntreMed President & CEO commented, "I am very pleased to welcome Ken to EntreMed's leadership team. Ken joins EntreMed with a strong oncology research and development background in large pharmaceutical and biotech companies, experience that will be instrumental in leading EntreMed into its next phase of development." Mr. Burns continued, "Ken has a solid track record in identifying and developing oncology compounds. As Senior Vice President of Research and Development, Ken will play a critical role in leading the development of our ongoing research programs, prioritizing the existing portfolio, and identifying new compounds for our pipeline in order to select the best programs based on the strength of the data and their prospective competitive position." About EntreMed EntreMed, Inc. is a clinical-stage pharmaceutical company developing therapeutic candidates primarily for the treatment of cancer and inflammation. Panzem(R) NCD (2-methoxyestradiol or 2ME2) is currently in multiple Phase 2 clinical trials for cancer. MKC-1, an oral cell-cycle regulator, is in multiple Phase 1 and 2 studies for cancer. ENMD-1198, a novel tubulin-binding agent, is in Phase 1 studies in advanced cancers. Panzem(R) is also in preclinical development for rheumatoid arthritis, and ENMD-2076, a dual-acting Aurora-angiogenesis inhibitor, is in preclinical development for cancer. EntreMed's goal is to develop and commercialize new compounds based on the Company's expertise in angiogenesis, cell-cycle regulation and inflammation - processes vital to the treatment of cancer and other diseases, such as rheumatoid arthritis. Additional information about EntreMed is available on the Company's web site at and in various filings with the Securities and Exchange Commission. Forward Looking Statements This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act with respect to the outlook for expectations for future financial or business performance (including the timing of royalty revenues and future R&D expenditures), strategies, expectations and goals. Forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Forward-looking statements speak only as of the date they are made, and no duty to update forward-looking statements is assumed. Actual results could differ materially from those currently anticipated due to a number of factors, including those set forth in Securities and Exchange Commission filings under "Risk Factors," including risks relating to the need for additional capital and the uncertainty of additional funding; variations in actual sales of Thalomid(R), risks associated with the Company's product candidates; the early-stage products under development; results in preclinical models are not necessarily indicative of clinical results, uncertainties relating to preclinical and clinical trials; success in the clinical development of any products; dependence on third parties; future capital needs; and risks relating to the commercialization, if any, of the Company's proposed products (such as marketing, safety, regulatory, patent, product liability, supply, competition and other risks). CONTACT: Ginny Dunn, Associate Director, Corporate Communications & Investor Relations of EntreMed, Inc., +1-240-864-2643 Web site:

09 Aug 2006

·www.biospace.com

EntreMed, Inc. Reports Second Quarter 2006

ROCKVILLE, Md., Aug. 9 /PRNewswire-FirstCall/ -- EntreMed, Inc. , a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, today reported results for the three and six-month periods ending June 30, 2006. (Logo: ) The Company reported a net loss for the second quarter of 2006 of ($6.0 million), or ($0.09) per share. This compares with a net loss of ($4.3 million), or ($0.09) per share, for the same period last year. EntreMed's reported net loss for the first six months of 2006 was ($40.7 million), or ($0.59) per share as compared to ($9.8 million) or ($0.22) per share for 2005. The 2006 net loss for the six month period includes a non- cash charge of $29.5 million resulting from the acquisition of Miikana Therapeutics in January 2006. Excluding this non-cash charge, the Company's net loss for the first six months of 2006 was ($11.2 million), compared with ($9.8 million) for the first six months of 2005. The Company did not report any revenues for the first six months of 2006 versus $605,000 for the comparable period in 2005, although the Company believes that it will record royalty revenue on sales of Thalomid(R) by Celgene in the third and fourth quarters of 2006. As of June 30, 2006, EntreMed had cash and short-term investments of approximately $45.1 million. Dane Saglio, EntreMed Chief Financial Officer, commented on the results for the second quarter, "The Company's second quarter loss was slightly less than projected due primarily to the timing of our contract manufacturing activities. R&D expenditures will increase in the second half of the year as we secure material to support on-going and planned trials for our three clinical-stage drug candidates. As in 2005, we anticipate beginning to record royalty revenue on Celgene's sales of Thalomid(R) in the third quarter and believe that 2006 royalty revenue will be in line with 2005." James S. Burns, EntreMed President and Chief Executive Officer, commented, "Our progress for the first half of 2006 is consistent with both our guidance and my expectations. R&D expenses are in line with our progress on Panzem(R) NCD, MKC-1, ENMD-1198 and our key preclinical programs. Consistent with our previous guidance, we anticipate achieving our planned milestones and remaining on our expense budget for the remainder of 2006." The second quarter update call is scheduled for Tuesday, August 15, 2006 from 10:00 am to 11:00 am ET and will include a question and answer session. To access the live conference, please dial 888-603-6873 (U.S. or Canada) or 973-582-2706 (internationally) and reference conference number 7678866 at least 10 minutes prior to the beginning of the call. A digital recording will be available approximately one hour after completion of the conference and will be accessible for 60 days. To access the recording, dial 877-519-4471 (U.S. or Canada) or 973-341-3080 (internationally) and enter the digital pin number 7678866. This call will not be web cast; however, an audio replay will also be available on the Company's website at approximately one hour after the conclusion of the live conference. About EntreMed EntreMed, Inc. is a clinical-stage pharmaceutical company developing therapeutic candidates primarily for the treatment of cancer and inflammation. Panzem(R) (2-methoxyestradiol or 2ME2), the Company's lead drug candidate, is currently in Phase 2 clinical trials for cancer, as well as in preclinical development for rheumatoid arthritis. MKC-1, an oral cell cycle regulator, is in Phase 2 studies for metastatic breast cancer. ENMD-1198, a novel tubulin binding agent, is also in Phase 1 studies in advanced cancers. EntreMed's goal is to develop and commercialize new compounds based on the Company's expertise in angiogenesis, cell cycle regulation and inflammation -- processes vital to the treatment of cancer and other diseases, such as rheumatoid arthritis. Additional information about EntreMed is available on the Company's website at and in various filings with the Securities and Exchange Commission. Forward Looking Statements This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act with respect to the outlook for expectations for future financial or business performance (including the timing of royalty revenues and future R&D expenditures), strategies, expectations and goals. Forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Forward-looking statements speak only as of the date they are made, and no duty to update forward-looking statements is assumed. Actual results could differ materially from those currently anticipated due to a number of factors, including those set forth in Securities and Exchange Commission filings under "Risk Factors," including risks relating to the need for additional capital and the uncertainty of additional funding; variations in actual sales of Thalomid(R), risks associated with the integration of Miikana and its product candidates; the early-stage products under development; results in preclinical models are not necessarily indicative of clinical results, uncertainties relating to preclinical and clinical trials; success in the clinical development of any products; dependence on third parties; future capital needs; and risks relating to the commercialization, if any, of the Company's proposed products (such as marketing, safety, regulatory, patent, product liability, supply, competition and other risks). (Financial Table Attached) ENTREMED, INC. SUMMARY OF OPERATING RESULTS Three Months Ended June 30, 2006 2005 Total revenues $ 0 $ 579,461 Research and development 4,258,206 3,812,353 General and administrative 1,942,652 1,339,150 Acquired in-process research and development 353,833 0 Net loss (6,025,724) (4,300,210) Net loss per share (basic and diluted) attributable to common shareholders $ (0.09) $ (0.09) Weighted average number of shares outstanding (basic and diluted) 73,194,814 49,819,569 Six Months Ended June 30, 2006 2005 Total revenues $ 0 $ 604,710 Research and development 8,269,306 8,191,709 General and administrative 3,759,346 2,599,972 Acquired in-process research and development 29,481,894 0 Net loss (40,736,427) (9,756,678) Net loss per share (basic and diluted) attributable to common shareholders $ (0.59) $ (0.22) Weighted average number of shares outstanding (basic and diluted) 69,765,434 46,324,989 Cash and short-term investments $ 45,091,175 $43,589,889 CONTACT: Ginny Dunn, Associate Director, Corporate Communications & Investor Relations, of EntreMed, Inc., +1-240-864-2643. Photo: NewsCom: AP Archive: PRN Photo Desk, photodesk@prnewswire.comEntreMed, Inc. CONTACT: Ginny Dunn, Associate Director, Corporate Communications &Investor Relations, of EntreMed, Inc., +1-240-864-2643 Web site:

Acquisition

100 Deals associated with MKC-1

External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Endometrial Carcinoma	Phase 2	CA	CASI Pharmaceuticals, Inc.	01 Jan 2008
Recurrent ovarian cancer	Phase 2	CA	CASI Pharmaceuticals, Inc.	01 Jan 2008
Pancreatic carcinoma non-resectable	Phase 2	US	CASI Pharmaceuticals, Inc.	01 Nov 2007
Advanced cancer	Phase 2	US	CASI Pharmaceuticals, Inc.	01 Oct 2006
Non-Small Cell Lung Cancer	Phase 2	US	CASI Pharmaceuticals, Inc.	01 Oct 2006
Advanced breast cancer	Phase 2	US	CASI Pharmaceuticals, Inc.	01 Jan 2006
Metastatic breast cancer	Phase 2	US	CASI Pharmaceuticals, Inc.	01 Jan 2006

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00568646 (Pubmed \| Invest New Drugs)	Phase 2	Pancreatic carcinoma non-resectable	20	MKC-1	fylvhmhwta(alkuegetzp) = grade 3 and 4 hmavxukcqc (dvucvbijsb ) View more	Negative	01 Aug 2012
ASCO2009	Phase 1/2	Non-Small Cell Lung Cancer Second line	27	MKC-1	utltiohqcq(vddujthppl) = gjxzhvnxxn wgcxyzivqt (fpxkufoyts ) View more	-	20 May 2009
ASCO2008	Phase 2	Metastatic breast cancer	58	MKC-1	ksptccuhuw(akoxkaupbf) = amdtrkdquw nfuknuafaj (mmopcexggu )	-	20 May 2008
ASCO2008	Phase 1/2	Advanced Lung Non-Small Cell Carcinoma Maintenance	19	MKC-1	cdquuyuzsb(ctynxeeskb) = srjrftqwif ybvfuboksm (qdbogevvoa )	-	20 May 2008
ASCO2008	Phase 1/2	Advanced Lung Non-Small Cell Carcinoma Maintenance	19	Pemetrexed	cdquuyuzsb(ctynxeeskb) = gamnepwkra ybvfuboksm (qdbogevvoa )	-	20 May 2008

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