ABT-751 | CAS#857447-92-8 | 141430-65-1 | antimitotic agent

MedKoo Cat#: 200050 | Name: ABT-751

Description:

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

ABT-751, also known as E7010, is an orally bioavailable antimitotic sulfonamide. ABT-751 binds to the colchicine-binding site on beta-tubulin and inhibits the polymerization of microtubules, thereby preventing tumor cell replication. This agent also disrupts tumor neovascularization, reducing tumor blood flow and so inducing a cytotoxic effect.

Chemical Structure

ABT-751

CAS#141430-65-1 (free base)

Theoretical Analysis

MedKoo Cat#: 200050

Name: ABT-751

CAS#: 141430-65-1 (free base)

Chemical Formula: C18H17N3O4S

Exact Mass: 371.0940

Molecular Weight: 371.41

Elemental Analysis: C, 58.21; H, 4.61; N, 11.31; O, 17.23; S, 8.63

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 220.00	Ready to ship
50mg	USD 350.00	Ready to ship
100mg	USD 650.00	Ready to ship
200mg	USD 1,050.00	Ready to ship

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Related CAS #

141430-65-1 (free base) 857447-92-8 141450-48-8 (HCl)

Synonym

ABT751; ABT-751; ABT 751; E 7010; E-7010; E7010

IUPAC/Chemical Name

N-(2-((4-hydroxyphenyl)amino)pyridin-3-yl)-4-methoxybenzenesulfonamide

InChi Key

URCVCIZFVQDVPM-UHFFFAOYSA-N

InChi Code

InChI=1S/C18H17N3O4S/c1-25-15-8-10-16(11-9-15)26(23,24)21-17-3-2-12-19-18(17)20-13-4-6-14(22)7-5-13/h2-12,21-22H,1H3,(H,19,20)

SMILES Code

O=S(C1=CC=C(OC)C=C1)(NC2=CC=CN=C2NC3=CC=C(O)C=C3)=O

Appearance

Pink Solid

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

2935009090

More Info

Related CAS# 141430-65-1 (ABT-751) 857447-92-8 (previous assigned for ABT-751 's CAS#, it was deleted now)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A20T09K22

View CoA: current batch, Lot#C8R12B19

QC Data

View QC data: current batch, Lot#C8R12B19

View QC data: current batch, Lot#A20T09K22

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

ABT-751 (E7010) is a tubulin-binding and antimitotic sulfonamide agent with IC50s of ~ 1.5 and 3.4 μM in neuroblastoma and non-neuroblastoma cell lines, respectively.

In vitro activity:

The upstream mechanisms of apoptosis which were triggered by a novel anti-microtubule drug, ABT-751, were investigated in hepatocellular carcinoma-derived Huh-7 cells. ABT-751 caused dysregulation of microtubule, collapse of mitochondrial membrane potential, generation of reactive oxygen species (ROS), DNA damage, G2/M cell cycle arrest, inhibition of anchorage-independent cell growth and apoptosis in Huh-7 cells. ABT-751 also induced early autophagy via upregulation of nuclear TP53 and downregulation of the AKT serine/threonine kinase (AKT)/mechanistic target of rapamycin (MTOR) pathway. Through modulation of the expression levels of DNA damage checkpoint proteins and G2/M cell cycle regulators, ABT-751 induced G2/M cell cycle arrest. Subsequently, ABT-751 triggered apoptosis with marked downregulation of B-cell CLL/lymphoma 2, upregulation of mitochondrial BCL2 antagonist/killer 1 and BCL2 like 11 protein levels, and cleavages of caspase 8 (CASP8), CASP9, CASP3 and DNA fragmentation factor subunit alpha proteins. Reference: Toxicol Appl Pharmacol. 2016 Nov 15;311:88-98. https://www.sciencedirect.com/science/article/abs/pii/S0041008X16302873?via%3Dihub

In vivo activity:

The antivascular properties of ABT-751 were investigated in a rat subcutaneous tumor model using dynamic contrast-enhanced magnetic resonance imaging. A single dose of ABT-751 (30 mg/kg, intravenously) induced a rapid, transient reduction in tumor perfusion. After 1 h, tumor perfusion decreased by 57% before recovering to near pretreatment levels within 6 h. In contrast, ABT-751 produced little change in muscle perfusion at either time point. Reference: Anticancer Drugs. 2009 Jul;20(6):483-92. https://journals.lww.com/anti-cancerdrugs/Abstract/2009/07000/ABT_751,_a_novel_tubulin_binding_agent,_decreases.10.aspx

	Solvent	mg/mL	mM
Solubility
	DMSO	53.1	142.83
	Ethanol	10.7	28.67

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 371.41 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

Formulation protocol:

1. Wei RJ, Lin SS, Wu WR, Chen LR, Li CF, Chen HD, Chou CT, Chen YC, Liang SS, Chien ST, Shiue YL. A microtubule inhibitor, ABT-751, induces autophagy and delays apoptosis in Huh-7 cells. Toxicol Appl Pharmacol. 2016 Nov 15;311:88-98. doi: 10.1016/j.taap.2016.09.021. Epub 2016 Sep 24. PMID: 27678524. 2. Dehghanian SZ, Pan CT, Lee JM, Shiue YL. ABT-751 Induces Multiple Anticancer Effects in Urinary Bladder Urothelial Carcinoma-Derived Cells: Highlighting the Induction of Cytostasis through the Inhibition of SKP2 at Both Transcriptional and Post-Translational Levels. Int J Mol Sci. 2021 Jan 19;22(2):945. doi: 10.3390/ijms22020945. PMID: 33478005; PMCID: PMC7835924. 3. Luo Y, Hradil VP, Frost DJ, Rosenberg SH, Gordon GB, Morgan SJ, Gagne GD, Cox BF, Tahir SK, Fox GB. ABT-751, a novel tubulin-binding agent, decreases tumor perfusion and disrupts tumor vasculature. Anticancer Drugs. 2009 Jul;20(6):483-92. doi: 10.1097/CAD.0b013e32832c0acf. PMID: 19398903.

In vitro protocol:

In vivo protocol:

1. Luo Y, Hradil VP, Frost DJ, Rosenberg SH, Gordon GB, Morgan SJ, Gagne GD, Cox BF, Tahir SK, Fox GB. ABT-751, a novel tubulin-binding agent, decreases tumor perfusion and disrupts tumor vasculature. Anticancer Drugs. 2009 Jul;20(6):483-92. doi: 10.1097/CAD.0b013e32832c0acf. PMID: 19398903.

1: Galmarini CM. ABT-751 (Abbott). Curr Opin Investig Drugs. 2005 Jun;6(6):623-30. PMID: 15988914. 2: Dehghanian SZ, Pan CT, Lee JM, Shiue YL. ABT-751 Induces Multiple Anticancer Effects in Urinary Bladder Urothelial Carcinoma-Derived Cells: Highlighting the Induction of Cytostasis through the Inhibition of SKP2 at Both Transcriptional and Post-Translational Levels. Int J Mol Sci. 2021 Jan 19;22(2):945. doi: 10.3390/ijms22020945. PMID: 33478005; PMCID: PMC7835924. 3: Luo Y, Hradil VP, Frost DJ, Rosenberg SH, Gordon GB, Morgan SJ, Gagne GD, Cox BF, Tahir SK, Fox GB. ABT-751, a novel tubulin-binding agent, decreases tumor perfusion and disrupts tumor vasculature. Anticancer Drugs. 2009 Jul;20(6):483-92. doi: 10.1097/CAD.0b013e32832c0acf. PMID: 19398903. 4: Gaynon PS, Harned TM; Therapeutic Advances in Childhood Leukemia/Lymphoma Consortium. ABT-751 in relapsed childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2012 Oct;34(7):583-4. doi: 10.1097/MPH.0b013e3182532446. PMID: 22584778. 5: Wei RJ, Lin SS, Wu WR, Chen LR, Li CF, Chen HD, Chou CT, Chen YC, Liang SS, Chien ST, Shiue YL. A microtubule inhibitor, ABT-751, induces autophagy and delays apoptosis in Huh-7 cells. Toxicol Appl Pharmacol. 2016 Nov 15;311:88-98. doi: 10.1016/j.taap.2016.09.021. Epub 2016 Sep 24. PMID: 27678524. 6: Meany HJ, Sackett DL, Maris JM, Ward Y, Krivoshik A, Cohn SL, Steinberg SM, Balis FM, Fox E. Clinical outcome in children with recurrent neuroblastoma treated with ABT-751 and effect of ABT-751 on proliferation of neuroblastoma cell lines and on tubulin polymerization in vitro. Pediatr Blood Cancer. 2010 Jan;54(1):47-54. doi: 10.1002/pbc.22267. PMID: 19731320; PMCID: PMC2783914. 7: Rudek MA, Zhao M, He P, Messersmith WA, Baker SD. Validation and implementation of a liquid chromatography/tandem mass spectrometry assay to quantitate ABT-751, ABT-751 glucuronide, and ABT-751 sulfate in human plasma for clinical pharmacology studies. J Pharm Biomed Anal. 2006 Sep 18;42(2):253-60. doi: 10.1016/j.jpba.2006.04.010. Epub 2006 Jun 9. PMID: 16765012. 8: Wei RJ, Wu WR, Pan CT, Yu CY, Li CF, Chen LR, Liang SS, Shiue YL. Inhibition of the formation of autophagosome but not autolysosome augments ABT-751-induced apoptosis in TP53-deficient Hep-3B cells. J Cell Physiol. 2019 Jun;234(6):9551-9563. doi: 10.1002/jcp.27643. Epub 2018 Oct 26. PMID: 30367486. 9: Morton CL, Favours EG, Mercer KS, Boltz CR, Crumpton JC, Tucker C, Billups CA, Houghton PJ. Evaluation of ABT-751 against childhood cancer models in vivo. Invest New Drugs. 2007 Aug;25(4):285-95. doi: 10.1007/s10637-007-9042-y. Epub 2007 Mar 24. PMID: 17384918. 10: Rudek MA, Dasari A, Laheru D, He P, Jin R, Walker R, Taylor GE, Jimeno A, Donehower RC, Hidalgo M, Messersmith WA, Purcell WT. Phase 1 Study of ABT-751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer. J Clin Pharmacol. 2016 Aug;56(8):966-73. doi: 10.1002/jcph.681. Epub 2016 Feb 2. PMID: 26632033; PMCID: PMC4892995. 11: Hande KR, Hagey A, Berlin J, Cai Y, Meek K, Kobayashi H, Lockhart AC, Medina D, Sosman J, Gordon GB, Rothenberg ML. The pharmacokinetics and safety of ABT-751, a novel, orally bioavailable sulfonamide antimitotic agent: results of a phase 1 study. Clin Cancer Res. 2006 May 1;12(9):2834-40. doi: 10.1158/1078-0432.CCR-05-2159. PMID: 16675578. 12: Silver M, Rusk A, Phillips B, Beck E, Jankowski M, Philibert J, Hahn K, Hershey E, McKeegan E, Bauch J, Krivoshik A, Khanna C. Evaluation of the oral antimitotic agent (ABT-751) in dogs with lymphoma. J Vet Intern Med. 2012 Mar- Apr;26(2):349-54. doi: 10.1111/j.1939-1676.2012.00892.x. Epub 2012 Feb 28. PMID: 22369215. 13: Wang X, Lu Y, Sun D, Qian J, Tu S, Yue W, Lin H, Tang H, Meng F, He Q, Xie Z, Zhang Y, Chen H, Ma S, Zuo Z, Ye F. Discovery of 4-methoxy-N-(1-naphthyl)benzenesulfonamide derivatives as small molecule dual- target inhibitors of tubulin and signal transducer and activator of transcription 3 (STAT3) based on ABT-751. Bioorg Chem. 2022 Aug;125:105864. doi: 10.1016/j.bioorg.2022.105864. Epub 2022 May 10. PMID: 35584606. 14: Fox E, Maris JM, Cohn SL, Goodspeed W, Goodwin A, Kromplewski M, Medina D, Xiong H, Krivoshik A, Widemann B, Adamson PC, Balis FM. Pharmacokinetics of orally administered ABT-751 in children with neuroblastoma and other solid tumors. Cancer Chemother Pharmacol. 2010 Sep;66(4):737-43. doi: 10.1007/s00280-009-1218-z. Epub 2010 Jan 1. PMID: 20044751; PMCID: PMC6936731. 15: Fox E, Maris JM, Widemann BC, Goodspeed W, Goodwin A, Kromplewski M, Fouts ME, Medina D, Cohn SL, Krivoshik A, Hagey AE, Adamson PC, Balis FM. A phase I study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 21 days every 28 days in pediatric patients with solid tumors. Clin Cancer Res. 2008 Feb 15;14(4):1111-5. doi: 10.1158/1078-0432.CCR-07-4097. PMID: 18281544. 16: Mauer AM, Cohen EE, Ma PC, Kozloff MF, Schwartzberg L, Coates AI, Qian J, Hagey AE, Gordon GB. A phase II study of ABT-751 in patients with advanced non- small cell lung cancer. J Thorac Oncol. 2008 Jun;3(6):631-6. doi: 10.1097/JTO.0b013e318174e01f. PMID: 18520803. 17: Rudin CM, Mauer A, Smakal M, Juergens R, Spelda S, Wertheim M, Coates A, McKeegan E, Ansell P, Zhou X, Qian J, Pradhan R, Dowell B, Krivoshik A, Gordon G. Phase I/II study of pemetrexed with or without ABT-751 in advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2011 Mar 10;29(8):1075-82. doi: 10.1200/JCO.2010.32.5944. Epub 2011 Feb 7. PMID: 21300929; PMCID: PMC4672026. 18: Chen NE, Maldonado NV, Khankaldyyan V, Shimada H, Song MM, Maurer BJ, Reynolds CP. Reactive Oxygen Species Mediates the Synergistic Activity of Fenretinide Combined with the Microtubule Inhibitor ABT-751 against Multidrug- Resistant Recurrent Neuroblastoma Xenografts. Mol Cancer Ther. 2016 Nov;15(11):2653-2664. doi: 10.1158/1535-7163.MCT-16-0156. Epub 2016 Aug 16. PMID: 27530131. 19: Michels J, Ellard SL, Le L, Kollmannsberger C, Murray N, Tomlinson Guns ES, Carr R, Chi KN. A phase IB study of ABT-751 in combination with docetaxel in patients with advanced castration-resistant prostate cancer. Ann Oncol. 2010 Feb;21(2):305-311. doi: 10.1093/annonc/mdp311. Epub 2009 Jul 24. PMID: 19633045. 20: Innocenti F, Ramírez J, Obel J, Xiong J, Mirkov S, Chiu YL, Katz DA, Carr RA, Zhang W, Das S, Adjei A, Moyer AM, Chen PX, Krivoshik A, Medina D, Gordon GB, Ratain MJ, Sahelijo L, Weinshilboum RM, Fleming GF, Bhathena A. Preclinical discovery of candidate genes to guide pharmacogenetics during phase I development: the example of the novel anticancer agent ABT-751. Pharmacogenet Genomics. 2013 Jul;23(7):374-81. doi: 10.1097/FPC.0b013e3283623e81. PMID: 23670235; PMCID: PMC3858967.