XL-388

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H22FN3O4S
Molecular Weight	455.502
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(C=CC(=C1F)S(C)(=O)=O)C(=O)N2CCOC3=C(C2)C=C(C=C3)C4=CC=C(N)N=C4

InChI

InChIKey=LNFBAYSBVQBKFR-UHFFFAOYSA-N

InChI=1S/C23H22FN3O4S/c1-14-18(5-7-20(22(14)24)32(2,29)30)23(28)27-9-10-31-19-6-3-15(11-17(19)13-27)16-4-8-21(25)26-12-16/h3-8,11-12H,9-10,13H2,1-2H3,(H2,25,26)

HIDE SMILES / InChI

Description
Sources: http://adisinsight.springer.com/drugs/800019856
Curator's Comment: Description was created based on several sources, including http://mct.aacrjournals.org/content/8/12_Supplement/B146 | https://www.ncbi.nlm.nih.gov/pubmed/23394126

XL388 is a selective small-molecule ATP-competitive inhibitor of mTOR kinase complexes mTORC1 and mTORC2. XL388 inhibited cellular phosphorylation of mTOR complex 1 (p-p70S6K, pS6, and p-4E-BP1) and mTOR complex 2 (pAKT (S473)) substrates. In vitro, XL388 inhibits the viability of solid and hematopoietic tumor cell lines when assayed as a single agent. XL388 also synergizes with chemotherapeutics in cell‐based assays to block cell viability. When dosed orally once daily in mice, XL388 shows robust anti‐tumor activity in multiple xenograft models. Exelixis has discontinued the development of XL388. The company intends to pursue a collaboration partner or other external opportunities for the development of XL388.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mammalian target of Rapamycin (mTORC1) 23 Target ID: CHEMBL2221341 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23394126 \| http://mct.aacrjournals.org/content/8/12_Supplement/B146	Inhibitor 8297		8.0 nM [IC50]
TORC2 complex 3 Target ID: GO:0031932 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23394126 \| http://mct.aacrjournals.org/content/8/12_Supplement/B146	Inhibitor 8297		166.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: http://adisinsight.springer.com/drugs/800019856 http://mct.aacrjournals.org/content/8/12_Supplement/B146	Primary		Preclinical	Unknown Approved Use Unknown
Osteosarcoma 22 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27385099	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

oral administration of XL388 (20 mg/kg body weight, every three days, × 7 times) significantly inhibited U2OS xenograft growth in severe combined immuno-deficient mice.

Route of Administration: Oral

In Vitro Use Guide

XL388 (100 nM) inhibited survival in human osteosarcoma cells

Name

Type

Language

XL-388

Code

English

(7-(6-AMINOPYRIDIN-3-YL)-3,5-DIHYDRO-2H-1,4-BENZOXAZEPIN-4-YL)-(3-FLUORO-2-METHYL-4-METHYLSULFONYLPHENYL)METHANONE

Systematic Name

English

XL388

Code

English

(7-(6-AMINO-3-PYRIDINYL)-2,3-DIHYDRO-1,4-BENZOXAZEPIN-4(5H)-YL)(3-FLUORO-2-METHYL-4-(METHYLSULFONYL)PHENYL)METHANONE

Systematic Name

English

METHANONE, (7-(6-AMINO-3-PYRIDINYL)-2,3-DIHYDRO-1,4-BENZOXAZEPIN-4(5H)-YL)(3-FLUORO-2-METHYL-4-(METHYLSULFONYL)PHENYL)-

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID901336669