Details of the Drug

General Information of Drug (ID: DMNG35S)

• Drug Name: ABT-751
• Synonyms: ABT-751; 141430-65-1; ABT 751; E-7010; ABT751; ABT-751 (E7010); UNII-WDT5V5OB9F; E 7010; WDT5V5OB9F; N-[2-[(4-HYDROXYPHENYL)AMINO]-3-PYRIDYL]-4-METHOXYBENZENESULFONAMIDE; CHEMBL20684; N-(2-((4-Hydroxyphenyl)amino)-3-pyridinyl)-4-methoxybenzenesulfonamide; N-{2-[(4-hydroxyphenyl)amino]pyridin-3-yl}-4-methoxybenzenesulfonamide; Benzenesulfonamide,N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-methoxy-; N-(2-(4-hydroxyphenylamino)pyridin-3-yl)-4-methoxybenzenesulfonamide

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 371.4
  Topological Polar Surface Area (xlogp); 2.8
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 7
• Chemical Identifiers:
  Formula: C18H17N3O4S
  IUPAC Name: N-[2-(4-hydroxyanilino)pyridin-3-yl]-4-methoxybenzenesulfonamide
  Canonical SMILES: COC1=CC=C(C=C1)S(=O)(=O)NC2=C(N=CC=C2)NC3=CC=C(C=C3)O
  InChI: 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)
  InChIKey: URCVCIZFVQDVPM-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 3035714
  ChEBI ID: CHEBI:95043
  CAS Number: 141430-65-1
  DrugBank ID: DB12254
  TTD ID: D09EHO
  INTEDE ID: DR1853

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Modulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Substrate	[3]
Sulfotransferase 1B1 (SULT1B1)	DED5UR3	ST1B1_HUMAN	Substrate	[3]

References

• [1] ClinicalTrials.gov (NCT00436852) ABT-751 in Treating Children With Neuroblastoma That Has Relapsed or Not Responded to Previous Treatment. U.S. National Institutes of Health.
• [2] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [3] 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.
• [4] Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
• [5] Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
• [6] Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
• [7] UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
• [8] Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
• [9] Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
• [10] Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
• [11] Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
• [12] Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
• [13] Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.
• [14] Molecular cloning, expression, and functional characterization of novel mouse sulfotransferases. Biochem Biophys Res Commun. 1998 Jun 29;247(3):681-6.
• [15] Sulfation of benzyl alcohol by the human cytosolic sulfotransferases (SULTs): a systematic analysis. J Appl Toxicol. 2016 Sep;36(9):1090-4.
• [16] Identification of the human SULT enzymes involved in the metabolism of rotigotine. J Clin Pharmacol. 2016 Jun;56(6):754-60.
• [17] Comparison of 2-aminophenol and 4-nitrophenol as in vitro probe substrates for the major human hepatic sulfotransferase, SULT1A1, demonstrates improved selectivity with 2-aminophenol. Biochem Pharmacol. 2007 Jul 15;74(2):352-8.
• [18] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [19] Flubendazole interferes with a wide spectrum of cell homeostatic mechanisms in Echinococcus granulosus protoscoleces. Parasitol Int. 2009 Sep;58(3):270-7.
• [20] Antiproliferating activity of the mitotic inhibitor pironetin against vindesine- and paclitaxel-resistant human small cell lung cancer H69 cells. Anticancer Res. 2007 Mar-Apr;27(2):729-36.
• [21] Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
• [22] NPI-2358 is a tubulin-depolymerizing agent: in-vitro evidence for activity as a tumor vascular-disrupting agent. Anticancer Drugs. 2006 Jan;17(1):25-31.
• [23] Hydrophilic, pro-drug analogues of T138067 are efficacious in controlling tumor growth in vivo and show a decreased ability to cross the blood brain barrier. J Med Chem. 2001 Oct 25;44(22):3599-605.
• [24] Total synthesis and biological evaluation of ustiloxin natural products and two analogs. Bioorg Med Chem Lett. 2006 Sep 15;16(18):4804-7.
• [25] The vascular disrupting agent BNC105 potentiates the efficacy of VEGF and mTOR inhibitors in renal and breast cancer.Cancer Biol Ther.2014;15(11):1552-60.
• [26] National Cancer Institute Drug Dictionary (drug id 598799).