Denibulin HCl

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

Description:Denibulin (MN-029) is a novel vascular-disrupting agent that reversibly inhibits microtubule assembly, resulting in disruption of the cytoskeleton of tumor vascular endothelial cells. The results of preclinical study demonstrated that MN-029 could cause rapid vascular shutdown in solid tumors, dose-dependent secondary tumor cell killing, and effective enhancement of the antitumor effects of radiation and cisplatin chemotherapy.

Price and Availability

Denibulin 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#: 206224Name: Denibulin HClCAS#: 779356-64-8 (HCl)Chemical Formula: C18H20ClN5O3S Exact Mass: Molecular Weight: 421.9Elemental Analysis: C, 51.24; H, 4.78; Cl, 8.40; N, 16.60; O, 11.38; S, 7.60

Related CAS #:284019-34-7 (free base)779356-64-8 (HCl)

Synonym:MN029; MN-029; MN 029; Denibulin

IUPAC/Chemical Name:Methyl [5-[[4-[[(2S)-2-aminopropanoyl]amino]phenyl]sulfanyl]-1H-benzimidazol-2-yl]carbamate monohydrochloride

InChi Key:JUMSCXLBFWHCRA-PPHPATTJSA-N

InChi Code:InChI=1S/C18H19N5O3S.ClH/c1-10(19)16(24)20-11-3-5-12(6-4-11)27-13-7-8-14-15(9-13)22-17(21-14)23-18(25)26-2;/h3-10H,19H2,1-2H3,(H,20,24)(H2,21,22,23,25);1H/t10-;/m0./s1

SMILES Code:O=C(OC)NC1=NC2=CC(SC3=CC=C(NC([C@@H](N)C)=O)C=C3)=CC=C2N1.[H]Cl

Technical Data

Additional Information

MN-029 is a novel VDA that binds reversibly to the colchicine-binding site on tubulin and inhibits microtubule assembly, resulting in disruption of the cytoskeleton of tumor endothelial cells (EC). Disruption of the tumor EC cytoskeleton ultimately leads to a temporary reduction in tumor blood flow. MN-029 is a novel, small molecule VDA being developed for the treatment of solid tumors. Medicinova licensed MN-029 from Angiogene Pharmaceuticals, Ltd. Several preclinical pharmacology studies conducted by Angiogene Pharmaceuticals and us have assessed the mechanism of action and anti-tumor activity of MN-029 in vivo in rodent models of breast adenocarcinoma, colon carcinoma, lung carcinoma and KHT sarcoma. In these studies, MN-029 damaged poorly formed tumor blood vessels by weakening tumor blood vessel walls and causing leakage, clotting and eventual vascular shutdown within the tumor. These studies suggest that MN-029 acts quickly and is rapidly cleared from the body, which may reduce the potential for some adverse effects commonly associated with chemotherapy. Shutdown of tumor blood flow in tumor models was confirmed through the use of dynamic contrast-enhanced MRI.  See Medicinova"s website.  

References

1. Traynor, Anne M.; Gordon, Michael S.; Alberti,Dona; Mendelson, David S.; Munsey, Mark S.; Wilding, George; Gammans,Richard E.; Read, William L. A dose escalation, safety, and tolerabilitystudy of MN-029 in patients with advanced solid tumors. InvestigationalNew Drugs (2010), 28(4), 509-515. CODEN: INNDDK ISSN:0167-6997. AN2010:638288

2. Lee, Ray M.; Gewirtz, David A. Colchicine site inhibitors ofmicrotubule integrity as vascular disrupting agents. Drug DevelopmentResearch (2008), 69(6), 352-358. CODEN: DDREDK ISSN:0272-4391. CAN150:229065 AN 2009:13930

3. Cai, Sui X. Small molecule vascular disrupting agents: potential newdrugs for cancer treatment. Recent Patents on Anti-Cancer Drug Discovery(2007), 2(1), 79-101. CODEN: RPADDY ISSN:1574-8928. CAN 146:414035 AN2007:141194

4. Shi, Wenyin; Siemann, Dietmar W. Preclinical studies of the novelvascular disrupting agent MN-029. Anticancer Research (2005), 25(6B),3899-3904. CODEN: ANTRD4 ISSN:0250-7005. CAN 144:285716 AN 2005:1291495

5. Ryan, Anderson Joseph. Vascular damaging agents, such as ZD6126 foradministration as an intravenous infusion for treatment of solid tumors.PCT Int. Appl. (2005), 26 pp. CODEN: PIXXD2 WO 2005110426 A1 20051124CAN 143:483170 AN 2005:1242338

6. Traynor Anne M; Gordon Michael S; Alberti Dona; Mendelson David S;Munsey Mark S; Wilding George; Gammans Richard E; Read William L A doseescalation, safety, and tolerability study of MN-029 in patients withadvanced solid tumors. Investigational new drugs (2010), 28(4), 509-15.

7. Cai Sui X Small molecule vascular disrupting agents: potential newdrugs for cancer treatment. Recent patents on anti-cancer drug discovery(2007), 2(1), 79-101.

8. Shi Wenyin; Siemann Dietmar W Preclinical studies of the novelvascular disrupting agent MN-029. Anticancer research (2005), 25(6B),3899-904.