WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200831
CAS#: 1000852-17-4
Description: Crolibulin, also known as EPC2407 and crinobulin, is a small molecule tubulin polymerization inhibitor with potential antineoplastic activity. Microtubulin inhibitor EPC2407 binds to the colchicine-binding site on beta-tubulin and inhibits the polymerization of tubulin into microtubules, which may result in cell cycle arrest, the induction of apoptosis, and the inhibition of tumor cell proliferation. As a vascular disruption agent (VDA), this agent also disrupts tumor neovascularization, which may result in a reduction in tumor blood flow and tumor hypoxia and ischemic necrosis.
MedKoo Cat#: 200831
Name: Crolibulin
CAS#: 1000852-17-4
Chemical Formula: C18H17BrN4O3
Exact Mass: 416.0484
Molecular Weight: 417.26
Elemental Analysis: C, 51.81; H, 4.11; Br, 19.15; N, 13.43; O, 11.50
Synonym: EPC2407; EPC 2407; EPC-2407; Crolibulin crinobulin.
IUPAC/Chemical Name: (R)-2,7,8-triamino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene-3-carbonitrile
InChi Key: JXONINOYTKKXQQ-CQSZACIVSA-N
InChi Code: InChI=1S/C18H17BrN4O3/c1-24-13-6-8(5-11(19)17(13)25-2)14-9-3-4-12(21)15(22)16(9)26-18(23)10(14)7-20/h3-6,14H,21-23H2,1-2H3/t14-/m1/s1
SMILES Code: N#CC1=C(N)OC2=C(C=CC(N)=C2N)[C@H]1C3=CC(OC)=C(OC)C(Br)=C3
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
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).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 417.26 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: Zhang Z, Wang C, Ma L, Jiang X, Wu C, Wang Y, Jiang Y, Zheng W, Yang Y, Ma Y, Yang J. Molecular mechanism of crolibulin in complex with tubulin provides a rationale for drug design. Biochem Biophys Res Commun. 2019 Apr 2;511(2):381-386. doi: 10.1016/j.bbrc.2019.02.064. Epub 2019 Feb 22. PMID: 30803758.
2: Lorza AMA, Ravi H, Philip RC, Galons JP, Trouard TP, Parra NA, Von Hoff DD, Read WL, Tibes R, Korn RL, Raghunand N. Dose-response assessment by quantitative MRI in a phase 1 clinical study of the anti-cancer vascular disrupting agent crolibulin. Sci Rep. 2020 Sep 2;10(1):14449. doi: 10.1038/s41598-020-71246-w. PMID: 32879326; PMCID: PMC7468301.
3: Mirzaei H, Shokrzadeh M, Modanloo M, Ziar A, Riazi GH, Emami S. New indole- based chalconoids as tubulin-targeting antiproliferative agents. Bioorg Chem. 2017 Dec;75:86-98. doi: 10.1016/j.bioorg.2017.09.005. Epub 2017 Sep 7. PMID: 28922629.
4: Liu Y, Yang D, Hong Z, Guo S, Liu M, Zuo D, Ge D, Qin M, Sun D. Synthesis and biological evaluation of 4,6-diphenyl-2-(1H-pyrrol-1-yl)nicotinonitrile analogues of crolibulin and combretastatin A-4. Eur J Med Chem. 2018 Feb 25;146:185-193. doi: 10.1016/j.ejmech.2018.01.052. Epub 2018 Feb 4. PMID: 29407949.
5: Patil SA, Patil R, Pfeffer LM, Miller DD. Chromenes: potential new chemotherapeutic agents for cancer. Future Med Chem. 2013 Sep;5(14):1647-60. doi: 10.4155/fmc.13.126. PMID: 24047270.
6: Liu J, Zuo D, Jing T, Guo M, Xing L, Zhang W, Zhao J, Shen J, Gong P, Zhang D, Zhai X. Synthesis, biological evaluation and molecular modeling of imidazo[1,2-a]pyridine derivatives as potent antitubulin agents. Bioorg Med Chem. 2017 Aug 1;25(15):4088-4099. doi: 10.1016/j.bmc.2017.05.057. Epub 2017 May 30. PMID: 28622907.
7: Folaron M, Seshadri M. Bioluminescence and MR Imaging of the Safety and Efficacy of Vascular Disruption in Gliomas. Mol Imaging Biol. 2016 Dec;18(6):860-869. doi: 10.1007/s11307-016-0963-8. PMID: 27160251.
8: Zhai X, Wang X, Wang J, Liu J, Zuo D, Jiang N, Zeng T, Yang X, Jing T, Gong P. Discovery and Optimization of Novel 5-Indolyl-7-arylimidazo[1,2-a]pyridine-8-carbonitrile Derivatives as Potent Antitubulin Agents Targeting Colchicine-binding Site. Sci Rep. 2017 Feb 27;7:43398. doi: 10.1038/srep43398. PMID: 28240326; PMCID: PMC5327470.
9: Kalmuk J, Folaron M, Buchinger J, Pili R, Seshadri M. Multimodal imaging guided preclinical trials of vascular targeting in prostate cancer. Oncotarget. 2015 Sep 15;6(27):24376-92. doi: 10.18632/oncotarget.4463. PMID: 26203773; PMCID: PMC4695192.
10: Cai SX, Drewe J, Kemnitzer W. Discovery of 4-aryl-4H-chromenes as potent apoptosis inducers using a cell- and caspase-based Anti-cancer Screening Apoptosis Program (ASAP): SAR studies and the identification of novel vascular disrupting agents. Anticancer Agents Med Chem. 2009 May;9(4):437-56. doi: 10.2174/1871520610909040437. PMID: 19442043.
11: Rich LJ, Seshadri M. Photoacoustic imaging of vascular hemodynamics: validation with blood oxygenation level-dependent MR imaging. Radiology. 2015 Apr;275(1):110-8. doi: 10.1148/radiol.14140654. Epub 2014 Nov 20. PMID: 25423146; PMCID: PMC4455674.
