ENMD-1198

WARNING: This product is for research use only, not for human or veterinary use.

Description:ENMD-1198 is a potent, orally-active, antimitotic agent that induces cell cycle arrest and apoptosis in tumor cells. ENMD-1198 has shown pronounced antitumor activity as well as substantial synergistic effects in combination with standard of care chemotherapeutic agents in numerous preclinical models. ENMD-1198 does not exhibit sensitivity to multi-drug resistance mechanisms in preclinical studies. ENMD-1198 also has shown preclinical activity towards taxane and vinca alkaloid resistant tumor cells. Additionally, ENMD-1198 decreases the activity of three oncogenic proteins (HIF-1α, NF-κB and STAT3) that are known to promote tumor growth and progression. ENMD-1198 has been evaluated in a Phase 1 clinical trial for safety, tolerability, pharmacokinetics, and clinical benefit in advanced cancer patients. (Source: http://www.entremed.com/science/enmd-1198/).

Price and Availability

ENMD-1198 is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 201260Name: ENMD-1198CAS#: 864668-87-1Chemical Formula: C20H25NO2Exact Mass: 311.18853Molecular Weight: 311.42Elemental Analysis:C, 77.14; H, 8.09; N, 4.50; O, 10.28

Synonym:ENMD 1198; ENMD1198; ENMD 1198; IRC 110160; RC-110160; RC110160

IUPAC/Chemical Name:(13R)-2-methoxy-13-methyl-7,8,9,11,12,13,14,15-octahydro-6H-cyclopenta[a]phenanthrene-3-carboxamide

InChi Key:YQJWOUQGXATDAE-CBTMWXCYSA-N

InChi Code:InChI=1S/C20H25NO2/c1-20-8-3-4-17(20)14-6-5-12-10-16(19(21)22)18(23-2)11-15(12)13(14)7-9-20/h3,8,10-11,13-14,17H,4-7,9H2,1-2H3,(H2,21,22)/t13?,14?,17?,20-/m0/s1

SMILES Code:O=C(C1=C(OC)C=C2C3CC[C@]4(C)C=CCC4C3CCC2=C1)N

Technical Data

Additional Information

ENMD-1198 is a new chemical entity (NCE) based on a modified chemical structure of 2ME2 designed to increase antitumor and antiangiogenic properties and improve metabolism. ENMD-1198 is characterized by its multiple mechanisms of action, which include inducing apoptosis, binding microtubules, and inhibiting HIF-1alpha. HIF-1alpha is over-expressed in more than 70% of human tumors and its over-expression correlates with tumor aggressiveness, metastases and poor prognosis. Preclinical studies identified ENMD-1198 as an orally active, microtubule disrupting agent that leads to arrest of cell division and apoptosis in tumor cells. Additionally, ENMD-1198 exerts antiangiogenic activity that contributes to its overall antitumor effects. In preclinical studies, ENMD-1198 has demonstrated pronounced in vivo antitumor activity in models of human cancer. Oral daily treatment with ENMD- 1198 in an orthotopic MDA MB 231 breast cancer model led to a reduction in tumor burden equivalent to the positive control cyclophosphamide, disruption of microtubules within tumor cells, and a substantial decrease in HIF-1alpha. ENMD-1198 also reduced protein levels for two additional transcription factors, NFkB and Stat3, known to modulate HIF-1alpha protein levels in vitro. All three transcription factors are known to regulate multiple genes and their proteins that contribute to tumor growth and progression. In preclinical tumor studies, serum proteins regulated by HIF-1alpha, NFkB and Stat3, were also reduced substantially following oral administration of ENMD-1198. Results from several studies demonstrate significantly (40-100%) decreased plasma or serum levels of human VEGF (secreted by tumor cells), a major proangiogenic growth factor, compared to control animals following therapy with ENMD-1198. Serum levels of human IL-6 were also decreased significantly (62-96%). Over-expression of IL-6 is associated with higher morbidity in breast cancers, bone metastases, increased aromatase synthesis, and increased cancer drug resistance. Tumor levels of a third tumor protein regulated by HIF-1alpha, carbonic anhydrase IX (CA IX), were also decreased, consistent with HIF-1alpha inhibition. (source: biospace.com)   

References

1: Pasquier E, Sinnappan S, Munoz MA, Kavallaris M.ENMD-1198, a new analogue of 2-methoxyestradiol, displays bothantiangiogenic and vascular-disrupting properties. Mol Cancer Ther. 2010May;9(5):1408-18. Epub 2010 May 4. PubMed PMID: 20442304.

2: Zhou Q, Gustafson D, Nallapareddy S, Diab S, Leong S, Lewis K, GoreL, Messersmith WA, Treston AM, Eckhardt SG, Sidor C, Camidge DR. A phaseI dose-escalation, safety and pharmacokinetic study of the2-methoxyestradiol analog ENMD-1198 administered orally to patients withadvanced cancer. Invest New Drugs. 2010 Jan 19. [Epub ahead of print]PubMed PMID: 20084425.

3: Agoston GE, Shah JH, Suwandi L, Hanson AD, Zhan X, LaVallee TM,Pribluda V, Treston AM. Synthesis, antiproliferative, andpharmacokinetic properties of 3- and 17-double-modified analogs of2-methoxyestradiol. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6241-4. Epub2009 Aug 8. PubMed PMID: 19782564.

4: Moser C, Lang SA, Mori A, Hellerbrand C, Schlitt HJ, Geissler EK,Fogler WE, Stoeltzing O. ENMD-1198, a novel tubulin-binding agentreduces HIF-1alpha and STAT3 activity in human hepatocellularcarcinoma(HCC) cells, and inhibits growth and vascularization in vivo.BMC Cancer. 2008 Jul 23;8:206. PubMed PMID: 18651980; PubMed CentralPMCID: PMC2496914.

5: Foster PA, Stengel C, Ali T, Leese MP, Potter BV, Reed MJ, Purohit A,Newman SP. A comparison of two orally bioavailable anti-cancer agents,IRC-110160 and STX140. Anticancer Res. 2008 May-Jun;28(3A):1483-91.PubMed PMID: 18630502.

6: LaVallee TM, Burke PA, Swartz GM, Hamel E, Agoston GE, Shah J,Suwandi L, Hanson AD, Fogler WE, Sidor CF, Treston AM. Significantantitumor activity in vivo following treatment with the microtubuleagent ENMD-1198. Mol Cancer Ther. 2008 Jun;7(6):1472-82. PubMed PMID:18566218.