Details of the Drug

General Information of Drug (ID: DMML7BE)

Drug Name

Xl147

Synonyms

N-[3-(2,1,3-Benzothiadiazol-5-ylamino)quinoxalin-2-yl]-4-methylbenzenesulfonamide; 956958-53-5; XL147 analogue; PI3K inhibitor X; XL 147; Pilaralisib analogue; N-[3-(2,1,3-benzothiadiazol-5-ylamino)quinoxalin-2-yl]-4-methylbenzenesulfonamide; N-[3-(2,1,3-Benzothiadiazol-5-ylamino)-2-quinoxalinyl]-4-methylbenzenesulfonamide; CHEBI:71957; C21H16N6O2S2; N-(3-(benzo[c][1,2,5]thiadiazol-5-ylamino)quinoxalin-2-yl)-4-methylbenzenesulfonamide; Benzenesulfonamide, N-[3-(2,1,3-benzothiadiazol-5-ylamino)-2-quinoxalinyl]-4-methyl-; 1033110-57-4; PubChem22457; XL-147 derivative 2; cc-43; AC1Q2LO8; AC1LZ6F0; SAR245408 + MSC1936369B

Indication

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

Therapeutic Class

Anticancer Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

448.5

Topological Polar Surface Area (xlogp)

4.2

Rotatable Bond Count (rotbonds)

5

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

9

Chemical Identifiers

Formula: C21H16N6O2S2
IUPAC Name: N-[3-(2,1,3-benzothiadiazol-5-ylamino)quinoxalin-2-yl]-4-methylbenzenesulfonamide
Canonical SMILES: CC1=CC=C(C=C1)S(=O)(=O)NC2=NC3=CC=CC=C3N=C2NC4=CC5=NSN=C5C=C4
InChI: InChI=1S/C21H16N6O2S2/c1-13-6-9-15(10-7-13)31(28,29)27-21-20(23-16-4-2-3-5-17(16)24-21)22-14-8-11-18-19(12-14)26-30-25-18/h2-12H,1H3,(H,22,23)(H,24,27)
InChIKey: MQMKRQLTIWPEDM-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 1893730
ChEBI ID: CHEBI:71957
CAS Number: 1033110-57-4
TTD ID: D03KAC
INTEDE ID: DR1854

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Modulator	[3], [4]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Aldehyde oxidase (AOX1)_{Main DME}	DEAWHS8	AOXA_HUMAN	Substrate	[5]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Solid tumour/cancer

ICD Disease Classification

2A00-2F9Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
PI3-kinase gamma (PIK3CG)	DTT	PIK3CG	1.98E-01	-0.05	-0.55
Aldehyde oxidase (AOX1)	DME	AOX1	3.41E-01	-1.75E-01	-8.17E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7963).
2	Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients with advanced or recurrent endometrial carcinoma. Gynecol Oncol. 2015 Feb;136(2):246-53.
3	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2156).
4	The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models.Mol Cancer Ther.2015 Apr;14(4):931-40.
5	Characterization of aldehyde oxidase enzyme activity in cryopreserved human hepatocytes. Drug Metab Dispos. 2012 Feb;40(2):267-75.
6	Species-specific metabolism of SGX523 by aldehyde oxidase and the toxicological implications. Drug Metab Dispos. 2010 Aug;38(8):1277-85.
7	The critical role of oxidative stress in the toxicity and metabolism of quinoxaline 1,4-di-N-oxides in vitro and in vivo. Drug Metab Rev. 2016 May;48(2):159-82.
8	BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110 and p110 activities in tumor cell lines and xenograft models.Mol Cancer Ther.2013 Nov;12(11):2319-30.
9	PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74.
10	Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
11	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
12	Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies. Clin Cancer Res. 2014 Mar 15;20(6):1656-65.
13	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2155).
14	An integrin-targeted, pan-isoform, phosphoinositide-3 kinase inhibitor, SF1126, has activity against multiple myeloma in vivo.Cancer Chemother Pharmacol.2013 Apr;71(4):867-81.
15	First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1888-95.