SERABELISIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H17N5O3
Molecular Weight	363.37
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC2=C(O1)C=CC(=C2)C3=CN4C(=CN=C4C=C3)C(=O)N5CCOCC5

InChI

InChIKey=BLGWHBSBBJNKJO-UHFFFAOYSA-N

InChI=1S/C19H17N5O3/c20-19-22-14-9-12(1-3-16(14)27-19)13-2-4-17-21-10-15(24(17)11-13)18(25)23-5-7-26-8-6-23/h1-4,9-11H,5-8H2,(H2,20,22)

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Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23275335
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24915189 | https://www.ncbi.nlm.nih.gov/pubmed/28490463

Serabelisib (INK1117 and TAK-117) is an orally bioavailable, PI3K p110α- isoform-specific inhibitor with an in vitro IC50 of 15 nM, highly selective against other isoforms (p110β, p110γ, and p110δ) and mTOR (no significant inhibitions at 1 μM concentration). It displayed significant efficacy in several PI3Kα mutant-specific preclinical mouse xenograft tumor models, and blocked signaling to Akt and inhibited the growth of cancer cells harboring wild-type or mutated p110α. Preclinical studies showed TAK-117 to have the low potential for disrupting glucose metabolism or for causing cardiac adverse events; in rats and monkeys, doses up to 50 mg/kg/day were well tolerated. Serabelisib is currently under clinical evaluation.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
PI3-kinase p110-alpha subunit 41 Target ID: CHEMBL4005 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23275335	Inhibitor 8297	15.0 nM [IC50]
PI3-kinase p110-beta subunit 31 Target ID: CHEMBL3145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23275335	Inhibitor 8297	4500.0 nM [IC50]
PI3-kinase p110-gamma subunit 32 Target ID: CHEMBL3267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23275335	Inhibitor 8297	1900.0 nM [IC50]
PI3-kinase p110-delta subunit 43 Target ID: CHEMBL3130 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23275335	Inhibitor 8297	13900.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/NCT02393209	Primary	Phase II 1132	Unknown Approved Use Unknown
Renal cell carcinoma 31 Sources: https://clinicaltrials.gov/ct2/show/NCT02724020	Primary	Phase II 1132	Unknown Approved Use Unknown
Endometrial cancer 43 Sources: https://clinicaltrials.gov/ct2/show/NCT02725268	Primary	Phase II 1132	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P000TSN	https://www.1pchem.com/search?query=1P000TSN
AChemBlock	Q65706	http://www.achemblock.com/catalogsearch/result/?q=Q65706
Ambeed	A446445	http://www.ambeed.com/search/Search.html?keyword=A446445
ApexBio Technology	C3103	https://www.apexbt.com/catalogsearch/result/?q=C3103
AstaTech	40557	http://astatechinc.com/CPSResult.php?CRNO=40557
BLD Pharm	BD630078	http://www.bldpharm.com/search/Search.html?keyword=BD630078
Cayman Chemical	19514	http://www.caymanchem.com/app/template/Product.vm/catalog/19514
Chem Scene	CS-5490	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5490
ChemShuttle	157315	https://www.chemshuttle.com/catalogsearch/result/?q=157315
Excenen	EX-A1112	http://www.excenen.com/searchresultlist.php?id=EX-A1112
KeyOrganics	AS-73722	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-73722
Lab Network	LN01350906	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01350906
MedChem Express	HY-12285	https://www.medchemexpress.com/search.html?q=HY-12285&ft=&fa=&fp=
MolPort	MolPort-044-561-595	https://www.molport.com/shop/molecule-link/MolPort-044-561-595
Molnova	M11125	https://www.molnova.com/en/serch-list.html?keywords=M11125
MuseChem	I001074	https://www.musechem.com/product/I001074.html
Selleck Chemicals	S8581	http://www.selleckchem.com/search.html?searchDTO.searchParam=S8581
ShangHai Biochempartner	BCP001086	http://www.biochempartner.com/search_BCP001086
ShangHai Biochempartner	BCP09230	http://www.biochempartner.com/search_BCP09230
TargetMol	T3153	https://www.targetmol.com/search?keyword=T3153
eMolecules	84106207	https://orderbb.emolecules.com/search/#?query=84106207
mcule	MCULE-3430556273	https://mcule.com/MCULE-3430556273/

PubMed

Title	Date	PubMed
A First-in-Human, Phase I, Dose-Escalation Study of TAK-117, a Selective PI3Kα Isoform Inhibitor, in Patients with Advanced Solid Malignancies.	2017 Sep 1	28490463

Patents

Sample Use Guides

In Vivo Use Guide

In total, 24 patients were assigned to once-daily (6 at 100 mg, 6 at 150 mg, 8 at 200 mg, and 4 at 300 mg), 27 to Monday–Wednesday–Friday (MWF) (3 patients each at 200, 300, 400, and 600 mg, 12 at 900 mg, and 3 at 1,200 mg), and 20 to MTuW (3 patients each at 200, 400, and 600 mg, and 11 patients at 900 mg) dosing.

Route of Administration: Oral

In Vitro Use Guide

SK-OV-3 and U87MG cell lines were obtained from ATCC. A total of 5000 cells/well in low serum media (0.2% FBS) were seeded in triplicate wells of a 96-well flat bottom culture plate for 18 h to adhere. Media was aspirated and inhibitors in 0.2% FBS media were added to each well at the indicated concentrations. After 48 h, cell viability was determined using the MTS assay (Cell Titer 96 Aqueous One solution cell proliferation assay kit; Promega) with absorbance (490 nm) measured in a microplate spectrophotometer.

Name

Type

Language

SERABELISIB

Official Name

English

MLN-1117

Code

English

INK-1117

Code

English

serabelisib [INN]

Common Name

English

Serabelisib [WHO-DD]

Common Name

English

AGN-PC-0DB6FL

Code

English

METHANONE, (6-(2-AMINO-5-BENZOXAZOLYL)IMIDAZO(1,2-A)PYRIDIN-3-YL)-4-MORPHOLINYL-

Systematic Name

English

(6-(2-AMINO-5-BENZOXAZOLYL)IMIDAZO(1,2-A)PYRIDIN-3-YL)-4-MORPHOLINYLMETHANONE

Systematic Name

English

INK1117

Code

English

MLN1117

Code

English

TAK-117

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C129825